CN102753887B - Comprise the system of details in a play not acted out on stage, but told through dialogues indirect illumination equipment, device and method - Google Patents
Comprise the system of details in a play not acted out on stage, but told through dialogues indirect illumination equipment, device and method Download PDFInfo
- Publication number
- CN102753887B CN102753887B CN201180009054.9A CN201180009054A CN102753887B CN 102753887 B CN102753887 B CN 102753887B CN 201180009054 A CN201180009054 A CN 201180009054A CN 102753887 B CN102753887 B CN 102753887B
- Authority
- CN
- China
- Prior art keywords
- electromagnetic energy
- hemozoin
- optical package
- optical
- circuit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000005286 illumination Methods 0.000 title claims description 70
- 201000004792 malaria Diseases 0.000 claims abstract description 114
- 230000003287 optical Effects 0.000 claims description 205
- 230000000638 stimulation Effects 0.000 claims description 128
- 238000001514 detection method Methods 0.000 claims description 109
- 230000005611 electricity Effects 0.000 claims description 18
- 230000000007 visual effect Effects 0.000 claims description 10
- 238000006073 displacement reaction Methods 0.000 claims description 3
- 238000010304 firing Methods 0.000 claims description 2
- 241001416181 Axis axis Species 0.000 claims 1
- PQLMTURQWQZOKE-UHFFFAOYSA-A 3-[18-(2-carboxyethyl)-7,12-bis(ethenyl)-3,8,13,17-tetramethylporphyrin-21,23-diid-2-yl]propanoate;[12-(2-carboxyethyl)-8-(2-carboxylatoethyl)-2,17-bis(ethenyl)-3,7,13,18-tetramethylporphyrin-21-ium-23-id-21-ylidene]iron;iron(5+) Chemical compound [Fe+5].[Fe+5].[Fe+5].[Fe+5].[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC([O-])=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1.[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC([O-])=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1.[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC([O-])=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1.[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC([O-])=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1.[Fe]=[N+]1C(C=C2C(=C(C=C)C(C=C3C(=C(CCC(O)=O)C(=C4)[N-]3)C)=N2)C)=C(C=C)C(C)=C1C=C1C(C)=C(CCC([O-])=O)C4=N1.[Fe]=[N+]1C(C=C2C(=C(C=C)C(C=C3C(=C(CCC(O)=O)C(=C4)[N-]3)C)=N2)C)=C(C=C)C(C)=C1C=C1C(C)=C(CCC([O-])=O)C4=N1.[Fe]=[N+]1C(C=C2C(=C(C=C)C(C=C3C(=C(CCC(O)=O)C(=C4)[N-]3)C)=N2)C)=C(C=C)C(C)=C1C=C1C(C)=C(CCC([O-])=O)C4=N1.[Fe]=[N+]1C(C=C2C(=C(C=C)C(C=C3C(=C(CCC(O)=O)C(=C4)[N-]3)C)=N2)C)=C(C=C)C(C)=C1C=C1C(C)=C(CCC([O-])=O)C4=N1 PQLMTURQWQZOKE-UHFFFAOYSA-A 0.000 abstract description 310
- 108010080417 hemozoin Proteins 0.000 abstract description 310
- 201000009910 diseases by infectious agent Diseases 0.000 abstract description 43
- 238000000034 method Methods 0.000 abstract description 30
- 230000004044 response Effects 0.000 description 296
- 230000005291 magnetic Effects 0.000 description 206
- 239000002105 nanoparticle Substances 0.000 description 168
- 210000001519 tissues Anatomy 0.000 description 103
- 238000009826 distribution Methods 0.000 description 73
- 239000000523 sample Substances 0.000 description 68
- 238000001000 micrograph Methods 0.000 description 61
- 230000002085 persistent Effects 0.000 description 57
- 239000000203 mixture Substances 0.000 description 51
- 241000224016 Plasmodium Species 0.000 description 48
- 210000004027 cells Anatomy 0.000 description 48
- 238000001228 spectrum Methods 0.000 description 42
- 244000079386 endoparasites Species 0.000 description 30
- 210000003743 Erythrocytes Anatomy 0.000 description 25
- 238000003860 storage Methods 0.000 description 25
- 210000000031 Electric organ Anatomy 0.000 description 24
- 230000000694 effects Effects 0.000 description 22
- 235000015220 hamburgers Nutrition 0.000 description 22
- 239000000049 pigment Substances 0.000 description 22
- 230000003595 spectral Effects 0.000 description 22
- 238000003782 apoptosis assay Methods 0.000 description 20
- 230000005522 programmed cell death Effects 0.000 description 20
- 238000003745 diagnosis Methods 0.000 description 19
- 244000045947 parasites Species 0.000 description 18
- 230000000670 limiting Effects 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 14
- 241000223960 Plasmodium falciparum Species 0.000 description 13
- 238000005516 engineering process Methods 0.000 description 12
- 238000000059 patterning Methods 0.000 description 12
- 230000000712 assembly Effects 0.000 description 11
- 230000005670 electromagnetic radiation Effects 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 239000010409 thin film Substances 0.000 description 11
- 230000000078 anti-malarial Effects 0.000 description 10
- 230000009089 cytolysis Effects 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 230000006907 apoptotic process Effects 0.000 description 9
- 230000033228 biological regulation Effects 0.000 description 9
- 238000004891 communication Methods 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 230000002969 morbid Effects 0.000 description 9
- 241000209094 Oryza Species 0.000 description 8
- 235000007164 Oryza sativa Nutrition 0.000 description 8
- 210000003491 Skin Anatomy 0.000 description 8
- 210000003934 Vacuoles Anatomy 0.000 description 8
- 230000001276 controlling effect Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000005284 excitation Effects 0.000 description 8
- 238000011065 in-situ storage Methods 0.000 description 8
- 230000024241 parasitism Effects 0.000 description 8
- 235000009566 rice Nutrition 0.000 description 8
- 230000004936 stimulating Effects 0.000 description 8
- 206010059512 Apoptosis Diseases 0.000 description 7
- 240000004678 Panax pseudoginseng Species 0.000 description 7
- 235000003140 Panax quinquefolius Nutrition 0.000 description 7
- 230000005540 biological transmission Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 235000005035 ginseng Nutrition 0.000 description 7
- 235000008434 ginseng Nutrition 0.000 description 7
- 230000000977 initiatory Effects 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 230000035939 shock Effects 0.000 description 7
- 210000000088 Lip Anatomy 0.000 description 6
- 210000003463 Organelles Anatomy 0.000 description 6
- 208000006551 Parasitic Disease Diseases 0.000 description 6
- 241000209140 Triticum Species 0.000 description 6
- 230000022534 cell killing Effects 0.000 description 6
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 230000001678 irradiating Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000017074 necrotic cell death Effects 0.000 description 6
- -1 nickel metal hydride Chemical class 0.000 description 6
- 230000001105 regulatory Effects 0.000 description 6
- 235000021307 wheat Nutrition 0.000 description 6
- 239000002023 wood Substances 0.000 description 6
- 210000001367 Arteries Anatomy 0.000 description 5
- 210000004369 Blood Anatomy 0.000 description 5
- WHTVZRBIWZFKQO-UHFFFAOYSA-N Chloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 5
- 229960003677 Chloroquine Drugs 0.000 description 5
- 208000009182 Parasitemia Diseases 0.000 description 5
- 210000003462 Veins Anatomy 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000003430 antimalarial agent Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000003990 capacitor Substances 0.000 description 5
- 230000000875 corresponding Effects 0.000 description 5
- 239000004744 fabric Substances 0.000 description 5
- 239000010408 film Substances 0.000 description 5
- 150000003278 haem Chemical class 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000009217 hyperthermia therapy Methods 0.000 description 5
- 230000011218 segmentation Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 5
- 108009000409 Autophagy Proteins 0.000 description 4
- 210000003483 Chromatin Anatomy 0.000 description 4
- 108010077544 Chromatin Proteins 0.000 description 4
- 102000033147 ERVK-25 Human genes 0.000 description 4
- 206010020843 Hyperthermia Diseases 0.000 description 4
- 108090000284 Pepsin A Proteins 0.000 description 4
- 108091005771 Peptidases Proteins 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 230000001640 apoptogenic Effects 0.000 description 4
- 230000006877 autophagy Effects 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 230000001413 cellular Effects 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 230000001808 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 235000019621 digestibility Nutrition 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 239000003365 glass fiber Substances 0.000 description 4
- 230000036031 hyperthermia Effects 0.000 description 4
- 230000002458 infectious Effects 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 230000002934 lysing Effects 0.000 description 4
- 230000005298 paramagnetic Effects 0.000 description 4
- 230000005408 paramagnetism Effects 0.000 description 4
- 229940111202 pepsin Drugs 0.000 description 4
- 239000002096 quantum dot Substances 0.000 description 4
- 229910052904 quartz Inorganic materials 0.000 description 4
- 239000010453 quartz Substances 0.000 description 4
- 230000002285 radioactive Effects 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 210000000601 Blood Cells Anatomy 0.000 description 3
- 210000000170 Cell Membrane Anatomy 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 210000001747 Pupil Anatomy 0.000 description 3
- 230000003213 activating Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000845 anti-microbial Effects 0.000 description 3
- 239000003150 biochemical marker Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
- 229940079593 drugs Drugs 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000001965 increased Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000000051 modifying Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229910052594 sapphire Inorganic materials 0.000 description 3
- 239000010980 sapphire Substances 0.000 description 3
- 210000001563 schizonts Anatomy 0.000 description 3
- 230000001568 sexual Effects 0.000 description 3
- 230000036259 sexual stimuli Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 230000001954 sterilising Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 229920000160 (ribonucleotides)n+m Polymers 0.000 description 2
- 210000004204 Blood Vessels Anatomy 0.000 description 2
- 210000000988 Bone and Bones Anatomy 0.000 description 2
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium Ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 description 2
- 210000003205 Muscles Anatomy 0.000 description 2
- 210000004940 Nucleus Anatomy 0.000 description 2
- 102000014961 Protein Precursors Human genes 0.000 description 2
- 108010078762 Protein Precursors Proteins 0.000 description 2
- 210000001525 Retina Anatomy 0.000 description 2
- 241000282485 Vulpes vulpes Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000003044 adaptive Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000005388 cross polarization Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000005712 crystallization Effects 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 230000005662 electromechanics Effects 0.000 description 2
- 238000004146 energy storage Methods 0.000 description 2
- 230000002708 enhancing Effects 0.000 description 2
- 230000000925 erythroid Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000000446 fuel Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229920000591 gum Polymers 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000002452 interceptive Effects 0.000 description 2
- 230000003834 intracellular Effects 0.000 description 2
- 238000009940 knitting Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229910001416 lithium ion Inorganic materials 0.000 description 2
- 230000005389 magnetism Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000001404 mediated Effects 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 230000005622 photoelectricity Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 238000004382 potting Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000001429 stepping Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000004083 survival Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing Effects 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 238000000015 thermotherapy Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000000577 Adipose Tissue Anatomy 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- BLUAFEHZUWYNDE-NNWCWBAJSA-N Artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 description 1
- 206010003402 Arthropod sting Diseases 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 206010061590 Blood disease Diseases 0.000 description 1
- 210000001124 Body Fluids Anatomy 0.000 description 1
- 101700041333 C1 Proteins 0.000 description 1
- 102000007590 Calpain Human genes 0.000 description 1
- 108010032088 Calpain Proteins 0.000 description 1
- 210000001736 Capillaries Anatomy 0.000 description 1
- 240000002925 Caryocar villosum Species 0.000 description 1
- 206010010254 Concussion Diseases 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 210000000805 Cytoplasm Anatomy 0.000 description 1
- 210000000172 Cytosol Anatomy 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 210000003128 Head Anatomy 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 208000005209 Hematologic Disease Diseases 0.000 description 1
- 210000001624 Hip Anatomy 0.000 description 1
- 210000003284 Horns Anatomy 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 230000005374 Kerr effect Effects 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 241000406668 Loxodonta cyclotis Species 0.000 description 1
- 108020004999 Messenger RNA Proteins 0.000 description 1
- 230000036740 Metabolism Effects 0.000 description 1
- 210000003470 Mitochondria Anatomy 0.000 description 1
- 210000001700 Mitochondrial Membranes Anatomy 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- UNJJBGNPUUVVFQ-ZJUUUORDSA-N Phosphatidylserine Chemical compound CCCC(=O)O[C@H](COC(=O)CC)COP(O)(=O)OC[C@H](N)C(O)=O UNJJBGNPUUVVFQ-ZJUUUORDSA-N 0.000 description 1
- 102000030951 Phosphotransferases Human genes 0.000 description 1
- 108091000081 Phosphotransferases Proteins 0.000 description 1
- 241000223801 Plasmodium knowlesi Species 0.000 description 1
- 241000223810 Plasmodium vivax Species 0.000 description 1
- 210000002435 Tendons Anatomy 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 210000001215 Vagina Anatomy 0.000 description 1
- 101710002785 WIGBRp0010 Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 229930002945 all-trans-retinaldehyde Natural products 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000844 anti-bacterial Effects 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- 229960004191 artemisinin Drugs 0.000 description 1
- 230000001580 bacterial Effects 0.000 description 1
- 244000052616 bacterial pathogens Species 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 230000002759 chromosomal Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005824 corn Nutrition 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 238000010192 crystallographic characterization Methods 0.000 description 1
- 230000001086 cytosolic Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000004059 degradation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 201000002138 hematopoietic system disease Diseases 0.000 description 1
- 108010051269 heme polymerase Proteins 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000004301 light adaptation Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 210000004962 mammalian cells Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920002106 messenger RNA Polymers 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000035786 metabolism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organs Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000002093 peripheral Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000000090 phagocyte Effects 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 238000000513 principal component analysis Methods 0.000 description 1
- 230000000770 pro-inflamatory Effects 0.000 description 1
- 230000001737 promoting Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reduced Effects 0.000 description 1
- 101700030147 rep Proteins 0.000 description 1
- 101700021040 repB Proteins 0.000 description 1
- 101710002782 repF Proteins 0.000 description 1
- 230000003252 repetitive Effects 0.000 description 1
- 230000001718 repressive Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting Effects 0.000 description 1
- 230000002207 retinal Effects 0.000 description 1
- 235000020945 retinal Nutrition 0.000 description 1
- 239000011604 retinal Substances 0.000 description 1
- 239000002965 rope Substances 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000005315 stained glass Substances 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 230000000576 supplementary Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000005619 thermoelectricity Effects 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 210000003812 trophozoites Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
Abstract
The present invention describes for providing a kind of monitor or the system of processing means, device and method, and this monitor or processing means are configured to such as detect hemozoin and monitoring or process malaria infection.
Description
Cross-Reference to Related Applications
Related application and any and all previous generation (parent) of related application, upper two generations (grandparent), on
All themes of the application of three generations (great-grandparent) etc. are to be incorporated herein by reference at this, as long as
These themes do not exist inconsistent with this.
Related application
For the purpose of the non-legal requirements of USPTO, the application constitute Michael C sea lattice (MICHAEL C.HEGG),
Horse repaiies P Huo Ning (MATTHEW P.HORNING), about fourth T Kai Er (JORDIN T.KARE), interior gloomy P wheat Wal
Moral (NATHAN P.MYHRVOLD), Clarens T spy Green (CLARENCE T.TEGREENE), Benjamin's K prestige
Er Xun (BENJAMIN K.WILSON), little Lip river Weir L Wood (LOWELL L.WOOD, JR.) as inventor 2010
Submit on February 10, entitled " comprise the system of multiple-harmonic optical detection to hemozoin nanoparticle, device and
Method (SYSTEMS, DEVICES, AND METHODS INCLUDING MULTI-HARMONIC OPTICAL DETECTION
OF HEMOZOIN NANOPARTICLES) " the part continuation application of 12/658, No. 619 U.S. Patent applications, this U.S. is special
Profit application is currently at co-pending, or its current co-pending application can obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitutes Michael C sea lattice, horse repaiies P Huo Ning, about
Fourth T Kai Er, interior gloomy P wheat Wald, Clarens T spy Green, Benjamin's K Wilson's, little Lip river prestige
Your L Wood as inventor on February 10th, 2010 submit to entitled " comprise the increasing to hemozoin nanoparticle
The system of strong type dark field detection, device and method (SYSTEMS, DEVICES, AND METHODS INCLUDING
ENHANCED DARK FIELD DETECTION OF HEMOZOIN NANOPARTICLES) " No. 12/658,580 U.S. special
The part continuation application of profit application, this U.S. Patent application is currently at co-pending, or its current co-pending application can
To obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitutes Michael C sea lattice, horse repaiies P Huo Ning, about
Fourth T Kai Er, interior gloomy P wheat Wald, Clarens T spy Green, Benjamin's K Wilson's, little Lip river prestige
Your L Wood as inventor in entitled " comprising in response to the existence to hemozoin of submitting on February 10th, 2010
The asymmetric nanoparticle of hemozoin that carries out of multiple-harmonic optical detection paramagnetism vibration, rotate and translate be
System, device and method (SYSTEMS, DEVICES, AND METHODS INCLUDING PARAMAGNETIC
OSCILLATION,ROTATION AND TRANSLATION OF HEMOZOIN ASYMMETRIC NANOPARTICLES IN
RESPONSE TO MULTI-HARMONIC OPTICAL DETECTION OF THE PRESENCE OF HEMOZOIN) "
The part continuation application of 12/658, No. 617 U.S. Patent application, this U.S. Patent application is currently at co-pending, or its
Current co-pending application can obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitutes Michael C sea lattice, horse repaiies P Huo Ning, about
Fourth T Kai Er, interior gloomy P wheat Wald, Clarens T spy Green, Benjamin's K Wilson's, little Lip river prestige
Your L Wood as inventor in entitled " comprising in response to the existence to hemozoin of submitting on February 10th, 2010
Multiple-harmonic optical detection carry out the asymmetric nanoparticle of hemozoin paramagnetism vibration, rotate and translate system,
Device and method (SYSTEMS, DEVICES, AND METHODS INCLUDING PARAMAGNETIC OSCILLATION,
ROTATION AND TRANSLATION OF HEMOZOIN ASYMMETRIC NANOPARTICLES IN RESPONSE TO
MULTI-HARMONIC OPTICAL DETECTION OF THE PRESENCE OF HEMOZOIN) " No. 12/658,638
The part continuation application of U.S. Patent application, this U.S. Patent application is currently at co-pending, or it is the most co-pending
Application can obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitutes Michael C sea lattice, horse repaiies P Huo Ning, about
Fourth T Kai Er, interior gloomy P wheat Wald, Clarens T spy Green, Benjamin's K Wilson's, little Lip river prestige
Your L Wood as inventor in entitled " comprising in response to the existence to hemozoin of submitting on February 10th, 2010
Dark field detection or Lay because of Burger detection carry out the asymmetric nanoparticle of hemozoin paramagnetism vibration, rotate and translate
System, device and method (SYSTEMS, DEVICES, AND METHODS INCLUDING PARAMAGNETIC
OSCILLATION,ROTATION,AND TRANSLATION OF HEMOZOIN ASYMMETRIC NANOPARTICLES IN
RESPONSE TO DARK-FIELD OR RHEINBERG DETECTION OF THE PRESENCE OF HEMOZOIN) "
The part continuation application of 12/658, No. 589 U.S. Patent application, this U.S. Patent application is currently at co-pending, or its
Current co-pending application can obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitutes Michael C sea lattice, horse repaiies P Huo Ning, about
Fourth T Kai Er, interior gloomy P wheat Wald, Clarens T spy Green, Benjamin's K Wilson's, little Lip river prestige
Your L Wood is entitled " for via the plasmodium color in biological tissue submit on February 10th, 2010 as inventor
Element nanoparticle causes system, device and method (SYSTEMS, DEVICES, the AND METHODS that ultraviolet energy produces
FOR INDUCING ULTRAVIOLET ENERGY GENERATION VIA HEMOZOIN NANOPARTICLES IN A
BIOLOGICAL TISSUE) " the part continuation application of 12/658, No. 607 U.S. Patent applications, this U.S. Patent application is worked as
Before be in co-pending, or its current co-pending application can obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitutes horse and repaiies R Belém moral (MATTHEW
R.BEHREND), Michael C sea lattice, horse repaiied P Huo Ning, Benjamin's K Wilson's as inventor in 2010
Submitted to October 25 entitled " comprise the system of details in a play not acted out on stage, but told through dialogues indirect illumination equipment, device and method (SYSTEMS, DEVICES,
AND METHODS INCLUDING A DARK-FIELD REFLECTED-ILLUMINATION APPARATUS) " 12/
The part continuation application of 925, No. 653 U.S. Patent applications, this U.S. Patent application is currently at co-pending, or it is current
Co-pending application can obtain the application of applying date rights and interests.
For the purpose of the non-legal requirements of USPTO, the application constitute horse repair R Belém moral, Michael C sea lattice,
It is entitled " for malaria submit on October 25th, 2010 as inventor that horse repaiies P Huo Ning, Benjamin's K Wilson's
System, device and method (SYSTEMS, DEVICES, the AND METHODS FOR DETECTION OF of disease detection
MALARIA) 12/925 ", the part continuation application of No. 650 U.S. Patent applications, this U.S. Patent application is currently at jointly
Co-pending, or its current co-pending application can obtain the application of applying date rights and interests.
USPTO has disclosed a statement, and its effect is that the computer program of USPTO requires that patent applicant not only to carry
And serial number, and to point out whether apply for is continue case or part continuation application.Peaceful (the Stephen of Shi Difen G elder brother
G.Kunin) " rights and interests (Benefit of the application previously submitted to delivered in USPTO official gazette on March 18th, 2003
Of Prior-Filed Application) " can behttp://www.uspto.gov/web/offices/corn/sol/ og/2003/weekl1/patbene.htmObtain.The present patent application individual human (hereinafter referred to as " applicant ") having been provided above
To specifically mentioning of the application claimed priority according to decree.Applicant understands, and this decree at it with specific reference on language is
Clear and definite, and need not serial number or such as any characterization such as " continue case " or " part continuation application " carrys out requirement to the U.S.
The priority of patent application.While it is true, applicant recognizes, the computer program of USPTO has some data entry requirement,
Therefore the application is appointed as the part continuation application of multiple higher levels application of the application as stated by applicant, but clearly
Point out, these are specified and are not construed in any way as about whether the application contains in addition to theme of its female generation application
There is any kind of annotation of any new theme and/or recognize.
Technical field
The application relates to details in a play not acted out on stage, but told through dialogues indirect illumination equipment and the system, device and the method that comprise this equipment.
General introduction
In an aspect, the present invention is in particular for a kind of equipment, and this equipment comprises a dark ground illuminator.At one
In embodiment, this dark ground illuminator comprises multiple sensor, multiple inquires after device and a master defining at least one aperture
Body structure.In one embodiment, the multiple independent sensor in the plurality of sensor is connected to this to operably
Multiple inquire after in device one or more to form one or more sensors-inquire after device pair.For example, an embodiment party
In case, form a sensor-inquire after device and be positioned as only capturing to the sensor of a part and be freely formed this sensor-spy
Ask device and a part is inquired after the electromagnetic energy being scattered of the sample that device is inquired after.In one embodiment, formed
One sensor-inquire after device is positioned an optical path (such as a, light path) to one or more sensors of a part
In, this optical path generally avoids not from the electromagnetic energy of sample scatter, and this sample is by forming these sensors-inquire after
Device a part the plurality of is inquired after in device one or more inquire after.
In one embodiment, these sensors-inquire after device to being configured to from inquired after by dark ground illuminator
Sample acquisition depend on the electromagnetic energy scattered information of angle or depend on the electromagnetic energy scattered information of wavelength at least one
Person.In one embodiment, the plurality of each inquired after in device comprises a waveguide combination part, and this waveguide combination part has
It is configured to be connected to one or more electromagnetic energy waveguides of at least one electromagnetic energy radiator.For example, at one
In embodiment, an electromagnetic energy waveguide guides the electromagnetic energy from the radiation of electromagnetic energy radiator along an optical path
Amount, and this electromagnetic energy is directed on a focal zone of a sample.In one embodiment, the plurality of waveguide group
Electromagnetic energy is focused on this extremely at the one or more angle of incidence relative to an optical package optical axis by component
On at least one focal zone in a few aperture.
In an aspect, present disclosure is in particular for a kind of dark ground illuminator, and this dark ground illuminator comprises multiple inquiring after
Device and multiple sensor, these inquire after device and sensor forms the part of an agent structure of this dark ground illuminator.
In one embodiment, the plurality of each inquired after in device comprises a waveguide combination part, this waveguide combination part have by
It is configured to be connected to one or more electromagnetic energy waveguides of at least one electromagnetic energy radiator.In one embodiment,
The plurality of waveguide combination part is oriented at least one focal zone that electromagnetic energy focuses on a sample.An enforcement
In scheme, electricity that the plurality of sensor is configured to capture the sample that freely this dark ground illuminator is inquired after, that be scattered
Magnetic energy.In one embodiment, the plurality of sensor is configured to from the sample acquisition inquired after by dark ground illuminator
At least one in the electromagnetic energy scattered information depending on angle or the electromagnetic energy scattered information depending on wavelength.
In an aspect, present disclosure comprises in particular for a kind of malaria detection equipment, this malaria detection equipment: one
Optical package, this optical package has a sample side, a detector side and an optical axis passed through；And
One dark ground illuminator, this dark ground illuminator is close to the sample side of this optical package.In one embodiment, this details in a play not acted out on stage, but told through dialogues
Illumination apparatus comprises: multiple waveguide combination parts；One sensor cluster, this sensor cluster comprises and is configured to shine from by this details in a play not acted out on stage, but told through dialogues
One or more sensors of the electromagnetic energy that the sample reception that funerary objects is inquired after is scattered；And one have at least one
The agent structure of aperture, this at least one aperture is directed at along the axis being substantially parallel to an optical axis.
In an aspect, present disclosure is in particular for a kind of dark ground illuminator system, and this system comprises one and inquires after thorn
Excitation circuit and a testing circuit.In one embodiment, this is inquired after stimulation circuit and is configured to an electromagnetic energy
Stimulate and be directed in one or more volume of focus of a sample.In one embodiment, this testing circuit is configured to
Obtain at one or more angle of incidence freely this inquire after a sample that stimulation circuit inquired after, the electromagnetic energy that is scattered
Amount.In one embodiment, testing circuit is configured to obtaining relative at one or more azimuths of an optical axis
Come freely this inquire after a sample that stimulation circuit inquired after, the electromagnetic energy that is scattered.In one embodiment, detection
Circuit be configured to obtain freely this inquire after a sample that stimulation circuit inquired after, the electromagnetic energy that depends on wavelength dissipates
Penetrate information.In one embodiment, this testing circuit comprises one or more detector, and these detectors are configured to one
Obtain freely at individual or multiple visual field and at one or more depths of focus that this inquires after the sample that stimulation circuit is inquired after
, the electromagnetic energy being scattered.
Foregoing general description is merely illustrative, and is not intended to by any way as limiting.Except above-described
Outside illustrative aspect, embodiment and feature, by referenced in schematic and described in detail below will become apparent from other aspect,
Embodiment and feature.
Brief Description Of Drawings
Figure 1A is the perspective view of the system according to an embodiment.
Figure 1B is the plan view from above of a part for a monitor according to an embodiment or processing means, this dress
Put and comprise the power radiation assembly that at least one electromagnetic energy delivering patterning stimulates.
Fig. 2 A is the perspective view of the system for regulating plasmodium parasitism activity according to an embodiment.
Fig. 2 B is the perspective view of the system for monitoring/regulate plasmodium parasitism activity according to an embodiment.
Fig. 3 A is the perspective view of the hemozoin monitoring device according to an embodiment.
Fig. 3 B is the perspective view of the medical diagnosis device according to an embodiment.
Fig. 3 C is the perspective view of the medical diagnosis device according to an embodiment.
Fig. 3 D is the perspective view of the original position hemozoin monitoring device according to an embodiment.
Fig. 3 E is the perspective view of the anti-malarial therapy device according to an embodiment.
Fig. 4 A is the perspective view of an equipment according to an embodiment.
Fig. 4 B is the perspective view of an equipment according to an embodiment.
Fig. 5 is the flow chart of a kind of method according to an embodiment.
Fig. 6 is the flow chart of a kind of method according to an embodiment.
Fig. 7 is the flow chart of a kind of method according to an embodiment.
Fig. 8 is the flow chart of a kind of method according to an embodiment.
Fig. 9 is the flow chart of a kind of method according to an embodiment.
Figure 10 is the flow chart of a kind of method according to an embodiment.
Figure 11 is the flow chart of a kind of method according to an embodiment.
Figure 12 is the flow chart of a kind of method according to an embodiment.
Figure 13 is the flow chart of a kind of method according to an embodiment.
Figure 14 is the flow chart of a kind of method according to an embodiment.
Figure 15 is the flow chart of a kind of method according to an embodiment.
Figure 16 is the flow chart of a kind of method according to an embodiment.
Figure 17 is the flow chart of a kind of method according to an embodiment.
Figure 18 A and 18B show the flow chart of a kind of method according to an embodiment.
Figure 19 is the flow chart of a kind of method according to an embodiment.
Figure 20 is a monitor according to an embodiment or the perspective view of processing means configuration.
Figure 21 A and 21B show according to an embodiment, respective representative, sweep from the z of hemozoin thin film
Retouch and the plan view from above of transversal scanning method.
It is strong that Figure 22 produces (THG) according to the third harmonic of embodiment (1) hemozoin and (2) quartz
The degree drawing to lateral separation.
The third harmonic that Figure 23 A and 23B show according to multiple illustrated embodiments produces (THG) power to exciting merit
The drawing of rate.
Figure 24 is the drawing to fraction power of photomultiplier tube (PMT) electric current according to an embodiment.
Figure 25 is the voxel image according to the hemozoin crystal in the infected erythrocyte of an embodiment.
Figure 26 according to an embodiment, erythrocytic two-dimensional space scanning to infected and uninfection,
Illustrate the intensity peak corresponding to the hemozoin crystal in infected cell.
Figure 27 is the drawing of photomultiplier tube (PMT) Current versus time according to an embodiment.
Figure 28 is that the third harmonic according to an embodiment produces (THG) drawing to signal power.
Figure 29 is that the third harmonic according to an embodiment produces (THG) drawing to the time.
Figure 30 is the drawing to source wavelength of the wavelength detected according to an embodiment.
Figure 31 A is a monitor according to an embodiment or the perspective view of processing means.
Figure 31 B is a monitor or the place of the use external detection (epi-detection) according to an embodiment
The perspective view of reason device.
Figure 32 A produces, according to an embodiment, use third harmonic, a monitor or the process that (THG) detects
The perspective view of device.
Figure 32 B is a monitor or the perspective view of processing means of the use dark field detection according to an embodiment.
Figure 33 is a monitor or the exploded view of processing means of the use dark field detection according to an embodiment.
Figure 34 A is the exploded view of the dark ground illuminator according to an embodiment.
Figure 34 B is the perspective view of the dark ground illuminator according to an embodiment.
Figure 35 is a monitor or the cross-sectional view of processing means of the use dark field detection according to an embodiment.
Figure 36 is the perspective view of the system according to an embodiment.
Figure 37 A and 37B show the flow chart of a kind of method according to an embodiment.
Figure 38 is the schematic diagram of the system according to an embodiment.
Describe in detail
In the following detailed description with reference to accompanying drawing, accompanying drawing forms a part herein.In the drawings, similar symbol is generally marked
Show similar assembly, unless context dictates otherwise.Describe in detail, diagram and claims described in illustrative
Embodiment is not intended to limit.In the case of the spirit or scope without departing from theme presented herein, it is possible to use
Other embodiment, and other change can be made.
One aspect of the present invention comprise for detecting (such as, assess, calculate, evaluate, determine, measure, identify, measure,
Monitor, quantify, resolve, sensing or the like) such as biological specimen (such as, blood in vivo or in vitro, bone
Head, muscle, skin, fatty tissue, body fluid, tendon, organ, chamber or the like) present in the system of factor marker thing, dress
Put and method.Factor marker thing can comprise the label of the existence indicating such as infectious agent.One limiting examples
Comprise and monitor system, device and the method that the doubtful biology infected by malaria original endoparasite is tested on one's own initiative.One non-limit
Property example processed comprises and includes that details in a play not acted out on stage, but told through dialogues or Lay are because of Burger (Rheinberg) detection technique and the system of method, device and method.
Malaria remains one of the most most important infectious disease.World Health Organization (WHO) makes estimation, and the most about one
Half population lives is having the area of certain risk meeting with malaria." world's malaria report for example, with reference to World Health Organization (WHO)
2008 " (WHO: Geneva 9 (2008)).Malaria is the arthropod borne infection caused by the protist of Plasmodium.Can
To infect in the middle of the plasmodium species of the mankind, it is former that example comprises Plasmodium falciparum, Plasmodium knowlesi, malariae, egg type malaria
Worm and Plasmodium vivax.The estimation of 2006 World Health Organization (WHO)s shows, 247,000,000 malaria disease the most about occurs
Example, wherein 230,000,000 is that Plasmodium falciparum causes." world's malaria report for example, with reference to World Health Organization (WHO)
2008 " (WHO: Geneva 10 (2008)).
Primary malaria original endoparasite, as the medium of malaria, produces plasmodium color when being in and being loaded with in the erythrocyte of hematochrome
Element (birefringence heme crystal).Article " hemozoin (the malaria of (Lamikanra) et al. may be drawn for example, with reference to Lay rice
Disease pigment) directly facilitate apoptosis (Hemozoin (Malarial Pigment) Directly of erythroid precursors
Promotes Apoptosis of Erythroid Precursors)”(PLoS ONE 4(12)(2009):e8446.doi:
10.1371/journal.pone.0008446).Hemozoin, as the biomarker of malaria, is the degraded at hematochrome
Period synthesis, and it was found that in erythrocyte in the digestibility food vacuole of malaria original endoparasite.
One aspect of the present invention comprise include hemozoin nanoparticle carries out multiple-harmonic optical detection system,
Device and method.One limiting examples comprises and includes hemozoin nanoparticle is carried out enhancement mode dark field detection
System, device and method.One aspect of the present invention comprises for detecting and process the system of malaria infection, dress on one's own initiative
Put, method and compositions.One limiting examples comprise the system for the erythrocyte by malaria infection being carried out thermal shock,
Device and method.One limiting examples comprises, and examines including the multiple-harmonic optics in response to the existence to hemozoin
Survey and nanoparticle asymmetric to hemozoin carries out paramagnetism concussion, the system, device and the method that rotate and translate.
One limiting examples comprises and includes that the hemozoin nanoparticle via in biological tissue carries out ultraviolet energy generation
System, device and method.
Figure 1A show system 100, wherein can implement one or more methods or technology with the most on one's own initiative detection or
Process malaria infection.In one embodiment, system 100 especially comprises one or more monitor or processing means 102.Prison
Survey the limiting examples of device or processing means 102 comprise hemozoin monitoring device, spectrometer, anti-malaria treatment device,
Malaria retinal diagnosis device, percutaneous diagnostic equipment 102a, ophthalmoscope 102b (such as, use nonlinear optical element, details in a play not acted out on stage, but told through dialogues or
Lay is because of Burger detection configuration, technology and the ophthalmoscope of method), parasitemia detector, malaria detection equipment 102c or class
Like device.
In one embodiment, system 100 especially comprises a power radiation assembly 104, this power radiation assembly 104
It is configured to stimulate with electromagnetic energy inquire after one or more volume of focus.The limiting examples of power radiation assembly 104
Comprise electromagnetic radiation radiator, circuit, electric conductor, cavity resonator, electromechanical assemblies, electro-optical package, laser instrument, quantum dot, swash
Optical diode, light emitting diode (such as, Organic Light Emitting Diode, polymer LED, polymer phosphorescence light-emitting diodes
Pipe, tiny cavity light-emitting diode, efficient LED or similar diode), flashing lamp, incandescent radiator, continuous wave bulb or
Analog.In one embodiment, power radiation assembly 104 comprises at least one two-photon excitation assembly.An enforcement
In scheme, power radiation assembly 104 comprises one or more laser instrument, laser diode and light emitting diode.A reality
Execute in scheme, power radiation assembly 104 comprise one or more quantum dot, Organic Light Emitting Diode, tiny cavity light-emitting diode with
And polymer LED.In one embodiment, power radiation assembly 104 comprises exciplex laser, two poles
At least one in tube pump formula solid-state laser or semiconductor laser.In one embodiment, power radiation assembly 104 wraps
Containing one or more tunable ultrafast laser.In one embodiment, power radiation assembly 104 comprises one or more milli
Picosecond laser.In one embodiment, power radiation assembly 104 comprises one or more Ti: sapphire laser.?
In one embodiment, the power radiation assembly 104 electromagnetic energy through spatial patterned (spatially-patterned) stings
Swash to inquire after at least one volume of focus, this electromagnetic energy stimulate at least there is firstth district and one be different from this first
Secondth district in district.In one embodiment, the power radiation assembly 104 electromagnetic energy stimulation through spatial patterned is inquired after
At least one volume of focus, the stimulation of this electromagnetic energy at least has firstth district and secondth district, the photograph in this secondth district
Bright intensity, power radiation pattern, peak emission wavelength, pulse-on persistent period, pulse-off persistent period or pulse frequency
In at least one be different from this firstth district.In one embodiment, the power radiation assembly 104 arteries and veins through spatial patterned
The electromagnetic energy of punching multiplexing stimulates inquires after at least one volume of focus.In one embodiment, power radiation assembly
104 produce electromagnetic energy that have such as two or more peak emission wavelength, that multiplex stimulates.
In one embodiment, electromagnetic energy radiation assembly 104 is configured to towards biological specimen (such as, tissue, skin
Blood capillary below skin or the like) guide (such as, via one or more waveguides) electromagnetic radiation.If this biological specimen
Infected by malaria original endoparasite, then the hemozoin in these malaria original endoparasites will be a kind of special to playback injection through skin
The optic response of levying property.
In one embodiment, by adjusting the wavelength of the electromagnetic stimulation produced by power radiation assembly 104, can control
The wavelength of the light that system manifests from hemozoin is (i.e., it is possible to control the ripple of the nonlinear optical response that hemozoin manifests
Long).In one embodiment, the one or more peak emission ripples to the electromagnetic stimulation produced by power radiation assembly 104
Length selects, in order to cause the nonlinear optical response of hemozoin to radiate in the wave-length coverage of infringement hereditary material.
In one embodiment, power radiation assembly 104 delivers the electromagnetism of the pulse multiplex multiplexing through spatial patterned
Energy stimulates, and the stimulation of this electromagnetic energy has from about 400 m. gigawatt (GW)s to the peak power of about 8 TW terawatts.An embodiment
In, the electromagnetic energy that power radiation assembly 104 produces through the pulse multiplex multiplexing of spatial patterned stimulates, and this electromagnetic energy stimulates
There is the peak irradiance of less than about 200 m. gigawatt (GW)s/cm^2.In one embodiment, power radiation assembly 104 produces through sky
Between the electromagnetic energy of pulse multiplex multiplexing of patterning stimulate, this electromagnetic energy stimulates have from about 1 milliwatt to about 1 watt average
Power.In one embodiment, power radiation assembly 104 produces the electromagnetic energy of the pulse multiplex multiplexing through spatial patterned
Stimulating, the stimulation of this electromagnetic energy has the one or more peak emission wavelength from about 690 nanometers to about 2000 nanometers.At one
In embodiment, the electromagnetic energy that power radiation assembly 104 produces through the pulse multiplex multiplexing of spatial patterned stimulates, this electromagnetism
Energy stimulation has the resolution [0.61* (peak emission wavelength/numerical aperture)] from about 300 nanometers to about 10 micron.Formed
The power radiation assembly 104 of a part for monitor or processing means 102 can take many forms, configure and geometric graph
Case, comprises the most one-dimensional, two-dimentional or cubical array, includes the pattern of concentric geometry, includes rectangle, pros
Shape, circle, triangle, polygon, any regular or erose pattern or the like, or its any combination.These energy
One or more in amount radiation assembly 104 can have in x-ray, ultraviolet, visible ray, infrared ray, near infrared ray, billion
Peak emission wavelength in conspicuous, microwave or radio spectrum.In one embodiment, power radiation assembly 104 comprises a warp
Patterning energy radioactive source.In one embodiment, power radiation assembly 104 comprises a patterned luminous source.
In one embodiment, power radiation assembly 104 electromagnetic energy of the pulse multiplex multiplexing through spatial patterned
Multiple volume of focus is simultaneously or sequentially inquired after in amount stimulation.In one embodiment, power radiation assembly 104 is with through sky
Between patterning many depths of focus electromagnetic energy stimulate simultaneously or sequentially inquire after multiple volume of focus.
In one embodiment, power radiation assembly 104 delivers an electromagnetic energy to stimulate, and this electromagnetic energy stimulates tool
There are at least one first peak value radioactive wave length and a second peak emission wavelength being different from this first peak value radioactive wave length.
In one embodiment, power radiation assembly 104 comprises at least one first power radiation device and at least one the second energy
Amount radiator, this at least one second power radiation utensil has the peak emission being different from this at least one the first power radiation device
Wavelength.In one embodiment, power radiation assembly 104 simultaneously or sequentially delivers a first pulse electromagnetic energy thorn
Swash and a second pulse electromagnetic energy stimulates, the pulse duration of this second pulse energy stimulation, pulse frequency, pulse
At least one in intensity, pulse ratio or pulse recurrence rate is different from this first pulse electromagnetic energy to stimulate.An enforcement
In scheme, power radiation assembly 104 simultaneously or sequentially delivers a first pulse electromagnetic energy to stimulate and one second
Pulse electromagnetic energy stimulates, and the stimulation of this second pulse electromagnetic energy has Jiao being different from the stimulation of this first pulse electromagnetic energy
Deeply.In one embodiment, power radiation assembly 104 simultaneously or sequentially delivers a first pulse electromagnetic energy stimulates
And a second pulse electromagnetic energy stimulates, this second pulse electromagnetic energy stimulates and has and be different from this first pulse electromagnetic energy
The resolution that amount stimulates.In one embodiment, being configurable at least partially with removable of power radiation assembly 104
The mode of unloading is attached to biological tested biological surface.
In one embodiment, power radiation assembly 104 is configured to deliver the electromagnetic energy through space-focusing stimulates.
In one embodiment, power radiation assembly 104 comprises a lens arra, and this lens arra is configured to pass
Sending multiple spaced apart energy to stimulate, these energy stimulate and have at least one firstth district and at least one the secondth district, and this is the years old
2nd district have the depth of focus being different from this firstth district.In one embodiment, this secondth district has the peak being different from this firstth district
Value radiation wavelength.In one embodiment, this secondth district has the peak irradiance being different from this firstth district.An enforcement
In scheme, in the intensity in this secondth district, frequency, pulse strength, pulse duration, pulse ratio and pulse recurrence rate extremely
Few one is different from the intensity in this firstth district, frequency, pulse strength, pulse duration, pulse ratio and pulse recurrence rate.
In one embodiment, power radiation assembly 104 comprises the polariser of one or more orthogonal (or intersection).An enforcement
In scheme, sensor cluster 440 comprises the polariser of one or more orthogonal (or intersection).
In one embodiment, power radiation assembly 104 comprises multiple alternative electromagnetic energy waveguide activated, this
A little electromagnetic energy waveguides the electromagnetic energy of the pulse multiplex multiplexing through spatial patterned of radiation is stimulated be directed to this at least one
One or more districts of individual volume of focus.In one embodiment, power radiation assembly 104 comprises a details in a play not acted out on stage, but told through dialogues electromagnetic energy
Radiation assembly, is delivered at least one blood vessel in order to a multimode details in a play not acted out on stage, but told through dialogues is inquired after stimulation.
Seeing Figure 1B, in one embodiment, power radiation assembly 104 provides lighting pattern 600, this lighting pattern
600 include at least one first district 202 and second district 204.In one embodiment, the second of lighting pattern 600
Intensity of illumination (the I in district 204n), power radiation pattern, peak emission wavelength (λn), pulse-on persistent period (D(ON)), pulse
Turn off persistent period (D(OFF)) or pulse frequency (vnAt least one in) is different from the first district 202.Power radiation assembly 104 can
To be configured to stimulate the electromagnetic energy through spatial patterned be supplied to the tissue close to monitor or processing means 102
At least partially, this electromagnetic energy stimulate have be in x-ray, ultraviolet, visible ray, infrared ray, near infrared ray, terahertz,
At least one in microwave or radio spectrum or the peak emission wavelength in a combination thereof.In one embodiment, power radiation
Assembly 104 provides the optical energy through spatial patterned to stimulate.In one embodiment, monitor or processing means 102 are outstanding
It comprises the emission source of the light patterned.In one embodiment, the emission source of the light of this patterning by one through sky
Between the energy of patterning stimulate biological tested one or more districts be provided to.
With continued reference to Figure 1A, in one embodiment, system 100 especially comprises circuit 108, and this circuit 108 is configured
For detection (such as, assess, calculate, evaluate, determine, measure, measure, monitor, quantify, resolve, sensing or the like) non-thread
Property optic response (such as, non-linear multiple-harmonic response and in stimulated at least one volume of focus inquired after by electromagnetic energy
The non-linear multiple-harmonic response energy that hemozoin nanoparticle is associated, or the like).In one embodiment, electricity
Road comprises one or more assembly, these assemblies be coupled to each other to operably (such as, couple by correspondence, can be with
Electromagnetic mode, magnetic means, ultrasonic power, optical mode, inductively, electrically, capacitive way couple, or similar side
Formula).In one embodiment, circuit comprises the assembly of one or more long range positioning.In one embodiment, remotely fixed
The assembly of position can couple to operably via radio communication.In one embodiment, the assembly of long range positioning is permissible
Couple to operably via one or more receptors, emitter, transceiver or the like.
In one embodiment, it is (such as, micro-that circuit especially comprises one or more calculating device 402, such as processor
Processor) 404, CPU (CPU) 406, digital signal processor (DSP) 408, special IC (ASIC) 410,
Field programmable gate array (FPGA) 412 or the like or its any combination, and discrete numeral or simulation can be comprised
Component or electronic component or a combination thereof.In one embodiment, circuit especially comprises one or more scene and can compile
Journey gate array 412, these field programmable gate arrays 412 have multiple programmable logic components.In one embodiment, electricity
Road especially comprises one or more special IC, and these special ICs have multiple predefined logic module.?
In one embodiment, at least one calculates device 402 and is connected to one or more power radiation assembly to operably
104.In one embodiment, circuit comprises and simultaneously or sequentially operates of multiple power radiation assembly 104 or many
Individual calculating device 402.In one embodiment, one or more calculating devices 402 be configured to automatically control with one or
At least one waveform characteristic that the delivery that multiple energy stimulate is associated is (such as, when intensity, frequency, pulse strength, pulse persistance
Between, pulse ratio, pulse recurrence rate or similar characteristics).For example, the feature of impulse wave can be that energy stimulates at an arteries and veins
Rush cycle memory time score.This mark is referred to as dutycycle, and be by by pulse turn-on time divided by a pulse
The total time (such as, adding the turn-off time) in cycle calculates turn-on time.In one embodiment, pulse generator
403 are configured to electronically produce multiple pulse period and non-pulse (or inertia) cycle.An embodiment
In, circuit comprises one and calculates device 402, and this calculating device 402 is connected to power radiation assembly 104 to operably, should
Calculate device and be configured to what control was associated with the delivery of the electromagnetic energy stimulation of the pulse multiplex multiplexing through spatial patterned
At least one parameter.
In one embodiment, calculate device 402 to be configured to control and the electricity of the multiplexing through spatial patterned
The delivery system that the delivery that magnetic energy stimulates is associated, spaced apart delivery pattern, spatial modulation, time-modulation, value, space
At least one in pattern configuration or spatial distribution.In one embodiment, calculate device 402 and comprise one or more process
Device 404, these processors 404 are configured to passing of the control electromagnetic energy stimulation with the pulse multiplex multiplexing through spatial patterned
Sending the space illumination modulation being associated, space illumination intensity or space illumination to deliver, one or more in pattern is associated one
Individual or multiple parameters.In one embodiment, calculate device 402 and comprise one or more processor 404, these processors
The pulse frequency that the delivery that 404 are configured to control the electromagnetic energy with the pulse multiplex multiplexing through spatial patterned stimulates is associated
Rate, pulse strength, pulse ratio or the one or more parameters associated by pulse recurrence rate.In one embodiment, calculate
Device 402 comprises one or more processor 404, and these processors 404 are configured to control and the pulse through spatial patterned
The one or more parameters associated by depth of focus distribution that the delivery that the electromagnetic energy of multiplexing stimulates is associated.An enforcement
In scheme, calculating device 402 and comprise one or more processor 404, these processors are connected to energy to operably and put
Penetrate assembly and be configured to the spatial distribution controlling to stimulate through the electromagnetic energy of the pulse multiplex multiplexing of spatial patterned.One
In individual embodiment, system 100 comprises at least one processor 404, and this processor 404 is operable so that storage and at one
The vibration of the hemozoin nanoparticle magnetically sensed in biological tissue, translate and rotate at least one phase
The information of association.In one embodiment, system 100 comprises at least one processor 404, this processor 404 operable with
Make to store with by non-linear multiple-harmonic response message and the reference plasmodium on one or more computer-readable storage mediums
The information that the comparison of pigment response message is associated.
In one embodiment, calculating device 402 and comprise one or more processor 404, these processors 404 are used for
Produce the control signal that is associated with following item: actively control be associated with the magnetic field being applied to biological specimen dutycycle,
At least one in burst frequencies and pulse recurrence rate.In one embodiment, calculate device 402 and comprise one or many
Individual processor 404, these processors are for producing and actively controlling the control signal that field orientation is associated.An embodiment party
In case, calculating device 402 and comprise one or more processor 404, these processors are for producing and actively controlling magnetic field intensity
The control signal being associated.In one embodiment, calculating device 402 and comprise one or more processor 404, these process
Device is for producing and actively controlling the control signal that magnetic field space distribution is associated.In one embodiment, device 402 is calculated
Comprising one or more processor 404, these processors are for producing and actively controlling the control that magnetic field time pattern is associated
Signal.In one embodiment, calculate device 402 comprise one or more processor 404, these processors for produce with
Actively control the control signal that the magnetic field on-time is associated.In one embodiment, calculate device 402 and comprise one
Or multiple processor 404, the control that these processors are associated for the polarization produced with actively control produced magnetic field is believed
Number.
In one embodiment, calculate device 402 and be configured to respond to detected non-linear multiple-harmonic response
Distribution curve and one or more comparisons with reference to hemozoin nonlinear response distribution curves and activating can actively control
Magnetic field producer.In one embodiment, calculate device 402 be configured to respond to sensor detect with in biological specimen
Hemozoin nanoparticle be associated non-linear multiple-harmonic response distribution curve and change magnetic field on-time, magnetic
At least one in field intensity, field frequency or magnetic field.In one embodiment, calculate device 402 to be configured to respond to
Sensor detects the non-linear multiple-harmonic response distribution curve being associated with the hemozoin nanoparticle in biological specimen
And change magnetic field space distribution patterns.In one embodiment, calculate device 402 to be configured to respond to sensor and detect
When the non-linear multiple-harmonic being associated with the hemozoin nanoparticle in biological specimen responds distribution curve and changes magnetic field
Between pattern.
In one embodiment, circuit especially comprises such as storage instruction or one or more memorizeies 414 of data,
Such as, volatile memory (such as, random access memory (RAM) 416, dynamic random access memory (DRAM) or similar
Thing), nonvolatile memory (such as, read only memory (ROM) 418, Electrically Erasable Read Only Memory (EEPROM),
Compact disk read only memory (CD-ROM) or the like), long-time memory or the like.One or more memorizeies 414
Additionally limiting examples comprises Erasable Programmable Read Only Memory EPROM (EPROM), flash memory or the like.This or
Multiple memorizeies 414 can by one or more instruction bus, data/address bus or power bus be connected to such as one or
Multiple calculating devices 402.
In one embodiment, circuit especially comprises one or more data base 422.In one embodiment, number
Comprise with reference to hemozoin spectral response information, with reference to hemozoin nonlinear optical response information and at least according to storehouse 422
One at least one measured in the parameter determined in exploration mode being associated in vivo or in vitro determined.One
In individual embodiment, data base 422 comprises in absorptance data, extinction coefficient data, scattering coefficient data or class likelihood data
At least one.In one embodiment, data base 422 comprises the reference that such as infectious agent marker data etc. is stored
At least one in data or class likelihood data.In one embodiment, data base 422 comprises references object information.At one
In embodiment, data base 422 comprises erythrocyte plot information, by the erythrocyte plot information of malaria infection or plasmodium
At least one in pigment plot information.
In one embodiment, data base 422 comprises the information that the morbid state tested with biology is associated.?
In one embodiment, data base 422 comprises measurement data.In one embodiment, data base 422 comprises cryptography scheme letter
Breath, regulatory compliance scheme information (such as, FDA regulatory compliance scheme information or similar information), regulations operational version information, checking
Scheme information, mandated program information, delivery system scheme information, activation scheme information, encipherment scheme information, deciphering scheme letter
At least one in breath, processing scheme information or similar information.In one embodiment, data base 422 comprises electromagnetic energy
Stimulate and control delivery information, electromagnetic energy radiator controls at least one in information, power control information or similar information.
In one embodiment, system 100 be configured to by with tested at least one characteristic being associated of biology
An associated input compares with the data base 422 of the reference value stored, and is based in part on this and compares and produce
Raw response.In one embodiment, system 100 is configured at least one spy being associated with the existence of hemozoin
Associated by property one input compares with the data base 422 of the reference value stored, and be based in part on this compare and
Produce response.
In one embodiment, system 100 especially comprises circuit 108, and this circuit 108 is configured to detection and passes through electricity consumption
Magnetic energy stimulates the non-linear multiple-harmonic spectral response inquiring after a doubtful biological specimen with hemozoin and obtain.
The behavior of electric field, magnetic field, charge density and electric current density can such as be described by Maxwell equation.
Works " photonic propulsion ultimate principle (Fundamentals of Photonics) " for example, with reference to Sa Lihe (Saleh) et al.
Page 152 to 170 (second edition, 2007).Nonlinear optical phenomena especially comprises those interactions of electromagnetic radiation and material, its
The response of middle material (such as, polarization, power absorption or similar effect) not with variable (such as, the irradiation describing electromagnetic radiation
Degree, electric field intensity, can flow, fundamental wavelength, fundamental frequency or like variable) it is the most proportional that (that is, the amount of response is the most linear
Ground bi-directional scaling).In one embodiment, electromagnetic energy stimulation is delivered to one or more by power radiation assembly 104
The doubtful volume of focus containing hemozoin.Depend on feature and the persistent period of electromagnetic energy, electromagnetic stimulation and one or
The interaction of the hemozoin in multiple volume of focus results in nonlinear optical response, and this is by the spoke such as scattered
Penetrate and detect.
Nonlinear optical phenomena especially comprises second harmonic and produces and (have the double of the fundamental wavelength that radiated by electromagnetic energy source
Overtones band, the generation of light of 1/2nd wavelength), third harmonic produces (has the fundamental wavelength that radiated by electromagnetic energy source
Treble frequency, the generation of light of 1/3rd wavelength), the 4th harmonic wave produces, difference frequency produces, higher harmonics produces, optical parametric is put
Greatly, optical parametric generation, optical parametric vibration, optical rectification, autonomous parameter are changed downwards, summation frequency produces or similar existing
As.The other limiting examples of nonlinear optical phenomena comprises Brillouin (Brillouin) scattering, multiphoton ionization, optics
Ke Er (Kerr) effect, two-photon absorption or similar phenomenon.
The polarization density relationship of the interaction describing electromagnetic radiation and material can be by such as lower linear section and non-thread
The summation of property part approximates (for the most weak field, it is assumed that there is not permanent dipole moment) (for example, with reference to Sa Lihe et al.
Works " photonic propulsion ultimate principle (Fundamentals of Photonics) " page 873 to 935 (second edition, 2007)):
Wherein,
Describe linear single order optical phenomena, comprise absorption and refraction；
Describe second nonlinear phenomenon, comprise electric light rectification, Pockels (Pockels) electrooptic effect and
Second harmonic produces (such as, doubling frequency)；And
Third-order nonlinear optical effect is described, comprise optical rectification, f our-wave mixing that electric field causes, depend on strong
The refractive index of degree, secondary Kerr effect, self-focusing and third harmonic produce (such as, frequency becomes three times).
In one embodiment, the circuit 108 being configured to detect non-linear multiple-harmonic response energy comprises a biography
Sensor assembly 440, this sensor cluster comprises one or more sensor 442.In one embodiment, sensor cluster
440 are configured to the non-linear multi resonant detecting with being stimulated the multiple hemozoin nanoparticles inquired after to be associated by electromagnetic energy
Wave response distribution curve, and be configured to the non-linear multiple-harmonic response distribution curve detected and one or more references
Hemozoin nonlinear response distribution curve compares.In one embodiment, with reference to hemozoin response distribution
It is one or more true in exploration mode that curve comprises that measuring of in vivo or in vitro determining with at least one be associated
Fixed parameter.In one embodiment, the one or more parameter determined in exploration mode comprises threshold level or target
At least one in parameter.In one embodiment, the one or more parameter determined in exploration mode comprises threshold value letter
Breath.
In one embodiment, sensor cluster 440 comprises an optical energy sensor cluster, and this optical energy passes
Sensor assembly is configured to detect inquires after, from by multimode details in a play not acted out on stage, but told through dialogues, multiple plasmodiums that stimulation is inquired after in the presence of a magnetic field
The optical energy of pigment nanoparticle scattering.
In one embodiment, sensor cluster 440 comprises an electromagnetic energy sensor assembly, and this electromagnetic energy passes
Sensor assembly is configured to detect via dark field detection configuration exist in the case of the first electromagnetic energy stimulates and by multimode
Details in a play not acted out on stage, but told through dialogues stimulates the response energy that the hemozoin nanoparticle inquired after is associated.In one embodiment, system 100 is outstanding
It comprises circuit 110, and this circuit is configured to produce multimode details in a play not acted out on stage, but told through dialogues and inquires after stimulation or multimode Lay and inquire after in stimulation extremely because of Burger
Few one.
It practice, dark field detection configuration comprises blocks center electromagnetism along an optical axis on an objective lens component 114
Energy-ray (such as, by darkground stop or opaque article), these rays be typically through and around a sample.Resistance
Gear center electromagnetic energy ray makes only those oblique rays risen with larger angle (i.e., only by the life in volume of focus
The light of thing sample scatter) arrive detector.In one embodiment, dark field detection configuration comprises compound microscope combination
Part, this compound microscope molectron comprises a concentrator systems, and this concentrator systems makes on all azimuths from one
The electromagnetic energy ray that individual focal zone manifests can form the hollow illumination cone of a reversing, and the summit of this cone is positioned at
The center of sample plane.Dark-ground illumination detection technique can be further by by polariser (such as, orthogonal (or intersection) polarization
Device etc.) add illumination apparatus to and detector comes enhancing contrast ratio and selectivity.Detection is limited to make illumination disappear by cross polarization
Except the scattering events of polarization, thus greatly reduce the false positive signal from health tissues and undesired signal.This is right
It is all relevant for imaging in vivo and in vitro and spectroscope detecting system, device and method.
In one embodiment, sensor cluster 440 comprises an electromagnetic energy sensor assembly, and this electromagnetic energy passes
Sensor assembly be configured to via Lay because of Burger detection configuration detect exist first electromagnetic energy stimulate in the case of with by
Multimode details in a play not acted out on stage, but told through dialogues stimulates the response energy that the hemozoin nanoparticle inquired after is associated.It practice, Lay is joined because of Burger detection
Put and be similar to dark field detection configuration, but use darkground stop, opaque article etc. not along an optical axis；Lay is examined because of Burger
It is measured to put and comprises a Lay with at least two different colours because of Burger light filter.In one embodiment, darkground stop
The central area being typically located is a kind of color (such as, green), and external rings (annulus) is that a kind of contrast color is (such as, red
Color).The light (light not being radiated on sample) of unmodified fills background with the uniform light of the color with center circle, and warp
The light (being radiated on sample and through refraction, the light of scattering etc.) of amendment will have the color of outer annulus.
In one embodiment, this electromagnetic energy sensor assembly comprises at least one Lay because of Burger filter.One
In individual embodiment, this electromagnetic energy sensor assembly is configured to detect and stimulates or the second electromagnetism at existence the first electromagnetic energy
The scattering energy that energy is associated with the hemozoin nanoparticle inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation in the case of stimulating.?
In one embodiment, this electromagnetic energy sensor assembly comprises at least one spectrometer.In one embodiment, this electromagnetism
Energy sensor assembly be configured to detect exist first electromagnetic energy stimulate or the second electromagnetic energy stimulate in the case of with
The spectral response that the hemozoin nanoparticle inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation is associated.
In one embodiment, this electromagnetic energy sensor assembly is configured to detect in existence the first electromagnetic energy thorn
Swash or stimulate the hemozoin nanoparticle inquired after to be associated with by multimode details in a play not acted out on stage, but told through dialogues in the case of the stimulation of the second electromagnetic energy
Scattering energy.
In one embodiment, system 100 especially comprises a sensor cluster 440, this sensor cluster comprise to
A few sensor 442, this sensor is configured to detection and is stimulated inquired after a biological tissue extremely by electromagnetic energy
The non-linear multiple-harmonic response energy that hemozoin nanoparticle in a few volume of focus is associated.An embodiment party
In case, system 100 especially comprises one and calculates device 402, and this calculating device is connected to sensor cluster 440 to operably
At least one sensor and this power radiation assembly 104, this calculating device 402 is configured to provide control signal
To a power radiation assembly.
In one embodiment, system 100 especially comprises a power radiation assembly 104, this power radiation assembly 104
The electromagnetic energy being configured to deliver an effective dose stimulates with the multiple hemozoin nanometers extracting in biological tissue
The nonlinear optical response of particle, feature and persistent period that this nonlinear response drawn has be enough to regulate this life
The biological activity of the malaria infection factor in fabric texture.In one embodiment, this nonlinear response drawn comprises
One or more peak emission wavelength from about 175 nanometers to about 650 nanometers.In one embodiment, this is drawn
Nonlinear response comprises the one or more peak emission wavelength from about 250 nanometers to about 270 nanometers.An embodiment
In, this nonlinear response drawn comprises the peak emission wavelength with about 260 nanometers.
In one embodiment, this nonlinear response drawn has feature and persistent period are adequate to bring about
The programmed cell death of one malaria original endoparasite comprising hemozoin nanoparticle.Many eukaryotic cells, comprise
Single-celled organisms, experiencings the programmed cell death of one or more forms.Programmed cell death can be by stimulating
(such as, the unrepairable of cell damaged, infect, hungry, be exposed to ionizing radiation, heat or toxic chemical) or by shifting
Except repressor causes.In response to particular stimulation the death of initial orders sexual cell may represent by organism carry out favourable
Adaptation, and advantage can be brought in organic life cycle.In the case of such as malaria original endoparasite, parasite group
The programmed cell death of one subgroup of body could be for preventing the means of the Deaths of infected host, thus for posting
Infested offer time enough develops and is delivered to another carrier or host (for example, with reference to combining by reference
Arrive Pang Te herein and Bake (Deponte&Becker) works " parasitology trend (Trends Parasitol.) 20:
165-169,2004) ".By contrast, downright bad (necrosis) is defined as because of the extreme physically or chemically infringement to cell
And the uncontrolled cell death brought.Necrosis can be because of mechanical damage, anoxia, the cell lysis of complement-mediated, high temperature
And be exposed to high toxicity reagent and cause.Necrosis more likely causes inflammation due to the catastrophic failure to cell in host
Reaction.
Have been described for various types of programmed cell death, including (but not limited to) apoptosis, autophagy, swollen die, depend on
Rely property cell lysis and class to adjust to die.Apoptotic feature is to cause changing and ultimately resulting in the one of cell death of cellular morphology
Array of biochemical event.The characteristic of the cellular morphology being associated with apoptosis changes including (but not limited to) nuclear foaming
With segmentation, the formation of apoptotic bodies, the change (such as, membrane asymmetry and the loss of attachment) to cell membrane, cellular contraction
With become round, the change of cytoplasmic densitometric, nucleus segmentation, Chromatin condensation, chromosomal DNA segmentation, oxidation stress, protein
(such as, cytochrome c) is discharged into cytosol from mitochondrion, protein is by protease (especially Pepsin) selectivity
Division and the activity of protease self.By contrast, autophagy is a catabolic process, and the component relating to cell self is led to
Cross the degraded that lysozyme means are carried out, be characterised by the formation of bigger vacuole, these vacuoles nucleus destroy before with specific
Sequential digestion falls organelle.Swollen dying is to causing depleted of energy, organelle to expand and the serious DNA damage of cell membrane disruption
Modulated response.Dependency cell lysis is the proinflammatory cytokines apoptotic pathway caused by the Intracellular bacterial in phagocyte, and
It is different from apoptotic anti-inflammatory pathways.Class apoptosis is similar to necrosis in morphology, wherein forms Cytoplasm vacuole and line
Plastochondria expands, and however it is necessary that new RNA and protein synthesis, and this is consistent with procedural biochemical event.For example, with reference to quote
The works of the Duranty, Walter that is incorporated herein in of mode and Ke Zeer (Durand&Coetzer) " bioinformatics was ground with biology
Study carefully (Bioinform.Biol.Insights) 2:101-117,2008 ".
It is similar to apoptotic programmed cell death observe in malaria original endoparasite.For example, Bai Shi
The plasmodial ookinete through cultivating shows the multiple labelling being similar to apoptotic programmed cell death, comprises line grain
The loss of body transmembrane potential, nuclear chromatin condensation, DNA segmentation, Phosphatidylserine shift to the outer surface of cell membrane and similar
In the activity of Pepsin (for example, with reference to my the nurse bar (Arambage) in being incorporated herein by reference et al.
Works " parasite and host (Parasit.Vectors) (2:32,2009) ".Although the genome of malaria original endoparasite seems and lacks
The homologue of mammalian protease enzyme, but other protease comprising unit's Pepsin and calpain may
For as the medium of the programmed cell death caused in malaria original endoparasite (for example, with reference to being incorporated by reference to this
The works " genome research (Genome Res.) (13:601-616,2003) " of the Wu (Wu) in literary composition et al., look into spy (Chat) etc.
The works " molecule biochemistry parasitology (Mol.Biochem.Parasitol) (153:41-47,2007) " of people).
The programmed cell death being similar to autophagy is observed in plasmodium.For example, have S-nitrosoglutathione-
The process of the blood level Plasmodium falciparum of N-acetyl penicilliamine (SNAP), D-82041 DEISENHOFEN and chloroquine inhibits parasite blood
Disease, and cause the form being similar to autophagy with cellular component vacuolization (for example, with reference to being incorporated by reference to this
The works of the Tuo Dinuo (Totino) in literary composition et al. " experimental parasitology (Exp.Parasitol) (118:478-486,
2008)”)。
Programmed cell death can be by thermal shock or rapid be exposed to the temperature higher than organic normal physiologic range
Cause.Hyperthermia therapy between 40 DEG C and 60 DEG C can cause unordered cell metabolism and film function, and
Cell death is caused in the case of many.In general, at a temperature of less than 60 DEG C, hyperthermia more likely initiator sexual cell
Dead without generally causing necrosis.At a temperature of greater than about 60 DEG C, trigger cell and the possibility condensing necrosis of tissue
Property increase.Increase (such as, 3 DEG C) higher than the relatively small temperature of the normal function temperature of cell and can cause programmed cell
Dead.For example, the temperature from 40 DEG C to 47 DEG C can generally depend on reproducible 37 DEG C of cells playing function
Rely the mode trigger cell in time and temperature dead.The temperature of mammalian cell is increased to such as 43 DEG C and can cause thin
The change of born of the same parents' protein expression and the increase of programmed cell death.Work for example, with reference to Suo Muwolu (Somwaru) et al.
Make the works of " andrology periodical (J.Androl.) (25:506-513,2004) ", Stankovic (Stankiewicz) et al.
" biochemistry periodical (J.Biol.Chem.) (280:38729-38739,2005) ", rope add the works " cell of (Sodja) et al.
Scientific Periodicals (J.Cell Sci.) (111:2305-2313,1998) ", the work of Si Teluokeluomo (Setroikromo) et al.
Make " cellular stress and chaperone (Cell Stress Chaperones) (12:320-330,2007) ", Dubinsky
Et al. (Dubinsky) works " AJR (190:191-199,2008) ", works " the international thermotherapy periodical of inner slope gram (Lepock)
(Int.J.Hyperthermia) (19:252-266,2003) ", the works of Luo Diluodi (Roti Roti) " the international thermotherapy phase
Periodical (Int.J.Hyperthermia) 24:3-15,2008 ", Fuchs (Fuchs) et al. is at " application laser medicine (Applied
Laser Medicine) (Han Si-Peter Berlin (Hans-Peter Berlien) edits, Jie Hade J Muller
(Gerhard J.Muller), New York Co., Ltd of Springer Verlag (Springer-Verlag New York,
LLC), 2003 " works " laser status (the The Laser's Position in medical science in the 187-198 page
Medicine) ", during document above is all incorporated herein by reference.
Malaria original endoparasite is also easy to suffer programmed cell death in response to hyperthermia therapy.For example, established
The isolated body of Plasmodium falciparum and the wild isolated body that obtains from malaria patients cannot grow under the cultivation temperature of 40 DEG C,
Wherein schizont represents Chromatin condensation (pyknosis) and Hyposegmentation (the section's watt seeing in being incorporated herein by reference
The works " experimental medicine periodical (J.Exp.Med.) (169:357-361,1989) " of Butterworth base (Kwiatkowski).It has been proposed that
At high temperature significantly inhibiting Plasmodium falciparum growth is the destruction of the later half circulated due to asexual erythrocyte, the most
The schizont of development is particularly susceptible and stands thermal shock.At 40 DEG C, the process to erythrocyte level Plasmodium falciparum also seems initiation parasitism
The Cytoplasm vacuolization of the food vacuole of worm and destruction (works " the parasitology periodical for example, with reference to baud (Porter) et al.
(J.Parasitol.) (94:473-480,2008) ".Plasmodium falciparum is exposed to the temperature of 41 DEG C and lasts and reach less two minutes and can make
Become and the most relatively reduce at the parasite number that ring stage, trophozoite phase and schizont are interim when measuring after 48 hrs
20%, the 70% and 100% (works for example, with reference to the most assorted (Joshi) in being incorporated herein by reference et al.
" FEBS (312:91-94,1992) ").At 41 DEG C, the heating of erythrocyte level Plasmodium falciparum is lasted 2,8 and 16 hours to make to post
Infested survival reduces by 23%, the 66% and 100% (Ou Kelei seeing in being incorporated herein by reference respectively
Et al. (Oakley) works " infection immunity (Infection Immunity) (75:2012-2025,2007) ").In these heat
Survival under the conditions of shake reduces the appearance of " the crisis form " that be also accompanied by parasite and positive tagged deoxynucleotide in situ
The increase with time correlation that transferase mediated dUTP Nick End labelling method (TUNEL) is movable, this is that programmed cell is dead
The mark died.Response to thermal shock is also accompanied by the change of plasmodium gene and protein expression, and this shows to be exposed to high temperature
(such as, 41 DEG C) have caused the organized biography signal pathway related to when promoting programmed cell death to be used as high temperature
Response.For example, mRNA and protein corresponding to Plasmodium falciparum thermal shock protein 70 (PfHSP-70) are in response to 41 DEG C
Thermal shock and raise 7.42 times and 3.7 times respectively.Other parasite protein matter many be in response to hyperthermia carry out upwards or
Regulation downwards, comprises other stress protein matter, DNA reparation/replication protein, histone, RNA process protein, secretes and turn
Fortune protein and various serine/threonine protein matter kinases (see the Ou Kelei in being incorporated herein by reference
Et al. works " infection immunity (75:2012-2025,2007) ").
In some instances, the programmed cell death in plasmodium can draw by being exposed to one or more medicines
Send out.For example, anti-malaria medicaments chloroquine concentrates in plasmodium food vacuole, and hemozoin molecule is entered by chloroquine in this place
Row end-blocking is to prevent the further organic crystallization of heme, and this crystallization can cause the long-pending of the heme in parasite
Tired.It is highly toxic with the chloroquine of heme complexation for malaria original endoparasite, and destroys film function, thus cause
Cell lysis and ultimately cause parasite cell autodigestion.For example, with reference to the Austria in being incorporated herein by reference
The works " science (Science) (214:667-669,1981) " of lucky (Orjih) et al..In another example, with atropic quinoline pair
The infected erythrocytic number that can detect that is reduced 2 to 3 times by processing of erythrocyte level Plasmodium falciparum, is wherein attended by and posts
The loss of infested mitochondrial membrane potential, this is that the mark of programmed cell death (sees in being incorporated herein by reference
Nai Jieluge (Nyajeruga) et al. works " microorganism infect (Microbes Infect.) (8:1560-1568,
2006)”).With S-nitrosoglutathione-N-acetyl penicilliamine (SNAP), erythrocyte level Plasmodium falciparum is processed posting of exception throw
Infested form " crisis form " and DNA degradation, this is also the mark of programmed cell death.Come by various anti-malaria medicaments
Suppression growth of malaria parasites and initiation plasmodium death may be attended by the change of malaria original endoparasite albuminous body.For example, use
The process of Plasmodium falciparum is brought the up regulation of 41 and 38 parasite protein matter (such as, ginseng by arteannuin and chloroquine respectively
See Puli's torr (Prieto) et al. in being incorporated herein by reference works " PLoS ONE, (3:e4098,
2008)”).In one embodiment, system described herein, device or method can with anti-malaria medicaments sequentially or
Simultaneously use, such as to cause the programmed cell death in Plasmodium falciparum.
In one embodiment, the feature of the nonlinear response drawn and persistent period be enough to cause with cell,
The programmed cell death of host cell, the malaria infection factor or the like (such as, apoptosis, with intracellular program as matchmaker
The cell death being situated between or analogue) the cell stress that is associated of initiation, cellularity change (such as, Chromatin condensation, thin
Born of the same parents shrink, DNA (deoxyribonucleic acid) segmentation etc.), the activation of Pepsin gene or analogue.
In one embodiment, the feature of the nonlinear response drawn and persistent period be enough to produce antibacterial energy
Amount.In one embodiment, the hemozoin in a biological tissue (such as, hemozoin in vivo) brings
Ultraviolet radiation non-linear harmonic wave produce may be used for antimicrobial energy radiate plasmodium.Incident electromagnetic energy stimulates can
To be focusing and pulsed, in order to make intensity be increased sufficiently to realize the level that effective harmonic wave produces.A reality
Executing in scheme, duty ratio of time may be at of a sufficiently low level so that the linear energy of incident illumination deposits without compromising on other
Tissue.Process can in vivo (such as, through skin, ophthalmic, through optical fiber etc.) or in vitro (such as, by outward
The blood flow of part device) occur.In one embodiment, electromagnetic energy stimulates the light comprising narrow bandwidth, bright in order to increase spectrum
Degree and therefore increase harmonic wave generation efficiency.In one embodiment, total to increase via multiple pulse delivery power transmission magnetic energies
Output.In one embodiment, the superimposed pulses using phase matched to combine multiple beam/pulses in target site.
In one embodiment, feature and persistent period that the nonlinear response drawn has be enough to produce one
Sterilization energy stimulates, and the stimulation of this sterilization energy has the one or more peak emission wavelength in ultraviolet ray range.At one
In embodiment, feature and persistent period that the nonlinear response drawn has are adequate to bring about being loaded with the malaria infection factor
The programmed cell death of host cell.
In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises one or more
Electromagnetic transducer 442.The limiting examples of electromagnetic transducer 442 comprises to electromagnetic energy that is that receive or that absorb that have can
The calutron of the response of detection.Electromagnetic transducer can comprise antenna (such as, wire/loop antenna, horn antenna, reflection
Device antenna, chip aerial, phased-array antenna or similar antenna), solid-state photo detector (such as, photodiode, electric charge coupling
Locking device and photoresistor), vacuum photoelectric detector (such as, photocell and photomultiplier), chemical light electro-detection
Device (such as, photographic emulsion), low temperature photoelectric detector (such as, bolometer), luminescence generated by light detector (such as, phosphorescence
Body powder or fluorescent dye/label), MEMS (MEMS) detector (such as, there is electromagnetic response material or element
Micro-cantilever array), or operable to detect and/or other device any of conversion electromagnetic energy.
In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises one or more
Sensor 442, in order to detect the non-linear sound being stimulated the one or more hemozoin nanoparticles inquired after by electromagnetic energy
Answer distribution curve.The limiting examples of sensor 442 comprise electric charge coupling arrangement, cmos device,
Photodiode image sensor device or Whispering-gallery-mode microcavity device.
In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises time integral light
Learn at least one in assembly, linear session integrated component, nonlinear optical component or time auto-correlation assembly.An enforcement
In scheme, comprise one or more one-dimensional, two-dimentional or three-dimensional photoelectricity in order to detect the circuit 108 of non-linear multiple-harmonic response energy
Diode array.In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises one or many
Individual sensor 442, for detecting the non-linear of one or more hemozoin nanoparticles at least one volume of focus
Response distribution curve.In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises at least one
Individual charge coupled device, for detecting the nonlinear response of the multiple hemozoin nanoparticles at least one volume of focus
Distribution curve.In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises at least one point
Photometry, this spectrometer is configured to detect the nonlinear optical of the multiple hemozoin nanoparticles at least one volume of focus
Spectrum response distribution curve.In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises at least
One UV-visible (UV-VIS) diode array detector, for detecting the multiple malarias at least one volume of focus
The nonlinear response distribution curve of protozoon pigment nanoparticle.In one embodiment, in order to detect non-linear multiple-harmonic sound
Should be able to circuit 108 comprise at least one high sensitivity UV-visible (UV-VIS) diode array detector, be used for
Detect the nonlinear response distribution curve of multiple hemozoin nanoparticles at least one volume of focus.An enforcement
In scheme, comprise to be configured to detect radiate in a percutaneous manner in order to detect the circuit 108 of non-linear multiple-harmonic response energy
The circuit of multiple-harmonic photo response (nonlinear optical response such as, electromagnetic energy stimulated).
In one embodiment, in order to detect the circuit 108 of non-linear multiple-harmonic response energy, comprise can be right at one
Should the sensor 442 of the tuple more than of operation at the wavelength of many tuples (multiplet) or wavelength band, i.e. can be at first wave
The first sensor of operation, the second sensor that can operate at second wave length/wavelength band etc. at length/wavelength band.At one
In embodiment, comprise sensor 442 or the many tuples of sensor in order to detect the circuit 108 of non-linear multiple-harmonic response energy
Focal plane arrays (FPA) (such as, Baeyer (Bayer) or Foveon sensor).
In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises a sensor
Assembly 440, in order to detect and to be stimulated in a biological tissue in the multiple volume of focus inquired after by pulse electromagnetic energy many
The non-linear multiple-harmonic response distribution curve that individual hemozoin nanoparticle is associated.In one embodiment, in order to examine
The circuit 108 surveying non-linear multiple-harmonic response energy comprises at least one sensor 442, stimulates with by electromagnetic energy for detection
(such as, pulse electromagnetic energy stimulates, through the electromagnetic energy stimulation of spatial patterned, the stimulation of multiplexed electromagnetic energy, warp
The electromagnetic energy of the pulse multiplex multiplexing of spatial patterned stimulates, through the electromagnetic energy stimulation or the like of time patterning) draw
The non-linear multiple-harmonic that at least one in the second harmonic response, third harmonic response or the 4th harmonic response that go out is associated rings
Should be able to.
In one embodiment, the circuit 108 responding energy in order to detect non-linear multiple-harmonic comprises an optics group
Component 112 and at least one sensor 442, for collecting via collected outside (epi-collection) pattern and detect
Second harmonic response, the third harmonic response or the drawn is stimulated by the electromagnetic energy of the pulse multiplex multiplexing through spatial patterned
At least one in four harmonic responses.Optical package 112 can take various shape and configuration.In one embodiment,
(such as, optical package 112 comprises one or more lens, optical element (such as, beam splitter and lens), diffraction element
Fresnel (Fresnel) lens), light filter, polariser or the like, in order to from source (such as, a power radiation assembly
104, nonlinear optical response or the like) electromagnetic radiation guide and shape.In one embodiment, dark-ground illumination
Detection technique can be further by adding the polariser of orthogonal (or intersect) to illumination apparatus and detector carrys out enhancing contrast ratio
And selectivity.Detection is limited to the scattering events making illumination eliminate polarization by cross polarization, thus greatly reduces from healthy group
The false positive signal knitted and undesired signal.This detects system for imaging in vivo and in vitro and spectroscope
It is all relevant for system, device and method.
The limiting examples of lens comprises cylindrical gradient index (GRIN) lens, doublet lens or triple lens,
Electromagnetic radiation from a source (such as, power radiation assembly 104, nonlinear optical response or the like) is entered by these lens
Row is collected and shapes.In the case of electromagnetic radiation source comprises the multiple optical fiber feeding one or more lens, these
Lens are optionally joined to these optical fiber or integrated with these optical fiber.
In one embodiment, optical package 112 comprises polarization sensitive material, chromatic aberration correction or other optical technology
In one or more, for controlling the shape of electromagnetic radiation, phase place, polarization or other characteristic.In one embodiment,
Optical package 112 comprise one or more polariser, color filter, exit pupil extender, chromatic aberration correcting element, eye follow the tracks of unit
Part and foreground mask, these elements can be incorporated into wherein for application-specific in due course.In one embodiment,
Optical package 112 comprises at least one Lay because of Burger light filter.In one embodiment, optical package 112 comprises one
Individual objective lens component 114, this objective lens component has the alternative numerical aperture controlled from about 0.5 to about 1.4.At one
In embodiment, the circuit 108 being configured to detect non-linear multiple-harmonic response energy comprises a calculating device 402, is used for
Actively control the numerical aperture of the objective lens component 114 with the alternative numerical aperture controlled from about 0.5 to about 1.4
Footpath.In one embodiment, system 100 comprises the objective lens component 114 with the numerical aperture from about 0.5 to about 1.4.
In one embodiment, optical package 112 receives of the radiation being scattered with dark field collection configuration
Point.In one embodiment, optical package 112 is collected configuration with Lay because of Burger and is received one of the radiation being scattered
Point.In one embodiment, optical package 112 receives a part for the radiation being scattered with collected outside configuration.?
In one embodiment, in order to detect non-linear multiple-harmonic response energy circuit 108 comprise be configured to detect in position with
Stimulated the multiple malarias at least one volume of focus inquired after former by the electromagnetic energy of the pulse multiplex multiplexing through spatial patterned
The circuit of the non-linear multiple-harmonic response energy that worm pigment nanoparticle is associated.
In one embodiment, system 100 especially comprises circuit 116, this circuit 116 in order to by with the non-thread detected
Property multiple-harmonic the response message information being associated and the reference information being configured as data structure 424 compare.At one
In embodiment, system 100 especially comprises circuit 116, and this circuit is configured to respond with the non-linear multiple-harmonic detected
The information that information is associated and the reference hemozoin response message being configured as data structure 424 compare.One
In individual embodiment, data structure 424 comprises one or more exploration (heuristics).In one embodiment, this
Individual or multiple probe packet are used for determining the change associated by least one physical parameter being associated with a kind of biofluid containing one
The exploration of rate.In one embodiment, the one or more probe packet is used for determining hemozoin nanoparticle containing one
The exploration of the existence of son.In one embodiment, the one or more probe packet is used for determining depositing of infectious agent containing one
Exploration.In one embodiment, the one or more probe packet is used for determining an infected tissue district containing one
The exploration of at least one dimension.In one embodiment, the one or more probe packet is containing a position being used for determining infection
The exploration put.In one embodiment, the one or more probe packet is used for determining and the one or more focusing containing one
The exploration of the rate of change that a biochemical marker in volume is associated.
In one embodiment, the one or more probe packet is used for determining biochemical marker aggregation rate containing one
The exploration of (such as, hemozoin aggregation rate, hemozoin polymer aggregational speed or similar aggregation rate).At one
In embodiment, the one or more probe packet is containing an exploration being used for determining the type of biochemical marker.An enforcement
In scheme, the one or more probe packet containing one for producing erythrocyte plot information, bent by the erythrocyte of malaria infection
The exploration of at least one in line chart information or hemozoin plot information.
In one embodiment, the one or more probe packet is containing an examination being used for producing at least one initial parameter
Visit.In one embodiment, the one or more probe packet is used for forming one from one or more initial parameters containing one
The exploration of initial parameter set.In one embodiment, the one or more probe packet is used for producing at least one containing one
Initial parameter and the exploration from one the initial parameter set of formation of this at least one initial parameter.In one embodiment,
The one or more probe packet contains at least one pattern classification and regression scheme.
In one embodiment, at least one data structure 424 comprises and hemozoin nonlinear optical phenomena light
The information associated by least one parameter that spectrum information is associated.For example, in one embodiment, data structure 424
Comprise and hemozoin second harmonic response spectrum information, hemozoin third harmonic response spectrum information or plasmodium color
The information associated by least one parameter that at least one in element the 4th harmonic response spectral information is associated.An enforcement
In scheme, data structure 424 comprises references object information.In one embodiment, data structure 424 comprises erythrocyte curve
Figure information, by least one in the erythrocyte plot information of malaria infection or hemozoin plot information.
In one embodiment, system 100 especially comprises one or more computer-readable media driver 426, connects
Mouth socket, USB (universal serial bus) (USB) port, memory card slot or the like, and one or more input/output assembly
428, such as graphical user interface 430, display, keyboard 432, keypad, trace ball, stick, touch screen, mouse, switch,
Dial or the like, and other peripheral unit any.In one embodiment, system 100 comprises one or more use
Family input/output assembly 428, these user's input/output assemblies are connected at least one to operably and calculate device 402
With control (electricity, dynamo-electric, software enforcement, firmware enforcement or other control, or a combination thereof) and the one or more power radiation group
At least one parameter associated by energy delivery that part 104 is associated.In one embodiment, system 100 especially comprises one
Individual or multiple modules, these modules the most operable for be configured to trunk subscriber output and/or input one
Or multiple input/output assembly 428 communicates.In one embodiment, a module comprises electric, electromechanics, software enforcement
, firmware implement or other control device one or more examples.This device comprises one or more realities of following device
Example: memorizer 414, calculating device 402, port, valve 132, antenna, power supply or other supply；Logic module or other signaling
Module；Scale or other this type of active or passive detection assembly；Or piezoelectric transducer, shape memory member, MEMS
(MEMS) element or other actuator.
Computer-readable media driver 426 or memory bank can be configured to accept signal bearing media (such as,
Computer-readable storage medium, computer-readable recording medium or the like).In one embodiment, it is used for making system 100
The program of any one in method disclosed by execution can be stored in such as computer-readable recording medium (CRMM) 434, letter
On number carrying media or the like.The limiting examples of signal bearing media comprises recordable-type media, such as tape, soft magnetism
Dish, hard disk drive, compact disk (CD), digital video disk (DVD), Blu-ray Disc, digital magnetic tape, computer storage
Or the like, and transmission type media, such as numeral and/or (such as, fiber optic cables, waveguide, the wire communication of analogue communication media
Link, wireless communication link (such as, emitter, receptor, transceiver, transmitting logic, reception logic etc.) etc.).Signal
The other limiting examples of carrying media is including (but not limited to) DVD-ROM, DVD-RAM, DVD+RW, DVD-RW, DVD-
R, DVD+R, CD-ROM, super-audio CD, CD-R, CD+R, CD+RW, CD-RW, video compact disc, super video compact disc, fast
Flash memory, tape, magneto-optic disk, minidisk (MINIDISC), non-volatile memory card, EEPROM, CD, optical storage
Device, RAM, ROM, system storage, webserver or the like.
In one embodiment, system 100 comprise in one or more logic devices (such as, programmable logic device,
Complex Programmable Logic device, field programmable gate array, special IC or the like) the signaling bearer matchmaker of form
Body, these logic devices include the data structure 424 such as comprising one or more look-up table.In one embodiment, it is
System 100 especially comprises the signaling bearer matchmaker with the reference hemozoin nonlinear response information being configured to data structure 424
Body.In one embodiment, data structure 424 comprises malaria infection instruction information, hemozoin spectral information, plasmodium
At least one in pigment spectral response information, morbid state instruction information or diseased tissue instruction information.
System 100 can especially comprise one or more receptor 1206, transceiver 1208, emitter 1210 or similar
Thing.In one embodiment, at least one in the one or more receptor 1206, transceiver 1208 or emitter 1210
Wirelessly being connected to one and calculate device 402, this calculating device 402 is via the control unit of radio communication Yu system 100
Communication.In one embodiment, at least one receptor 1206 or transceiver 1208 are configured to obtain and one group of target, life
The information that substance markers thing or the like is associated is for detection.In one embodiment, at least one receptor 1206 or
Transceiver 1208 is configured to obtain the information being associated with one group of physiological property for detection.In one embodiment,
At least one receptor 1206 or transceiver 1208 be configured to obtain the information that is associated with one or more physiological propertys with
For detecting.In one embodiment, at least one receptor 1206 or transceiver 1208 be configured to obtain with one or
The information that multiple hemozoin characteristics are associated is for detection.
In one embodiment, system 100 comprises at least one transceiver 1208, and this transceiver 1208 is configured to ring
Should compare in this and carry out reporting state information with multiple time intervals.In one embodiment, system 100 comprises at least one
Transceiver 1208, this transceiver 1208 is configured to respond to this and compares and ask to believe with reference to hemozoin nonlinear response
Breath.
In one embodiment, system 100 comprises an emitter, and this emitter is configured to send and detect
The comparison information that non-linear multiple-harmonic response energy is associated with the comparison with reference to hemozoin response distribution curve.At one
In embodiment, at least one in receptor 1206 or transceiver 1208 is configured to acquisition and is associated about tested with biology
The information of target detection set of one or more characteristics.In one embodiment, system 100 comprise emitter 1210,
At least one in receptor 1206 or transceiver 1208, this at least one is configured to obtain by a biological specimen radiation
, because of magnetization cause nonlinear optical response information.In one embodiment, system 100 comprises simultaneously or sequentially
Launch or at least one transceiver 1208 of the information of reception.
In one embodiment, system 100 especially comprises circuit 116, this circuit 116 be configured to by with detect
The information that non-linear multiple-harmonic response energy is associated compares with reference to hemozoin response distribution curve.A reality
Execute in scheme, for the information being associated with the non-linear multiple-harmonic response energy detected is responded with reference to hemozoin
The circuit 116 that distribution curve compares comprises one or more computer-readable storage medium, this computer-readable storage matchmaker
Body has the configuration reference hemozoin response distribution curve as data structure 424, this reference plasmodium response distribution song
Line comprises hemozoin second harmonic response spectrum information, hemozoin third harmonic response spectrum information or plasmodium color
At least one in element the 4th harmonic response spectral information.In one embodiment, with reference to hemozoin response distribution song
Line comprises the reference nonlinear response information of instruction hemozoin nanoparticle aggregation speed.In one embodiment, ginseng
Examine the ginseng of the existence that hemozoin response distribution curve comprises the hematochrome metabolite that instruction comprises heme polymer
Examine nonlinear response information.In one embodiment, comprise with reference to plasmodium color with reference to hemozoin response distribution curve
Element nanoparticle non-linear susceptibility information.
In one embodiment, the non-linear multiple-harmonic response energy being configured to detecting is same with reference to plasmodium color
The circuit 116 that element response distribution curve compares comprises one or more computer-readable storage medium, this computer-readable
Storage media have the configuration reference hemozoin response distribution curve as data structure 424, this reference hemozoin
It is non-linear that response distribution curve comprises hemozoin nonlinear response information, hemozoin spectral information or hemozoin
At least one in susceptibility information.
In one embodiment, it is configured to the non-linear multiple-harmonic response energy detected and reference plasmodium color
The circuit 116 that element response distribution curve compares comprises one or more computer-readable storage medium, this computer-readable
Storage media comprise the executable instruction being stored thereon, these executable instructions indicating gage when performing on a computer
Calculate device 402:(a) the one or more ginsengs being associated with reference to hemozoin nonlinear response information are called from storage device
Number；And (b) performs the comparison of the non-linear multiple-harmonic same one or more parameters called of response distribution curve detected.?
In one embodiment, the one or more computer-readable storage medium comprises performing of being stored thereon further and refers to
Order, these executable instructions indicate calculating device 402 to compare in response to this and determine malaria when performing on a computer
Existence, do not exist or one or more in seriousness.
In one embodiment, it is configured to the non-linear multiple-harmonic response energy detected and reference plasmodium color
The circuit 116 that element response distribution curve compares comprises an emitter, and this emitter is configured to send and examine in position
The comparison information that the non-linear multiple-harmonic response energy measured is associated with the comparison with reference to hemozoin response distribution curve.
In one embodiment, it is configured to divide the non-linear multiple-harmonic response energy detected with reference to hemozoin response
The circuit 116 that cloth curve compares comprises a transceiver 1208, and this transceiver is configured to receive launching plasmodium color
The request of at least one in element reference information, the non-linear multiple-harmonic response energy detected in position and comparison information.
In one embodiment, it is configured to the non-linear multiple-harmonic response energy detected and reference plasmodium color
The circuit 116 that element response distribution curve compares comprises the transceiver being configured to receive hemozoin filtration information
1208.In one embodiment, it is configured to the non-linear multiple-harmonic response energy detected and reference hemozoin
The circuit 116 that response distribution curve compares comprises the electromagnetism being configured to receive the pulse multiplex multiplexing through spatial patterned
Energy stimulates the transceiver 1208 of delivery parameter information.In one embodiment, it is configured to non-linear many by detect
Harmonic response energy and comprising with reference to the hemozoin response circuit 116 that compares of distribution curve be configured to by rule or
Irregular time interval carrys out the transceiver 1208 of reporting state information.In one embodiment, it is configured to detect
Non-linear multiple-harmonic response energy with respond the circuit 116 that compares of distribution curve with reference to hemozoin and comprise and be configured
For storing the circuit of paired and azygous non-linear multiple-harmonic response data.In one embodiment, be configured to by
The non-linear multiple-harmonic response energy detected and the circuit 116 compared with reference to hemozoin response distribution curve comprise
At least one processor, this processor is operable so that same with reference to hemozoin with to non-linear multiple-harmonic response energy
The information that the comparison that response distribution curve is carried out is associated is stored on one or more computer-readable storage medium.
In one embodiment, system 100 especially comprises circuit 120, and this circuit is configured to wirelessly transmit with right
The ratio that the non-linear multiple-harmonic response energy detected is associated with the comparison carried out with reference to hemozoin response distribution curve
Relatively information.In one embodiment, system 100 especially comprises circuit 122, and this circuit is configured to optionally tune through sky
Between patterning pulse multiplex multiplexing electromagnetic energy stimulate Wavelength distribution or the most non-linear collected multiple-harmonic ring
At least one in the Wavelength distribution answered.
In one embodiment, system 100 especially comprises circuit 124, and this circuit is configured to be based at least partially on
The non-linear multiple-harmonic response energy detected with reference to one or more comparing between hemozoin response distribution curve
And produce response.In one embodiment, this respond packet contains visual representation, audio representation (such as, alarm, a tissue area
Audio volume control expression or the like), sense of touch represent or sense of touch represent (such as, sense of touch figure, tactile display, sense of touch curve chart, touch
Feel that interactive depiction, haptic model (such as, multidimensional model in an infected tissue district or the like), tactile patterns are (such as,
Refreshable braille (Braille) display), sense of touch audio frequency show, sense of touch-audio curve figure or the like) at least one
Person.In one embodiment, this respond packet containing produce biological specimen spectral information, tissue spectrum information, fat spectral information,
In muscle spectral information, bone spectral information, blood constituent spectral information, hemozoin spectral information or similar information extremely
At least one during the vision of one, audio frequency, sense of touch or sense of touch represent less.In one embodiment, this respond packet is containing producing
At least one in both below: biological specimen by the probability of malaria infection, or with biological specimen being determined by malaria infection
The level of confidence of probability correlation connection.
In one embodiment, this respond packet is containing producing and tested at least one physics being associated of biology or life
Change at least one during the vision of characteristic, audio frequency, sense of touch or sense of touch represent.In one embodiment, this respond packet is containing producing
At least one physics being associated with parasitic infection, morbid state or the like or the vision of biochemical characteristic, audio frequency, sense of touch or
Sense of touch represent at least one.
In one embodiment, this respond packet is containing initial one or more processing schemes.In one embodiment, should
Comprise the respond packet of initial one or more processing scheme containing at least one disposal system initial.In one embodiment, should
Respond packet stimulates containing delivering an energy.In one embodiment, this respond packet is containing delivering a kind of activating agent.An enforcement
In scheme, this respond packet stimulates and a kind of activating agent containing simultaneously or sequentially delivering an energy.An embodiment
In, this respond packet containing response signal, control signal, at least one in change of processing parameter or the like.
In one embodiment, this respond packet is containing the change to the feature that an electromagnetic energy stimulates.For example, exist
In one embodiment, this respond packet is containing to peak power, peak irradiance, focal spot size, pulse width, peak emission wavelength
The change of at least one in or the like.In one embodiment, this respond packet is containing to electromagnetic energy stimulus intensity, electromagnetism
Energy stimulus frequency, electromagnetic energy boost pulse frequency, electromagnetic energy boost pulse ratio, electromagnetic energy boost pulse intensity,
The change of at least one in electromagnetic energy boost pulse persistent period, electromagnetic energy boost pulse repetitive rate or the like.
In one embodiment, the circuit being configured to be based at least partially on one or more comparison and produce response
124 comprise one or more receptor 1206, emitter 1210, transceiver 1208 or the like.In one embodiment, quilt
It is configured to be based at least partially on one or more comparison and produces the circuit 124 of response and comprise emitter 1210 or transceiver
At least one in 1208, this at least one is configured to send with the non-linear multiple-harmonic response energy detected with reference to malaria
The comparison information that the comparison of protozoon pigment response distribution curve is associated.In one embodiment, it is configured at least partly
Ground produces the circuit 124 of response and comprises at least in receptor 1206 or transceiver 1208 based on one or more comparison
Person, this at least one is configured to obtain with reference to hemozoin response distribution curve information.
In one embodiment, system 100 especially comprises the circuit 126 being configured such that generation magnetic field.Citing comes
Say, in one embodiment, circuit 126 comprise be configured to exist apply to produce in the case of current potential one of magnetic field or
Multiple conductive traces.In one embodiment, it is configured to produce the circuit 126 in magnetic field comprise one and be configured to generation and penetrate
Frequently the radiofrequency launcher of signal.In one embodiment, the circuit 126 being configured to produce magnetic field comprises one and is configured to
Producing the radiofrequency launcher of radiofrequency signal, it is the most right that the feature of this radiofrequency signal and persistent period be enough to
Accurate multiple hemozoin nanoparticles.In one embodiment, the circuit 126 being configured to produce magnetic field comprises to produce
One or more coils of raw one or more radio-frequency pulses.
In one embodiment, system 100 especially comprises the circuit 128 producing magnetic stimulation.An enforcement
In scheme, circuit 128 comprises a radiofrequency launcher being configured to produce radiofrequency signal.In one embodiment, circuit
128 comprise the one or more conductive traces being configured to produce magnetic field in the case of there is applying current potential.An enforcement
In scheme, circuit 128 comprises the one or more coils being configured to produce one or more radio-frequency pulse.An embodiment party
In case, circuit 128 comprises multiple radio-frequency coil.In one embodiment, circuit 128 comprise be configured to produce time-varying magnetic field
Multiple coils.
In one embodiment, feature and the persistent period of produced electromagnetic stimulation be enough to cause a biology
Hemozoin nanoparticle in sample in vivo delivers the hyperthermia therapy that magnetic causes.Because hemozoin nanometer
Particle is paramagnetic, so in one embodiment, applying magnetic field gradient can be to the plasmodium color in malaria original endoparasite
Element applying power.In one embodiment, time-varying magnetic field is applied to hemozoin and can cause hemozoin particle
The movement quickly, somewhat vibrated, and then by hemozoin and therefore parasite is heated；Heat be enough to negatively to affect or
Kill parasite, will not substantially affect the normal function of the cell of uninfection simultaneously.
In one embodiment, system 100 especially comprises circuit 130, and this circuit 130 is configured to detection and there is magnetic
Stimulate or multiplexed Lay is inquired after in stimulation at least because of Burger with being inquired after by multiplexed details in a play not acted out on stage, but told through dialogues in the case of Chang
The scattered information that multiple hemozoin nanoparticles that one is inquired after are associated.
In one embodiment, system 100 especially comprises circuit 128, and this circuit 128 is configured to produce a magnetic field
Stimulating, the feature of this magnetic stimulation and persistent period be enough to cause the hemozoin nanoparticle in a biological specimen to exist
The hyperthermia therapy that vivo Delivery magnetic causes.
In one embodiment, system 100 especially comprises the circuit 132 being configured to dynamically control magnetic stimulation.
In one embodiment, the circuit 132 being configured to dynamically control magnetic stimulation comprises one or more processor 404,
These processors are connected to the circuit 128 being configured to produce electromagnetic stimulation to operably, and are configured to management
The one or more parameters being associated with the delivery to the tested district of biology of the pulsed magnetic sexual stimulus.An embodiment party
In case, the circuit 132 being configured to dynamically control magnetic stimulation comprises one or more processor 404, these processor quilts
It is configured to regulate and produce delivery system parameter, the spaced apart delivery pattern parameter or temporal that electromagnetic stimulation is associated
Deliver at least one in pattern parameter.
In one embodiment, system 100 especially comprise be configured to the scattered information that detects former with reference to malaria
The circuit 134 that worm pigment details in a play not acted out on stage, but told through dialogues scattering data compares.In one embodiment, the non-linear multiple-harmonic of comparison it is configured to
The circuit 134 of response energy distribution curve comprises one or more computer-readable storage medium, and these computer-readables store
Media have the configuration reference hemozoin nonlinear response information as data structure 424.In one embodiment, should
Modeled reference comparison information is comprised with reference to hemozoin nonlinear response information.In one embodiment, joined
The circuit 134 being set to comparison non-linear multiple-harmonic response energy distribution curve comprises one or more computer-readable storage matchmaker
Body, these computer-readable storage mediums have the configuration reference hemozoin nonlinear response letter as data structure 424
Breath.In one embodiment, this reference hemozoin nonlinear response information is included in the non-linear sound that in situ detection arrives
Answer at least one in information, hemozoin spectral information or hemozoin non-linear susceptibility information.
In one embodiment, system 100 especially comprises circuit 136, this circuit 136 be configured to by (a) with use warp
The pulse electromagnetic energy of spatial patterned stimulates the non-linear multiple-harmonic response energy that at least one volume of focus inquired after is associated
Amount distribution curve compares with reference to hemozoin nonlinear response information with (b).
In one embodiment, system 100 especially comprises circuit 138, and this circuit 138 is configured to draw by magnetic means
Send out the hemozoin nanoparticle in a biological specimen vibration, translate or rotate at least one, this biological specimen
In hemozoin nanoparticle this initiation vibration, translate and rotate in the feature of at least one and the persistent period
Be enough to affect the integrity of the organelle of malaria original endoparasite.In one embodiment, it is configured to cause by magnetic means
The vibration of the hemozoin nanoparticle in one biological tissue, translate or rotate in the circuit 138 of at least one comprise
One flexible circuit, this flexible circuit has and is configured to apply to produce the one or more of magnetic field in the case of current potential existing
Conductive trace.In one embodiment, it is configured to cause the hemozoin in a biological tissue to receive by magnetic means
The vibration of rice corpuscles, translate or rotate in the circuit 138 of at least one comprise a printed circuit, this printed circuit have by
It is configured to depositing one or more conductive trace producing magnetic field under the application of a current.In one embodiment, quilt
Be configured for magnetic means cause hemozoin nanoparticle in a biological tissue vibration, translate or rotate in extremely
The circuit 138 of few one comprises at least one in receptor 1206, emitter 1210 or transceiver 1208.An embodiment party
In case, it is configured to the vibration with the hemozoin nanoparticle in one biological tissue of magnetic means initiation, translates or revolve
The circuit 138 of at least one in Zhuaning comprises at least one electromagnet.In one embodiment, it is configured to use magnetic means
Cause the hemozoin nanoparticle in a biological tissue vibration, translate or rotate in the circuit 138 of at least one
Comprise at least one permanent magnet.
In one embodiment, system 100 especially comprises circuit 140, and this circuit is configured to transmit and compare non-thread
Property the multiple-harmonic response comparison information that is associated of energy distribution curve.
In one embodiment, system 100 especially comprises circuit 142, and this circuit is configured to transmit and with magnetic side
Formula cause hemozoin nanoparticle vibration, translate and rotate in the process information that is associated of at least one.
In one embodiment, system 100 especially comprises circuit 144, and this circuit is configured to configure in dark field detection
Or Lay is because detecting the scattering energy from a biological tissue at least one in Burger detection configuration.An embodiment
In, the circuit 144 being configured to detection scattering energy comprises at least one sensor 442, and this sensor is configured in details in a play not acted out on stage, but told through dialogues
Detection configuration receives a part for scattering energy.In one embodiment, the circuit 144 of detection scattering energy it is configured to
Comprising at least one sensor 442, this sensor is configured to receive in Lay is because of Burger detection configuration one of scattering energy
Point.In one embodiment, the circuit 144 being configured to detection scattering energy comprises a lens arra molectron, and this is saturating
Lens array molectron be configured to receive from this biology tested scatter energy at least some of.An embodiment
In, it is configured to the circuit 144 of detection scattering energy and comprises a Lay and be configured because of Burger dyeing illuminating assembly, this molectron
For receive from this biology tested scatter energy at least some of.In one embodiment, detection scattering it is configured to
The circuit 144 of energy comprises at least one Lay because of Burger light filter.
In one embodiment, system 100 especially comprises circuit 146, and this circuit 146 is configured to respond to detect
Scattering energy information and with reference to hemozoin nanoparticle scattering energy information between comparison and magnetically disturb
Hemozoin nanoparticle in one biological tissue.In one embodiment, it is configured to disturb one by magnetic means
The circuit 146 of the hemozoin nanoparticle in individual biological tissue comprises a coil assembly, and this coil assembly is joined
Be set to magnetic means cause hemozoin nanoparticle in a biological tissue vibration, translate or rotate at least
One.In one embodiment, it is configured to the hemozoin nanoparticle in one biological tissue of magnetic means interference
The circuit 146 of son comprises one or more conductive trace, and these conductive traces are configured to cause the malaria in a biological tissue
The vibration of protozoon pigment nanoparticle, translate or rotate at least one.In one embodiment, it is configured to use magnetic
Mode disturbs the circuit 146 of the hemozoin nanoparticle in a biological tissue to comprise one or more processor 404, this
A little processors produce a control signal when being activated, and this control signal causes the scattering energy and reference plasmodium detected
Comparison between pigment nanoparticle scattering energy information.
In one embodiment, system 100 especially comprises circuit 148, and this circuit 148 is configured to join in dark field detection
Put to stimulate the electromagnetic energy of an effective dose and be irradiated in one or more districts of a biological tissue with from this biology group
Knit generation scattering energy.In one embodiment, the circuit 148 being configured to irradiate the electromagnetic energy stimulation of this effective dose wraps
Containing a lens arra molectron, this lens arra molectron is configured to stimulate one or more incident electromagnetic energy focus on
Above and energy is scattered from tested reception of this biology to this biology is tested.
In one embodiment, system 100 especially comprises circuit 150, and this circuit is configured to detection and by electromagnetic energy
Amount stimulates the non-thread that the hemozoin nanoparticle at least one volume of focus of the biological tissue inquired after is associated
Property multiple-harmonic response energy.In one embodiment, the circuit 150 being configured to detect non-linear multiple-harmonic response energy wraps
Containing at least one charge coupled device, this charge coupled device is configured to detection and stimulates, with by electromagnetic energy, at least inquired after
Second harmonic response, third harmonic response or the 4th harmonic wave that hemozoin nanoparticle in individual volume of focus is associated ring
At least one in Ying.In one embodiment, the circuit 150 being configured to detect non-linear multiple-harmonic response energy comprises
At least one UV-visible diode array detector, this detector is inquired after with being stimulated by electromagnetic energy for detection
The second harmonic that hemozoin nanoparticle at least one volume of focus is associated responds, third harmonic response or the 4th
At least one in harmonic response.In one embodiment, it is configured to detect the circuit of non-linear multiple-harmonic response energy
150 comprise the circuit being configured to detect the multiple-harmonic photo response radiated in a percutaneous manner.
In one embodiment, be configured to detect the circuit 150 of non-linear multiple-harmonic response energy comprise one or
Multiple sensors 442, these sensors are received for the one or more hemozoins detected in this at least one volume of focus
The nonlinear response distribution curve of rice corpuscles.In one embodiment, it is configured to detect non-linear multiple-harmonic response energy
Circuit 150 comprise one or more sensor 442, this sensor for detect in this at least one volume of focus or
The spectral response of multiple hemozoin nanoparticles.In one embodiment, it is configured to detect non-linear multiple-harmonic ring
Should be able to circuit 150 comprise be configured to detect in position with by the electromagnetic energy of the pulse multiplex multiplexing through spatial patterned
Stimulate the non-linear multiple-harmonic response energy that the hemozoin nanoparticle at least one volume of focus inquired after is associated
Circuit.In one embodiment, the circuit 150 being configured to detect non-linear multiple-harmonic response energy comprises an optics
Molectron 112 and at least one sensor 442, for collecting and detect via collected outside pattern by through space pattern
The electromagnetic energy of the pulse multiplex multiplexing changed stimulates in second harmonic response, third harmonic response or the 4th harmonic response drawn
At least one.In one embodiment, the circuit 150 being configured to detect non-linear multiple-harmonic response energy comprises one
Optical package 112 and at least one sensor 442, for collecting via Lay because of Burger detection configuration and detect by warp
The electromagnetic energy of the pulse multiplex multiplexing of spatial patterned stimulates the second harmonic response, third harmonic response or the 4th that draw humorous
At least one in wave response.
In one embodiment, system 100 especially comprises circuit 152, and this circuit is configured to produce an effective dose
Pulse electromagnetic energy stimulate to draw from this biological tissue at least one volume of focus of a biological tissue
The nonlinear response of hemozoin nanoparticle.In one embodiment, the feature of the nonlinear response drawn and
Persistent period be enough to regulate the biological activity of the malaria infection factor.
The absorption of electromagnetic radiation, transmit, scattering etc. is in various biological tissues, biological specimen, equipment, other material or class
Like different between thing.For example, the scope of about 800 nanometers to about 1300 nanometers is photonic absorption for skin tissue
A scope (produce for effective optical power skin on transmit for an optimal district) minimum with scattering.Therefore,
In one embodiment, power radiation assembly 104 the peak emission wavelength of the electromagnetic stimulation produced is selected as making institute
Pay close attention to the delivery of sample and maximize from the detection of paid close attention to sample.For example, in order to improve the warp of an electromagnetic stimulation
Skin transmission and the subsequent detection to produced nonlinear optical response, select the peak emission wavelength of electromagnetic stimulation about
In the range of 1000 nanometers to about 1300 nanometers.This receives causing the nonlinear optical response from hemozoin about 500
Rice (produces for second harmonic to about 650 nanometers；The half of wavelength), about 333 nanometers to about 433 nanometers (for third harmonic
Produce；/ 3rd of wavelength) etc. in the range of.In one embodiment, power radiation assembly 104 electromagnetism produced
The one or more peak emission wavelength stimulated are selected as the nonlinear optical response causing hemozoin in infringement heredity
Launch in the wave-length coverage of material.For the effective light on such as armarium, medical facilities, in vivo goods or the like
For learning power transmission, other scope is probably more preferably.
In one embodiment, the circuit 152 being configured to produce the pulse electromagnetic energy stimulation of this effective dose comprises
At least one first power radiation device and at least one the second power radiation device are used for multiplexing nonlinear response chemical examination, should
First power radiation utensil has about 690 nanometers peak emission wavelength to about 2100 nanometers, and this second power radiation utensil has about
1000 nanometers are to the peak emission wavelength of about 2000 nanometers.In one embodiment, it is configured to produce the arteries and veins of this effective dose
The circuit 152 that rushing electromagnetic energy stimulates comprises power radiation assembly 104, and this power radiation assembly is configured to through space pattern
The electromagnetic energy of the pulse multiplex multiplexing changed stimulates inquires after at least one volume of focus.
In one embodiment, the circuit 152 being configured to produce the pulse electromagnetic energy stimulation of this effective dose comprises
One or more laser instrument, laser diode and light emitting diode.In one embodiment, it is configured to produce this effective
The circuit 152 that the pulse electromagnetic energy of amount stimulates comprises one or more quantum dot, Organic Light Emitting Diode, tiny cavity light-emitting two pole
Pipe and polymer LED.In one embodiment, it is configured to produce the pulse electromagnetic energy thorn of this effective dose
The circuit 152 swashed comprises one or more femtosecond laser.In one embodiment, it is configured to produce this effective dose
The circuit 152 that stimulates of the pulse electromagnetic energy radioactive source of energy that comprises a patterning.In one embodiment, joined
The circuit 152 that being set to produce the pulse electromagnetic energy of this effective dose stimulates comprises and is configured to deliver a spaced apart energy thorn
The lens arra swashed, this lens arra at least has firstth district and secondth district, and this secondth district has difference
Depth of focus in this firstth district.
In one embodiment, system 100 especially comprises circuit 154, and this circuit 154 is configured to produce through multichannel again
Pulse electromagnetic energy stimulate, this electromagnetic energy stimulate have from about 400 m. gigawatt (GW)s to the peak power of about 8 TW terawatts.
In one embodiment, system 100 especially comprises circuit 156, and this circuit 156 is configured to multiplexed
Pulse electromagnetic energy stimulate be directed to a biology tested in multiple volume of focus on.
In one embodiment, system 100 especially comprises circuit 158, and this circuit is configured to detection and by through multichannel
The pulse electromagnetic energy of multiplexing stimulates in one or more the interior biological tissue in the multiple volume of focus inquired after many
The multiple-harmonic response that individual hemozoin nanoparticle is associated.In one embodiment, it is configured to detect multiple-harmonic ring
The circuit 158 answered comprises at least one outside direction sensor, for detection in position and by multiplexed pulse electromagnetic
Energy stimulates multiple-harmonic that the multiple hemozoin nanoparticles in the biological tissue inquired after are associated, that radiated to ring
Should.
In one embodiment, system 100 especially comprises a magnetic field component 160, and this magnetic field component 160 is configured to
Producing a magnetic field, the feature in this magnetic field and persistent period be enough in vivo be directed at multiple hemozoin by magnetic means
Nanoparticle.In one embodiment, magnetic field component 160 comprises a radio-frequency transmissions being configured to produce radiofrequency signal
Device.In one embodiment, magnetic field component 160 comprises and is configured to produce the one or more of one or more radio-frequency pulse
Coil.In one embodiment, to be configurable for removably being attached to a biology tested for medical diagnosis device
Biological surface.
In one embodiment, system 100 especially comprises a physical connection element, and this physical connection element is configured
For details in a play not acted out on stage, but told through dialogues electromagnetic energy being radiated at least one in assembly, magnetic field component and optical energy sensor cluster with detachable side
Formula is attached to a tested biological surface of biology.
In one embodiment, system 100 especially comprises a magnetic field producer that can actively control 162, this magnetic field
Generator is configured to deliver the magnetic stimulation of a change, and the dosage in this magnetic field be enough to cause the malaria in a biological specimen
Protozoon pigment nanoparticle produces heat.In one embodiment, the magnetic field producer 162 that can actively control comprises and is configured to
Producing and deliver the circuit that electromagnetic energy stimulates, feature and persistent period that this electromagnetic energy stimulates are sufficient so that by electromagnetism
Energy stimulates the hemozoin nanoparticle in the biological specimen inquired after to produce heat energy.In one embodiment, can be actively
The magnetic field producer 162 controlled comprises an electric coil molectron, and this electric coil molectron produces a magnetic field when being energized,
The feature in this magnetic field and persistent period are for causing Blang in the biological specimen comprising hemozoin nanoparticle
(Brownian) one or more during process and Neil (Neelian).In one embodiment, can actively control
Magnetic field producer 162 comprise one for the field-generating coil molectron in magnetic field applying change.An embodiment
In, the magnetic field producer 162 that can actively control comprises a volume coils arrangement, and this volume coils arrangement comprises for producing one
Multiple coils in individual Circular Polarisation magnetic field.In one embodiment, the magnetic field producer 162 that can actively control comprise one or
Multiple electromagnets.
In one embodiment, the magnetic field producer 162 that can actively control comprises one or more alternating current magnet.?
In one embodiment, the magnetic field producer 162 that can actively control comprises and is configured to produce the one or more of a magnetic field
Coil, the feature in this magnetic field and persistent period be enough to make the district comprising hemozoin nanoparticle in plasmodium
Temperature increase about 3 DEG C to about 22 DEG C.In one embodiment, the magnetic field producer 162 that can actively control comprises and is configured to
Producing one or more coils in a magnetic field, the feature in this magnetic field and persistent period be enough to make the interior malaria existed of biological specimen
The temperature increase about 3 DEG C to about 10 DEG C in the district containing hemozoin of in original endoparasite.In one embodiment, may be used
The magnetic field producer 162 actively controlled comprises the one or more coils being configured to produce a magnetic field, the feature in this magnetic field
And the temperature increase about 3 DEG C in the district comprising hemozoin nanoparticle that the persistent period be enough to make in malaria original endoparasite
To about 4 DEG C.
In one embodiment, the magnetic field producer 162 that can actively control produces a magnetic field, the feature in this magnetic field with
And the persistent period be enough to make the temperature in the district comprising hemozoin nanoparticle of malaria original endoparasite increase.At one
In embodiment, the magnetic field producer 162 that can actively control produces a magnetic field, and the intensity in this magnetic field or persistent period be enough to make
The decay of activity of the malaria infection factor.In one embodiment, the magnetic field producer 162 that can actively control provides a magnetic
, the intensity in this magnetic field or persistent period be enough to regulate the heme polymerase activity of the malaria infection factor.
In one embodiment, the magnetic field producer 162 that can actively control provides a magnetic field, the feature in this magnetic field with
And the persistent period be enough to improve plasmodium impact, and substantially without destroy wrapped up malaria original endoparasite erythrocytic completely
Property.In one embodiment, the magnetic field producer 162 that can actively control provides a magnetic field, the feature in this magnetic field and holding
The continuous time be enough to make the temperature in a district of the malaria original endoparasite in biological specimen increase, and this temperature increase be enough to cause this malaria
In original endoparasite because of the programmed cell death of thermal initiation.
In one embodiment, the magnetic field producer 162 that can actively control provides a magnetic field, the feature in this magnetic field with
And the persistent period be enough to cause the programmed cell death of the host cell being loaded with the malaria infection factor.An embodiment
In, the magnetic field producer 162 that can actively control provides a magnetic field, and the feature in this magnetic field and persistent period be enough to make biological sample
Temperature in one district of the malaria original endoparasite in Ben increases, and this temperature increase be enough to reduce parasitemia level.At one
In embodiment, the magnetic field producer 162 that can actively control produces an AC magnetic field, the feature of this AC magnetic field and continuing
Time be enough to cause the temperature in the district comprising hemozoin nanoparticle in malaria original endoparasite to increase, and improves
Malaria original endoparasite affects, and has wrapped up plasmodial erythrocytic integrity substantially without destruction.
In one embodiment, the magnetic field producer 162 that can actively control comprises one or more conductive coil, these
Conductive coil is configured to respond to applied electric current and produces a time-varying magnetic field, the feature of this time-varying magnetic field and continuing
The hemozoin nanoparticle that time be enough to cause in biological specimen due to the one during Brown motion and Neil or
Many persons and produce heat.In one embodiment, the magnetic field producer 162 that can actively control produces a magnetic field, this magnetic field
Feature and persistent period are adequate to bring about the pyrolytic damage to the organelle film in the malaria original endoparasite in biological specimen.At one
In embodiment, the magnetic field producer 162 that can actively control comprises at least one radiofrequency launcher, and these radiofrequency launchers comprise
It is configured to produce one or more radio-frequency coils that the radio frequency of localization stimulates.
In one embodiment, the magnetic field producer 162 that can actively control the most at least produces one
First electromagnetic energy stimulates and second electromagnetic energy stimulates, the feature of this first electromagnetic energy stimulation and persistent period
Be enough to by the hemozoin nanoparticle in one biological tissue of magnetic means alignment, the feature that this second electromagnetic energy stimulates
And the persistent period be enough to cause the vibration of hemozoin nanoparticle in this biological tissue by magnetic means, translate or revolve
At least one in Zhuaning.In one embodiment, the caused hemozoin nanoparticle in a biological tissue
Vibration, translate and rotate at least one be enough to affect the integrity of the organelle of the malaria infection factor.A reality
Execute in scheme, the vibration of the caused hemozoin nanoparticle in a biological tissue, translate and rotate in extremely
Few one be enough to affect the integrity of plasmodial digestibility food vacuole.In one embodiment, a caused biology
The vibration of the hemozoin nanoparticle in tissue, translate and rotate at least one be enough to the Asia destroyed in vivo
Ferrum haemachrome polymerization process.
In one embodiment, system 100 especially comprises one and calculates device 402, and this calculating device is with operable side
Formula is connected to this magnetic field producer that can actively control.In one embodiment, calculate device 402 and comprise one or more place
Reason device 404, for controlling at least one in magnetic field on-time, magnetic field intensity, field frequency or field waveform.
In one embodiment, system 100 especially comprises details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly, and this details in a play not acted out on stage, but told through dialogues electromagnetic energy is put
Penetrate assembly to be configured to stimulate at least one volume of focus inquiring after biological tissue with multimode details in a play not acted out on stage, but told through dialogues.
In one embodiment, system 100 especially comprises one or more power supply 700.In one embodiment, electricity
Source 700 can use electromagnetic mode, magnetic means, ultrasonic power, optical mode, inductively, electrically or capacitive way couple
To one or more power radiation assemblies 104.In one embodiment, power supply 700 is held by monitor or processing means 102
Carry.In one embodiment, power supply 700 includes at least one rechargeable power supply 702.In one embodiment, electricity
Source 700 is configured to wirelessly receive power from a remote power supply.
In one embodiment, monitor or processing means 102 comprise one or more by biological tested (such as, people)
The electric organ 704 of energy supply.In one embodiment, the electric organ 704 of this biological tested energy supply is configured to from such as one
Or the motion pick energy in multiple joint.In one embodiment, the electric organ 704 of biological tested energy supply is configured with
Thermoelectric generator 706, piezoelectric generating unit 708, dynamo-electric electric organ 710 (such as, MEMS (MEMS) electric organ or similar
Thing), at least one in biomechanics energy acquisition electric organ 712 or the like gathers by the energy of biological tested generation.
In one embodiment, the electric organ 704 of biological tested energy supply is configured to gather by biological tested generation
Heat energy.In one embodiment, thermoelectric generator 706 is configured to gather by the heat of biological tested dissipation.An enforcement
In scheme, the electric organ 704 of biological tested energy supply is configured to gather by biological tested any physical motion or movement (example
As, walking) energy that produces.For example, in one embodiment, the electric organ 704 of biological tested energy supply is configured to
Collection is by the energy of the mobile generation in the tested interior joint of biology.In one embodiment, biological tested energy supply send out
Electrical equipment 704 is configured to gather the energy of the mobile generation by the tested interior fluid (such as, biofluid) of biology.
In the middle of power supply 700, example is including (but not limited to) one or more button cells, chemical storage batteries, fuel electricity
Pond, secondary cell, lithium ion battery, micro-electricity paster, nickel metal hydride battery, silver-zinc battery, capacitor, ultracapacitor,
Thin-film secondary battery, ultra-capacitor (ultra-capacitors), zinc-air battery or the like.Power supply 700 other non-
Limitative examples comprises one or more electric organ, and (such as, electric electric organ, heat energy are to electric energy electric organ, mechanical energy to electric energy
Electric organ, micron electric organ, nanometer generating device or the like), such as thermoelectric generator, piezoelectric generating unit, dynamo-electric electric organ, life
Material resources energy acquisition electric organ or the like.In one embodiment, monitor or processing means 102 comprise one or many
Individual electric organ, these electric organs are configured to collection machinery energy from such as ultrasound wave, mechanical vibration, blood flow or the like.?
In one embodiment, monitor or processing means 102 comprise one or more power receiver 732, these power receivers
732 are configured to ex vivo or sv power supply reception power.In one embodiment, power supply in vivo comprises
Thermoelectric generator, piezoelectric generating unit, electromechanics can be at least one in power generator or biomechanics energy acquisition electric organ.
In one embodiment, power supply 700 comprises thermoelectric generator, piezoelectric generating unit, dynamo-electric electric organ or Biological Strength
Learn at least one in energy acquisition electric organ, and button cell, chemical storage batteries, fuel cell, secondary cell, lithium ion
Battery, micro-electricity paster, nickel metal hydride battery, silver-zinc battery, capacitor, ultracapacitor, thin-film secondary battery, super electric
At least one in container or zinc-air battery.In one embodiment, to comprise at least one rechargeable for power supply 700
Power supply.
In one embodiment, monitor or processing means 102 comprise a power supply 700, and this power supply 700 comprises thermoelectricity
At least one in electric organ, piezoelectric generating unit, dynamo-electric electric organ or biomechanics energy acquisition electric organ.An embodiment party
In case, power supply 700 is configured to management and radiates the electromagnetic energy of an effective dose from one or more power radiation assemblies 104
Stimulate the dutycycle being associated.In one embodiment, power supply 700 is configured to management and from one or more power radiation
Assembly 104 radiates the sterilization energy of an effective dose stimulates the dutycycle being associated.
In one embodiment, power supply 700 is configured to management and causes in a biological tissue by magnetic means
The vibration of hemozoin nanoparticle, translate or rotate in the dutycycle that is associated of at least one.An embodiment
In, power supply 700 is configured to management and compares the dutycycle being associated, this compare be by with the arteries and veins through spatial patterned
Rush non-linear multiple-harmonic response energy distribution curve and ginseng that electromagnetic energy stimulates at least one volume of focus inquired after to be associated
Examine hemozoin nonlinear response information to compare.In one embodiment, system 100 especially comprises an energy storage
Cryopreservation device.In one embodiment, during this energy accumulating device comprises battery, capacitor or machinery energy storage device at least
One.
Fig. 2 A show the system 100 for regulating plasmodium parasitism activity.For regulate plasmodium parasitism activity it is
System 100 especially comprises circuit 128, and this circuit is configured to produce a magnetic stimulation, the feature of this magnetic stimulation and continuing
Time be enough to cause the hemozoin nanoparticle in a biological specimen in position in, in vivo, in vitro or class
As deliver the hyperthermia therapy magnetically caused.It is included in vivo or in vitro in position.An enforcement
In scheme, comprise, for regulating the system 100 of plasmodium parasitism activity, the circuit being configured to dynamically control magnetic stimulation
208.In one embodiment, the circuit 208 being configured to dynamically control magnetic stimulation comprises one or more processor
404, these processors are connected to the circuit 202 being configured to produce electromagnetic stimulation to operably, and are configured to
Manage the one or more parameters being associated with the delivery to the tested district of biology of the pulsed magnetic sexual stimulus.One
In individual embodiment, the circuit 208 being configured to dynamically control magnetic stimulation comprises one or more processor 404, these
Processor be configured to regulation with generation electromagnetic stimulation be associated delivery system parameter, spaced apart delivery pattern parameter or
At least one in temporal delivery pattern parameter.
Fig. 2 B show the system 100 for monitoring/regulate plasmodium parasitism activity optically.An embodiment party
In case, system 100 comprises scanning/optical projection system 210 and the detection being at least one lower operation of the control calculating device 402
Subsystem 212.System 100 can be implemented by various ways, the most such as 6,445, No. 362 United States Patent (USP)s,
Optically-based scanning device described in one or more in U.S.2006/0284790 and/or U.S.2005/0020926 be
System.
In one approach, scanning/optical projection system 210 towards the tested eyes 220 of biology by one or more electricity
Magnetic energy stimulates 214 guiding by beam splitter 216 and by optical lens molectron 218.For example, system 100 is by one
The electromagnetic energy of individual effective dose stimulates 214 to be directed in the tested one or more volume of focus of biology produce from this life
The radiation of the tested scattering of thing, and use dark field detection configuration to detect radiation 225 at least some of of this scattering.
In one illustrative embodiment, system 100 uses one or more power radiation assembly 104, such as laser
Diode or fiberoptic connection laser instrument, have from about 690 nanometers to the peak emission wavelength of about 2100 nanometers, for illumination radiation
At least one in 214.Illumination radiation 214 is scanned across such as one grating pattern or Li Shayu by monitoring/regulation system 210
(Lissajous) pattern.
Scanned illumination radiation 214 is coupled in eyes, at this by optical lens molectron 218 by the pupil of eyes
At pupil, illuminating bundle 214 is irradiated to retina 222.In certain methods, optical lens molectron 218 can provide one
Beam 224, this beam 224 converges in paid close attention to field, such as the surface of retina 222 or near.In other method
In, beam can be made generally to collimate.Beam splitter 216 can be any one in multiple optical texture, and these optical textures can
To transmit and/or redirecting light at least some of along one or more Path selection.An illustrative embodiment party
In case, beam splitter optionally can transmit in response to one or more optical wavelength and/or redirecting light at least some of.
As will be described herein, difference illumination arrangement is used to collect some light the light returned from the field paid close attention to.Beam splitter 216 can
To be configured to the light being in an input wavelength is selectively transmitted to eyes, simultaneously selectively redirect and be in one
Dispersion wavelength and/or the light of this input wavelength.It should be noted that beam splitter can also reset in response to the polarization of light or other characteristic
To all or part of of the light returned.
Fig. 3 A show hemozoin monitoring device 300, wherein can implement one or more methods or technology.Malaria is former
Worm pigment monitoring device 300 especially comprises a sensor cluster 440, and this sensor cluster is configured to detection and by electromagnetic energy
(such as, pulse electromagnetic energy stimulates, through the electromagnetic energy stimulation of spatial patterned, multiplexed electromagnetic energy in amount stimulation
Stimulate, through spatial patterned pulse multiplex multiplexing electromagnetic energy stimulate, through the time patterning electromagnetic energy stimulate or class
Like thing) hemozoin nanoparticle in a biological tissue in multiple volume of focus of inquiring after be associated non-linear many
Harmonic response distribution curve.In one embodiment, sensor cluster 440 is configured with the illumination of one or more difference
Configuration (such as, dark-ground illumination, Lay are because of Burger illumination or similar illumination) detects non-linear multiple-harmonic response distribution curve.One
In individual embodiment, sensor cluster 440 is configured with during dark field detection configuration or Lay configure because of Burger detection at least
One detects non-linear multiple-harmonic response distribution curve.In one embodiment, sensor cluster 440 is configured to optionally
The spectral matching factor that ground uses dark field detection configuration or Lay to detect hemozoin because of at least one in Burger detection configuration is special
Property.
Hemozoin monitoring device 300 can especially comprise one or more computer-readable storage medium, these meters
Calculation machine readable memory medium comprises the executable instruction being stored thereon, and these executable instructions ought perform on a computer
Time instruction calculate device 402 and call and reference be associated one or many of hemozoin nonlinear response information from storage device
Individual parameter, and perform the ratio of the non-linear multiple-harmonic response distribution curve detected and the one or more parameters called
Relatively.In one embodiment, hemozoin monitoring device 300 comprises a transceiver 1208, and this transceiver 1208 is simultaneously
Ground or sequentially launch or reception information.
Fig. 3 B show medical diagnosis device 310, wherein can implement one or more methods or technology.Medical diagnosis fills
Putting 310 and especially comprise circuit 312, this circuit is configured to produce multiplexed pulse electromagnetic energy to stimulate, this electromagnetic energy
Amount stimulation has from about 400 m. gigawatt (GW)s to the peak power of about 8 TW terawatts.In one embodiment, medical diagnosis device 310
Comprise circuit 156, this circuit be configured to stimulate multiplexed pulse electromagnetic energy be directed to a biology tested in
Multiple volume of focus on.In one embodiment, medical diagnosis device 310 comprises circuit 158, and this circuit is configured to inspection
Survey and stimulated one or more the interior life in the multiple volume of focus inquired after by multiplexed pulse electromagnetic energy
The multiple-harmonic response that multiple hemozoin nanoparticles in fabric texture are associated.
Fig. 3 C show medical diagnosis device 320, wherein can implement one or more methods or technology.Medical diagnosis fills
Put 320 and especially comprise a details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly 104a.In one embodiment, details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation group
Part 104a is configured to that multimode details in a play not acted out on stage, but told through dialogues is inquired after stimulation and is delivered at least one blood vessel.Medical diagnosis device 320 can especially wrap
Containing a magnetic field component 322.In one embodiment, this magnetic field component 322 produces magnetic field, the feature in this magnetic field and continuing
Time be enough in vivo be directed at multiple hemozoin nanoparticle by magnetic means.Medical diagnosis device 320 especially comprises
One optical energy sensor cluster 440a.In one embodiment, this optical energy sensor cluster 440a is configured to
Detection carrys out free multimode details in a play not acted out on stage, but told through dialogues and inquires after multiple hemozoin nanoparticles that stimulation inquired after in the presence of a magnetic field
Scattering optical energy.
Fig. 3 D show hemozoin monitoring device 330 in situ, wherein can implement one or more methods or technology.
Hemozoin monitoring device 330 especially comprises excitation component 104b that can actively control in situ, and this can actively control
Excitation component is configured to stimulate a pulse electromagnetic energy through spatial patterned be delivered to one or more volume of focus,
And it is configured to draw non-from the hemozoin nanoparticle in a biological tissue in the plurality of volume of focus
Linear multiple-harmonic response message.In one embodiment, hemozoin monitoring device 330 comprises a control device in situ
332, this control device be connected to operably this excitation component 104b that can actively control and be configured to regulation with
Through spatial patterned pulse electromagnetic energy stimulate delivery be associated numerical aperture, spaced apart delivery pattern parameter or time
At least one delivered in pattern parameter between.In one embodiment, the excitation component 104b quilt that this can actively control
It is configured at least one in the parameter that regulation is associated with peak power, peak irradiance, focal spot size or pulse width.
Fig. 3 E show anti-malarial therapy device 340, wherein can implement one or more methods or technology.A reality
Executing in scheme, anti-malarial therapy device 340 especially comprises a sensor cluster 440, and this sensor cluster comprises at least one
Sensor 442, this sensor is configured to detection and at least one being stimulated the biological tissue inquired after by electromagnetic energy is gathered
The non-linear multiple-harmonic response energy that hemozoin nanoparticle in burnt volume is associated.In one embodiment, anti-
Malaria treatment device 340 comprises a power radiation assembly 104, and this power radiation assembly is configured to deliver an effective dose
Electromagnetic energy stimulates to draw the nonlinear optical response from the hemozoin nanoparticle in this biological tissue, is drawn
The feature of nonlinear response and the persistent period be enough to regulate the biological activity of the malaria infection factor in this biological tissue.?
In one embodiment, anti-malarial therapy device 340 comprises one and calculates device 402, and this calculating device joins to operably
Receiving at least one sensor 442 and the power radiation assembly 104 of sensor cluster 440, this calculating device 402 is configured to
One control signal is supplied to power radiation assembly.
Fig. 4 A show an equipment 460, wherein can implement one or more methods or technology.Equipment 460 especially wraps
Containing a magnetic field producer that can actively control 462 and be connected to this magnetic field producer that can actively control to operably
One calculating device of 462.In one embodiment, the magnetic field producer 462 that this can actively control is configured to deliver one
The magnetic stimulation of individual change, the dosage of this magnetic stimulation be enough to the hemozoin nanoparticle caused in a biological specimen
Produce heat.In one embodiment, calculate device 402 and be connected to this magnetic field producer that can actively control to operably
462, and comprise one or more processor 404, be used for controlling the magnetic field on-time, magnetic field intensity, field frequency or
At least one in field waveform.
Fig. 4 B show an equipment 470, wherein can implement one or more methods or technology.An embodiment
In, equipment 460 comprises a magnetic field producer 472, this magnetic field producer 472 simultaneously or sequentially produce at least one first
Electromagnetic energy stimulates and second electromagnetic energy stimulates, and feature and persistent period that this first electromagnetic energy stimulates be enough to
With magnetic means alignment one biological tissue in hemozoin nanoparticle, this second electromagnetic energy stimulate feature and
Persistent period be enough to cause the vibration of hemozoin nanoparticle in this biological tissue by magnetic means, translate or rotate
At least one.
Fig. 5 show the example of the method 500 for detecting the situation being associated with the erythrocyte by Infected With Plasmodium.?
At 510, method 500 comprises will stimulate at least one inquired after to gather with the pulse electromagnetic energy through spatial patterned via circuit
The non-linear multiple-harmonic response distribution curve that burnt volume is associated compares with reference to hemozoin nonlinear response information.
At 512, use circuit will to stimulate, with the pulse electromagnetic energy through spatial patterned, at least one the volume of focus phase inquired after
The non-linear multiple-harmonic response distribution curve of association comprises with comparing with reference to hemozoin nonlinear response information: produce
Non-linear multiple-harmonic response distribution curve and the reference hemozoin nonlinear response being configured as physical data structure 424
The comparison of information.At 514, use circuit will to stimulate, with the pulse electromagnetic energy through spatial patterned, at least one inquired after
The non-linear multiple-harmonic response distribution curve that volume of focus is associated compares with reference to hemozoin nonlinear response information
Relatively comprise: in the third harmonic response second harmonic drawn is responded, drawn and the 4th harmonic response drawn
One or more with compare with reference to hemozoin nonlinear response information.At 516, use circuit will with through sky
Between the pulse electromagnetic energy of patterning stimulate the non-linear multiple-harmonic response distribution that at least one volume of focus of inquiring after is associated
Curve compares comprise with reference to hemozoin nonlinear response information: the second harmonic response in situ detection arrived, former
Third harmonic response that position detects and in situ detection to the 4th harmonic response at least one with reference to plasmodium color
Element nonlinear response information compares.At 518, use circuit will to stimulate with the pulse electromagnetic energy through spatial patterned
The non-linear multiple-harmonic response distribution curve that at least one volume of focus inquired after is associated is non-linear with reference to hemozoin
Response message compares and comprises: the nonlinear photon detected response entered with reference to hemozoin nonlinear response information
Row compares.
At 520, method 500 can comprise further based on this non-linear multiple-harmonic detected response energy and reference
Hemozoin nonlinear response information relatively produce response.At 522, produce this respond packet containing providing and with through space
The pulse electromagnetic energy of patterning stimulates the non-linear multiple-harmonic response distribution song that at least one volume of focus inquired after is associated
The vision of line, audio frequency, sense of touch or sense of touch represent at least one.At 524, produce this respond packet containing detecting based on this
Non-linear multiple-harmonic response energy with determine with reference to the comparison of hemozoin nonlinear response information malaria situation existence,
Do not exist or one or more in seriousness.At 526, produce this respond packet containing the non-linear multiple-harmonic detected based on this
Response energy relatively determines malaria infection score with reference hemozoin nonlinear response information.
Fig. 6 show the example of method 600.At 610, method 600 comprises with the pulse electromagnetic energy through spatial patterned
Amount stimulates inquires after doubtful at least one volume of focus containing hemozoin.At 620, method 600 can be wrapped further
It is associated responding with the non-linear multiple-harmonic of doubtful at least one volume of focus containing hemozoin containing using circuit
Information compares with the information being associated with reference to hemozoin nonlinear response.At 630, method 600 can enter one
Step comprises the non-linear multiple-harmonic response phase using circuit to determine with doubtful at least one volume of focus containing hemozoin
The information of association is the most substantially similar with the information being associated with reference to hemozoin nonlinear response.At 640, method
600 can comprise further this at least one compared result is sent to user.
Fig. 7 show an example of method 700.At 710, method 700 comprises by stimulating with pulse electromagnetic energy
Inquire after the non-thread of hemozoin nanoparticle in the biological tissue that volume of focus is drawn in this volume of focus
Property multiple-harmonic response, this pulse electromagnetic energy stimulates and has from the resolution of about 300 nanometers to about 10 micron that [0.61* (put by peak value
Ejected wave length/numerical aperture)].At 712, draw non-linear multiple-harmonic respond packet containing by the electromagnetic energy of a pulse multiplex multiplexing
Amount stimulation is delivered to multiple volume of focus, and feature and persistent period that the electromagnetic energy of this pulse multiplex multiplexing stimulates be enough to draw
The out non-linear multiple-harmonic response of hemozoin nanoparticle present in this at least one volume of focus.At 720,
Method 700 can comprise use circuit further and by the response of non-linear multiple-harmonic and be configured as physical data structure 424
Compare with reference to hemozoin nonlinear response information.At 722, use circuit by the response of non-linear multiple-harmonic and reference
Hemozoin nonlinear response information compares and comprises: is responded by the second harmonic detected and is configured as physics number
Compare according to the reference hemozoin second harmonic response message of structure 424.At 724, use circuit by non-linear many
Harmonic response comprises with comparing with reference to hemozoin nonlinear response information: by the third harmonic response detected and quilt
Configure the reference hemozoin third harmonic response message as physical data structure 424 to compare.At 726, use
The response of non-linear multiple-harmonic is compared comprise with reference hemozoin nonlinear response information by circuit: the will detected
Four harmonic responses and reference hemozoin the 4th harmonic response information being configured as physical data structure 424 compare
Relatively.
At 730, method 700 can comprise further based on the response of non-linear multiple-harmonic and reference hemozoin non-thread
Property response message relatively produce response.
Fig. 8 show the example of method 800.At 810, method 800 comprises use circuit will be with doubtful containing plasmodium
The information that the non-linear multiple-harmonic response of at least one volume of focus of pigment is associated is with non-linear with reference to hemozoin
The information that multiple-harmonic response is associated compares, and this at least one volume of focus is with the pulse electromagnetic energy through spatial patterned
Amount stimulation is inquired after.
Fig. 9 show the example of in-situ method 900.At 910, method 900 comprises via one or more sensors 442
It is non-linear many that the multiple volume of focus detected and inquire after with the pulse electromagnetic energy stimulation through spatial patterned are associated
Harmonic response information.At 920, method 900 can comprise determine with through spatial patterned pulse electromagnetic energy stimulate come
Whether that the multiple volume of focus inquired after are associated, detected non-linear multiple-harmonic response message meets and one biological group
Not the existing of hemozoin nanoparticle in knitting, exist or threshold value index that seriousness is associated.At 930, method 900
Can comprise further and stimulate, with the pulse electromagnetic energy through spatial patterned, the multiple focusing bodies inquired after in response to determining
Whether long-pending that be associated, detected non-linear multiple-harmonic response message meets and the hemozoin in a biological tissue
The threshold value index that the existence of nanoparticle is associated is to produce response.
Figure 10 show the example of method 1000.At 1010, method 1000 comprises by the electromagnetic energy of pulse multiplex multiplexing
Amount stimulates and the tested interior multiple volume of focus of biology is carried out optionally energy supply, the electromagnetic energy of this pulse multiplex multiplexing
Feature and persistent period that amount stimulates be enough to extract one or more the interior parasite in free the plurality of volume of focus
With hemozoin nanoparticle multiple-harmonic response.At 1012, multiple volume of focus are optionally supplied
Can comprise one pulse electromagnetic energy of delivery to stimulate, feature and persistent period that this pulse electromagnetic energy stimulates be enough to extract
Freely parasite institute with the second harmonic response of hemozoin nanoparticle, third harmonic responds or the 4th harmonic wave
One or more in response.At 1020, method 1000 comprises multiple-harmonic response and the plasmodium color that generation one is drawn
Comparison between element multiple-harmonic characteristic information.
Figure 11 show the example of method 1100.At 1110, method 1100 comprises simultaneously one multimode details in a play not acted out on stage, but told through dialogues of generation
Inquire after stimulation and a magnetic stimulation.At 1120, method 1100 comprises detection in the presence of a magnetic field and by through many
The scattering response that multiple hemozoin nanoparticles that stimulation inquired after are associated is inquired after in the details in a play not acted out on stage, but told through dialogues of road multiplexing.At 1130,
Method 1100 can comprise the direction changing magnetic stimulation further.At 1140, method 1100 can be further contained in depositing
In the case of the magnetic field of change detection with inquired after, by multiplexed details in a play not acted out on stage, but told through dialogues, multiple hemozoins that stimulation inquired after and receive
The scattering response that rice corpuscles is associated.At 1150, method 1100 can comprise the intensity changing magnetic stimulation further.
At 1160, method 1100 can detect and by through multichannel further contained in the case of there is the magnetic field changed
The scattering response that multiple hemozoin nanoparticles that stimulation inquired after are associated is inquired after in the details in a play not acted out on stage, but told through dialogues of multiplexing.At 1162, inspection
Survey scattering respond packet contains the polarization to the scattered information manifested and detects.At 1164, detection scattering respond packet is contained in existence
In the case of magnetic field, detection inquires after, with by multiplexed details in a play not acted out on stage, but told through dialogues, multiple hemozoin nanoparticle phases that stimulation is inquired after
At least one in the diffraction light of association, reflection light or refraction light.
Figure 12 show the example of method 1200.At 1210, method 1200 comprises simultaneously one multimode details in a play not acted out on stage, but told through dialogues of generation
Inquiring after stimulation and a magnetic stimulation, the feature of stimulation is inquired after in this multimode details in a play not acted out on stage, but told through dialogues and the persistent period be enough to draw from one
The details in a play not acted out on stage, but told through dialogues scattering of the hemozoin nanoparticle in biological tissue responds, and feature and the persistent period of this magnetic stimulation be enough to
With the hemozoin nanoparticle in one biological tissue of magnetic means alignment.
At 1220, method 1200 is included in detection in the case of there is magnetic stimulation and visits with by multiplexed details in a play not acted out on stage, but told through dialogues
Ask the electromagnetic radiation being scattered that the multiple target areas in stimulating the biology inquired after tested are associated.
Figure 13 show the example of the method 1300 that plasmodium carries out thermal shock.At 1310, method 1300 comprises one
Individual time-varying magnetic field energy is delivered to biological tested, and this time-varying magnetic field energy is sufficient so that the hemozoin nanometer in this plasmodium
Particle produces heat energy.
Figure 14 show the doubtful tested method 1400 processed of a biology infected by malaria original endoparasite
Example.At 1410, method 1400 comprises by changing applied magnetic field fully so that plasmodium in plasmodium
Pigment nanoparticle produces heat energy and has a plasmodial biology tested interior delivery magnetic heater targetedly doubtful.?
At 1412, deliver magnetic heater targetedly and comprise outside for alternation magnetic via one or more magnetic power radiation assemblies
Field stimulates the doubtful one or more districts with malaria infection providing a biology tested, and this alternation external magnetic field stimulates
Feature and persistent period be enough to cause malaria original endoparasite because of the programmed cell death of thermal initiation.At 1414, delivering should
Magnetic heater comprises and a time-varying external magnetic field is delivered to tested doubtful of this biology has hemozoin targetedly
One or more districts.At 1416, deliver this targetedly magnetic heater comprise by a time-varying, spatially focus on outside
Magnetic field, portion is delivered to doubtful one or more districts with hemozoin that this biology is tested.At 1418, delivering should be for
Property magnetic heater comprise deliver an effective dose pulsed magnetic field stimulate to cause the plasmodium color in a biological tissue
One or more in element Blang's relaxation of nanoparticle and Neil relaxation, in this effective dose be enough to make malaria original endoparasite
Temperature increase in one district about 3 DEG C to about 22 DEG C.At 1420, deliver this targetedly magnetic heater comprise delivery one have
The pulsed magnetic field of effect dosage stimulates to cause Blang's relaxation and the Buddhist nun of the hemozoin nanoparticle in a biological tissue
One or more in your relaxation, this effective dose be enough to make the temperature increase about 3 DEG C in a district in malaria original endoparasite to arrive
About 10 DEG C.At 1422, deliver this targetedly magnetic heater comprise deliver an effective dose pulsed magnetic sexual stimulus to draw
Send out in Blang's relaxation of hemozoin nanoparticle in a biological tissue and Neil relaxation one or more, this has
Effect dosage be enough to make the temperature increase about 3 DEG C to about 4 DEG C in a district in malaria original endoparasite.At 1424, delivering should be for
Property magnetic heater comprise to be stimulated by one magnetic energy focused on via a radiofrequency launcher and be delivered to that doubtful to have malaria former
The biology of worm pigment is tested.At 1426, deliver this targetedly magnetic heater comprise change and the external magnetic field phase applied
At least one in dutycycle, magnetic field intensity, field frequency or the field waveform of association.
The method that Figure 15 show the Brown motion to a hemozoin nanoparticle or Neil process strengthens
The example of 1500.At 1510, method 1500 comprises use circuit and (a) is stung with the pulse electromagnetic energy through spatial patterned
Swash non-linear multiple-harmonic response distribution curve information same (b) the reference plasmodium color that at least one volume of focus inquired after is associated
Element nonlinear response information compares.At 1520, method 1500 comprise by one change magnetic field be applied to this at least one
Individual volume of focus, the magnetic field energy of this change is sufficient so that hemozoin nanoparticle to be there is vibration, translates or rotate
At least one.
Figure 16 show the example of the method 1600 processed that parasitizes plasmodium.At 1610, method 1600
Comprise and use circuit to stimulate at least one volume of focus inquired after relevant by (a) to the pulse electromagnetic energy through spatial patterned
The non-linear multiple-harmonic response distribution curve information of connection compares with reference to hemozoin nonlinear response information with (b).?
At 1620, method 1600 comprises and causes shaking of hemozoin nanoparticle in this at least one volume of focus by magnetic means
At least one in swinging, translate or rotating.At 1622, magnetically cause the plasmodium in this at least one volume of focus
The vibration of pigment nanoparticle, translate and rotate at least one comprise: one or more conductive coils are carried out energy supply,
Persistently be enough to produce the time of a time-varying magnetic field, feature and the persistent period of this time-varying magnetic field are sufficient so that hemozoin
Nanoparticle occur vibration, translate and rotate at least one.At 1624, at least one gathers magnetically to cause this
The vibration of the hemozoin nanoparticle in burnt volume, translate and rotate at least one comprise: be based in part on
The non-linear multiple-harmonic response distribution curve that this at least one volume of focus is associated is with reference to hemozoin nonlinear response
The comparison of information delivers the pulsed magnetic field of an effective dose to stimulate, to affect the organelle of a malaria infection factor
Integrity.At 1626, magnetically cause the vibration of hemozoin nanoparticle in a biological tissue, translation with
And at least one in rotating comprises: a radio-frequency coil molectron to be provided the applying electric current of an effective dose, this effective dose
Apply the feature of electric current and the persistent period be enough to produce a magnetic field, feature and the persistent period in this magnetic field are sufficient so that
There is vibration in hemozoin nanoparticle in one biological tissue, translate and rotate in one or more.1628
Place, magnetically cause the hemozoin nanoparticle in a biological tissue vibration, translate and rotate in extremely
Few one comprises: the pulsed magnetic field delivering an effective dose stimulates so that hemozoin nanometer in a biological tissue
Particle occur vibration, translate and rotate in one or more.At 1630, magnetically cause in a biological tissue
Hemozoin nanoparticle vibration, translate and rotate at least one comprise: deliver an effective dose electricity
Magnetic energy stimulates, so that during the hemozoin nanoparticle in a biological tissue vibration occurs, translates and rotate
One or more.
Figure 17 show the example of method 1700.At 1710, method 1700 comprises generation (a) and there is magnetic stimulation
In the case of with inquired after the scattering detected that the multiple target areas in the biological tissue that stimulation is inquired after are associated by details in a play not acted out on stage, but told through dialogues
Distribution curve information is with the comparison between (b) reference hemozoin details in a play not acted out on stage, but told through dialogues scattered information.At 1712, produce this and compare and comprise
Use circuit and will to be inquired after, by multiplexed details in a play not acted out on stage, but told through dialogues, the biology that stimulation is inquired after in the case of there is magnetic stimulation
Scatter distributions curve that multiple target areas in tested are associated, that detect enters with reference to hemozoin details in a play not acted out on stage, but told through dialogues scattered information
Row compares.At 1714, produce this compare comprise use circuit will use in the case of there is magnetic stimulation Lay because of Burger photograph
Scatter distributions curve that bright configuration obtains, that detect compares because of Burger illumination spectrum information with reference hemozoin Lay
Relatively.
At 1720, method 1700 comprises and is based in part on this and compares and magnetically disturb the malaria in this biological tissue
Protozoon pigment nanoparticle.At 1722, the magnetically hemozoin nanoparticle attached bag in one biological tissue of interference
Containing applying a magnetic stimulation, the feature of this magnetic stimulation and persistent period are sufficient so that the plasmodium in a biological tissue
Pigment nanoparticle affects the integrity of the digestibility food vacuole of malarial parasite.At 1724, magnetically interference one
Hemozoin nanoparticle in biological tissue comprises one alternating magnetic field of applying to stimulate, the feature that this alternating magnetic field stimulates with
And the hemozoin nanoparticle that is sufficient so that in a biological tissue of persistent period destroys the digestibility food of malarial parasite
The film of thing bubble.At 1726, magnetically the hemozoin nanoparticle in one biological tissue of interference comprises applying one
Individual time-varying magnetic field stimulates, and feature and persistent period that this time-varying magnetic field stimulates are sufficient so that parasitemia level and reduce.
Figure 18 show the example of the method 1800 for regulating plasmodium parasitism activity.At 1810, method 1800 is wrapped
Containing inquiring after multiple volume of focus and draw from the hemozoin in a biological tissue by stimulating with pulse electromagnetic energy
The non-linear multiple-harmonic response of nanoparticle, this pulse electromagnetic energy stimulates the peak value spoke with less than about 200 m. gigawatt (GW)s/cm^2
Illumination and have at least one the peak emission wavelength from about 690 nanometers to about 2100 nanometers, this pulse electromagnetic energy stimulates
Feature and the persistent period be enough to regulate the biological activity of the malaria infection factor.At 1812, draw from one biological group
The non-linear multiple-harmonic respond packet of the hemozoin nanoparticle knitted is irradiated in the plurality of volume of focus containing with electromagnetic energy
One or more interior biological tissue in hemozoin nanoparticle, this electromagnetic energy has from about 1000 nanometers
Peak emission wavelength to about 1300 nanometers.At 1814, draw from the hemozoin nanoparticle in a biological tissue
The non-linear multiple-harmonic respond packet of son is containing irradiating one or more the interior life in the plurality of volume of focus with electromagnetic energy
Hemozoin nanoparticle in fabric texture, this electromagnetic energy has from about 1000 nanometers to the peak emission of about 1080 nanometers
Wavelength.At 1816, draw the non-linear multiple-harmonic respond packet from the hemozoin nanoparticle in a biological tissue
Receive containing the hemozoin irradiated in one or more the interior biological tissue in the plurality of volume of focus with electromagnetic energy
Rice corpuscles, this electromagnetic energy has from about 1012 nanometers to the peak emission wavelength of about 1060 nanometers.At 1818, draw from
The non-linear multiple-harmonic respond packet of the hemozoin nanoparticle in one biological tissue is containing irradiating the plurality of with electromagnetic energy
The hemozoin nanoparticle in one or more interior biological tissue in volume of focus, this electromagnetic energy has about
The peak emission wavelength of 1040 nanometers.At 1820, draw from the hemozoin nanoparticle in a biological tissue
Non-linear multiple-harmonic respond packet is containing irradiating one or more interior one biological group in the plurality of volume of focus with electromagnetic energy
Hemozoin nanoparticle in knitting, this electromagnetic energy has from about 700 nanometers to the peak emission wavelength of about 870 nanometers.
At 1822, draw the non-linear multiple-harmonic respond packet from the hemozoin nanoparticle in a biological tissue and contain electricity consumption
Magnetic energy irradiates the hemozoin nanoparticle in one or more the interior biological tissue in the plurality of volume of focus,
This electromagnetic energy has from about 750 nanometers to the peak emission wavelength of about 810 nanometers.At 1824, draw from a biology
The non-linear multiple-harmonic respond packet of the hemozoin nanoparticle in tissue irradiates the plurality of volume of focus containing with electromagnetic energy
In one or more interior biological tissue in hemozoin nanoparticle, this electromagnetic energy has to be received from about 760
Rice is to the peak emission wavelength of about 780 nanometers.At 1826, draw from the hemozoin nanoparticle in a biological tissue
The non-linear multiple-harmonic respond packet of son is containing irradiating one or more the interior life in the plurality of volume of focus with electromagnetic energy
Hemozoin nanoparticle in fabric texture, this electromagnetic energy has the peak emission wavelength of about 780 nanometers.At 1828,
Draw the non-linear multiple-harmonic respond packet from the hemozoin nanoparticle in a biological tissue containing shining with electromagnetic energy
Penetrate the hemozoin nanoparticle in one or more the interior biological tissue in the plurality of volume of focus, this electromagnetic energy
The feature of amount and persistent period make a part for the hemozoin nanoparticle in a biological tissue produce non-linear
Multiple-harmonic responds, and the response of this non-linear multiple-harmonic has from about 233 nanometers to the wavelength of about 434 nanometers.At 1830, extract
The non-linear multiple-harmonic respond packet of the hemozoin nanoparticle in a biological tissue is many containing irradiating this with electromagnetic energy
The hemozoin nanoparticle in one or more interior biological tissue in individual volume of focus, the spy of this electromagnetic energy
Levy and the persistent period makes a part for the hemozoin nanoparticle in a biological tissue produce non-linear multiple-harmonic
Response, the response of this non-linear multiple-harmonic has from about 175 nanometers to the wavelength of about 325 nanometers.
At 1832, draw the non-linear multiple-harmonic from the hemozoin nanoparticle in a biological tissue and respond
Comprise and irradiate the hemozoin in one or more the interior biological tissue in the plurality of volume of focus with electromagnetic energy
Nanoparticle, the feature of this electromagnetic energy and persistent period make the hemozoin nanoparticle in a biological tissue
A part produces the response of non-linear multiple-harmonic, and the response of this non-linear multiple-harmonic has from about 175 nanometers to the ripple of about 290 nanometers
Long.At 1834, draw the non-linear multiple-harmonic respond packet from the hemozoin nanoparticle in a biological tissue and contain
Second harmonic sound is drawn by inquiring after the hemozoin nanoparticle in a biological tissue with the stimulation of pulse electromagnetic energy
Should, one or more in third harmonic response or the 4th harmonic response, the response of this second harmonic of being drawn, third harmonic ring
Should and the 4th harmonic response in one or more feature and the persistent period be adequate to bring about the program of an infectious agent
Sexual cell is dead.At 1836, draw the non-linear multiple-harmonic from the hemozoin nanoparticle in a biological tissue
Respond packet is containing inquiring after the hemozoin nanoparticle in a biological tissue and draw the by stimulating with pulse electromagnetic energy
One or more in the response of two harmonic responses, third harmonic or the 4th harmonic response, this second harmonic of being drawn response, the
One or more feature in three harmonic responses and the 4th harmonic response and persistent period be adequate to bring about with infect because of
The apoptosis of one host cell of son.At 1838, draw from the hemozoin nanoparticle in a biological tissue
The non-linear multiple-harmonic respond packet of son stimulates containing applying an electromagnetic energy, the intensity of this electromagnetic energy stimulation and persistent period
Be enough to cause the hemozoin nanoparticle in a biological tissue in a biological specimen to produce antimicrobial energy.1840
Place, draws the non-linear multiple-harmonic respond packet from the hemozoin nanoparticle in a biological tissue and contains one electricity of applying
Magnetic energy stimulates, and intensity and persistent period that this electromagnetic energy stimulates be enough to cause a non-linear multiple-harmonic response, and this is non-
Feature and the persistent period of linear multiple-harmonic response be enough to suppress the propagation of the malaria infection factor.At 1842, draw from
The non-linear multiple-harmonic respond packet of the hemozoin nanoparticle in one biological tissue is containing irradiating the plurality of with electromagnetic energy
The hemozoin nanoparticle in one or more interior biological tissue in volume of focus, this electromagnetic energy have from
The resolution [0.61* (peak emission wavelength/numerical aperture)] of about 300 nanometers to about 10 microns.
Figure 19 show the example of anti-malarial therapy method 1900.At 1910, method 1900 comprises in response to determining
There is hemozoin nanoparticle in biological specimen and apply electromagnetic energy and stimulate, the intensity that this electromagnetic energy stimulates with
And the hemozoin nanoparticle that the persistent period be enough to cause in a biological specimen produces an in vivo antimicrobial energy thorn
Swash.At 1912, applying electromagnetic energy stimulation and comprise one electromagnetic energy stimulation of delivery, the stimulation of this electromagnetic energy has less than about
200 m. gigawatt (GW)s/cm^2 is to the peak irradiance of less than about 200 m. gigawatt (GW)s/cm^2.At 1914, apply electromagnetic energy and stimulate bag
Containing delivering a pulse duration, this pulse duration has the femtosecond pulse frequency of about 8 megahertzs, receives from about 690
Rice is to the peak emission wavelength of about 2100 nanometers and from the resolution [0.61* (peak emission of about 300 nanometers to about 10 micron
Wavelength/numerical aperture)].At 1916, applying electromagnetic energy stimulation comprises generation to be had from 1200 nanometers to about 1300 nanometers
The electromagnetic energy of peak emission wavelength stimulates.At 1918, applying electromagnetic energy stimulation comprises generation to be had from 700 nanometers to about
The electromagnetic energy of the peak emission wavelength of 1000 nanometers stimulates.
Being desirably integrated at least partially in a data handling system of device described herein and/or process.Data
Processing system generally comprises one or more in the following: system unit shell, video display device, the most volatile
Property or the processor 404 of the memorizer of nonvolatile memory, such as microprocessor or digital signal processor, such as operate system
The calculating of system, driver, graphical user interface and application program interactive device individual, one or more (such as, touch pad,
Touch screen, antenna etc.), and/or comprise feedback circuit and control motor control system (such as, be used for detecting position
And/or the feedback of speed, for moving and/or adjust the control motor of assembly and/or quantity).Data handling system is permissible
Utilize suitable commercially available assembly to implement, such as generally calculate/communicate in data and/or institute in network calculations/communication system
Those assemblies seen.
As shown in example 1, with the nonlinear optical response information that such as hemozoin nanoparticle is associated, spectrum
Information or similar information can by one or more in vivo or in vitro techniques or methods determine.
Example 1: the in vivo analysis of hemozoin nanoparticle
The non-linear multiple-harmonic response energy of a kind of material for detection with hemozoin nanoparticle is described
The method of matter.Analyzing to carry out this, being crushed by the hemozoin crystal of synthesis becomes fine powder, and with volume ratio for five
Part isopropanol is suspended in isopropanol than a hemozoin crystal.By one of hemozoin/isopropanol suspension
Drop is positioned on quartz cover plate (0.25mm is thick), and allows isopropanol evaporate to produce hemozoin thin film.Exist further
By hemozoin film heating one minute to eliminate any remaining concentrated solution at 70 DEG C.From the amplification of 20 times to 100 times
Hemozoin perfection of crystal in this hemozoin thin film of lower assessment and distribution.Hemozoin thin film is observed
To the size of crystal be from less than 1 micron to about 10 to 20 micron.
Use the experimental configuration of general introduction in Figure 20 that hemozoin thin film is exposed to pulse electromagnetic energy to stimulate to draw
Nonlinear optical response from hemozoin nanoparticle.This experimental configuration use one in order to scan from 690 to
The Ti of the wavelength of 1040nm: sapphire laser and optical parametric oscillator (OPO) provide and are in 690nm and arrive
Pulse electromagnetic energy in the total size of 1600nm stimulates.Quartzy cover plate containing hemozoin thin film is attached to one receive
Meter level positioning table, to allow along optical axis (z scanning) and to carry out scanned samples along lateral surfaces (transversal scanning).Sample is put
It is placed between an achromatic objective (0.58 numerical aperture) and an achromatic condenser.One prism is used with filter system
Make spatial light filter to contain the peak emission wavelength from 175nm to 650nm.Spectrometer or photomultiplier tube is used to detect
Energy is responded from the non-linear multiple-harmonic of hemozoin particle.The various assemblies of experimental configuration are connected to a controller connect
Mouth (such as, computer), this control unit interface comprises Ti: sapphire laser, OPO, detector and nanoscale positioning table.
It is being designed to measure in one group of experiment that third harmonic responds, along optical axis (z scanning) and through having
The volume of focus of the excitation energy of 810nm scans hemozoin thin film.In this example, use has 0.9 numerical aperture
100 times of object lens.Third harmonic is responded energy and exciting light collimates so that it is through UG-11 stained glass light filter
(wavelength of transmission 250 to 350nm and 700 to 800nm) and 265nm groove (notch) light filter, and it is sent to photoelectricity
Multiplier tube.Directly measure the anode current from photomultiplier tube with electrometer, this electric current be converted to linearly a voltage,
And via data collecting card record on computers.Figure 21 A show and uses the method to carry out from hemozoin thin film
Representative z scanning.Also illustrate the comparison to quartz substrate to measure.The width at the peak in the case of two kinds is both less than 5 μm, and is less than
The beam size of 800nm is consistent (based on 100 times of object lens and 0.9 numerical aperture).Depend on the size of hemozoin crystal
And it being filled with the amount of the volume of focus of hemozoin, the value at hemozoin peak changes up to 20%.By first holding
Row z scanning analysis, to find maximum third harmonic response and to perform transversal scanning at this z location, also uses above-described ginseng
Number performs transversal scanning (Figure 21 B).Figure 22 show relative to the transversal scanning (2) in whole quartz substrate whole
The example of the third harmonic response of the transversal scanning (1) on hemozoin thin film.
Third harmonic response efficiency and square (A of spot sizespot 2) and square (τ of pulse width2) be inversely proportional to, and
And therefore monitoring the two variable and to make the two variable minimize be important.The diffractive technology of use standard knife-edge
It is distributed the volume of focus that pulse electromagnetic energy stimulates, in order to along optical axis in some positions measurement beam closing waist.Use
Autocorrelator carrys out the pulse width of measurement beam.Is contrasted by drawing laser excitation power P (ω) [mW] as illustrated in fig. 23
Three harmonic response power P (3 ω) [arbitrary unit] demonstrate to stimulate from pulse electromagnetic energy and power are output as three rank dependences
Property.The double-log drawing of these data produces slope and is about the straight line of 3.
Different assemblies that other assembly that what theme described herein illustrated sometimes is different is contained within or from different its
The different assemblies that its assembly connects.It will be appreciated that these frameworks described are only example, and indeed, it is possible to implement to realize
Other framework of the many of same functionality；In conceptual meaning, any assembly arrangement being used for realizing same functionality has
Effect ground " being associated ", thus realize needed for functional.Therefore, herein combined to realize any two of particular functionality
Regardless of framework or intermediate module how assembly can be viewed as each other " being associated ", thus functional needed for realizing,.With
Sample, any two assembly being so associated can also be considered each other " to operably connect " or " to operably
Couple " functional needed for realizing, and any two assembly that can be so associated can also be considered each other " can be with
Operable mode couples " with realize needed for functional.The instantiation that can couple to operably including (but not limited to)
The assembly that can coordinate physically and/or interact physically, and/or can be wirelessly mutual and/or with wireless parties
The assembly that formula interacts, and/or logically interact and/or can be the most mutual assembly.
Figure 23 A and 23B show in (Figure 23 A) lineal scale and (Figure 23 A) double-log scale the plasmodium drawn
3 rank power dependent of pigment.Figure 24 show the hemozoin 3 rank dependencies to incident power.Figure 25 is infected
The voxel image of the hemozoin crystal 2502 in erythrocyte 2504.Figure 26 show the red of infected and uninfection
The two-dimensional space scanning of blood cell, it is illustrated that corresponding to the intensity peak of the hemozoin crystal in infected cell.Shown in Figure 27
(THG) signal is produced for the third harmonic from the hemozoin nanoparticle suspended in water.Figure 28 show from malaria
The absolute third harmonic of protozoon pigment produces (THG) power, it is illustrated that 3 rank dependencies.Figure 29 show hemozoin-water
Three harmonic waves produce (THG) intensity.Figure 30 show the third harmonic become along with the wavelength originated and detect and produces (THG)
The two-dimensional graphics of signal.Figure 31 A show the malaria detection equipment 102c according to an embodiment.Figure 31 B is to use outside
The monitor of detection setting or the example of processing means.Figure 32 A show and uses third harmonic to produce the prison that (THG) detection is arranged
Survey device or the example of processing means.Figure 32 B show monitor or the process of the use dark field detection according to an embodiment
The example of device.
Figure 33 show malaria detection equipment 102c, wherein can implement one or more methods or technology, such as actively
Ground detection or process malaria infection.In one embodiment, malaria detection equipment 102c comprises a details in a play not acted out on stage, but told through dialogues indirect illumination and sets
Standby 3300, optical package 112 and a sensor cluster 440.In one embodiment, this malaria detection equipment
Comprising: an optical package 112, this optical package 112 has a sample side, a detector side and passes through
An optical axis；And a dark ground illuminator 3302, this dark ground illuminator is close to the sample side of optical package 112.
In one embodiment, dark ground illuminator 3302 comprises: an agent structure 3402, and this agent structure has many
Individual waveguide combination part 3406；And a sensor cluster 440, this sensor cluster comprises one or more sensor 442, this
Electromagnetic energy that a little sensors are configured to receive the sample that free dark ground illuminator 3302 inquires after, that be scattered.?
In one embodiment, the plurality of waveguide combination part 3406 is including at least a first electromagnetic energy radiator and one second
Electromagnetic energy radiator, in the intensity of illumination of this second electromagnetic energy radiator, peak emission wavelength or pulse frequency at least
One is different from this first electromagnetic energy radiator.In one embodiment, sensor cluster 440 comprises a sensor array
Row, for obtaining the electromagnetic energy scattered information depending on angle.In one embodiment, sensor cluster 440 comprises one
Individual sensor array, for obtaining the electromagnetic energy scattered information depending on wavelength.
Seeing Figure 33,34A and 34B, in one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises dark-ground illumination
Device 3302, this dark ground illuminator especially has an agent structure 3402 with aperture 3404 and multiple waveguide combination part
3406.In one embodiment, dark ground illuminator 3302 is configured at an optical axis relative to optical package 112
At one or more angle of incidence, electromagnetic energy is delivered at least one focal zone by multiple waveguide combination parts 3406.Citing
For, in one embodiment, the plurality of waveguide combination part 3406 is oriented in relative to optical package 112
At one or more angle of incidence of optical axis, electromagnetic energy is focused at least one focal zone.In one embodiment, secretly
Field illumination apparatus 3302 is configured around being substantially parallel to an axis of this optical axis and rotates.In one embodiment, secretly
Field illumination apparatus 3302 is configured at two or more azimuths relative to an optical axis of optical package 112 to be many
Individual electromagnetic energy beam is delivered on a focal zone.In one embodiment, dark ground illuminator 3302 is configured to two
At individual or more angle of incidence, electromagnetic energy is delivered on two or more focal zone position.
In one embodiment, the plurality of waveguide combination part 3406 comprises and is configured to be connected at least one electromagnetic energy
One or more electromagnetic energy waveguides 3408 of amount radiator 3410.For example, in one embodiment, the plurality of waveguide
One or more in molectron 3406 comprises at least one being configured to receive one or more electromagnetic energy waveguide 3408
Sleeve component 3412.In one embodiment, one or more in the plurality of waveguide combination part 3406 comprises and is configured to
Receive at least one sleeve component of one or more lens 3414, polariser 3416 and electromagnetic energy radiator 3410
3412。
In one embodiment, the plurality of waveguide combination part 3406 is axially distributed around aperture 3404.A reality
Executing in scheme, the plurality of waveguide combination part 3406 arranges around aperture 3404 with the pattern of one or more radial symmetric.One
In individual embodiment, the plurality of waveguide combination part 3406 arranges around aperture 3404 with one or more rotational symmetric patterns.
In one embodiment, the plurality of waveguide combination part 3406 is with the most right about the axis being substantially parallel to this optical axis
The one or more concentric pattern claimed arrange around aperture 3404.In one embodiment, the plurality of waveguide combination part 3406
Pacify around aperture 3404 with the one or more concentric pattern about the Axial-rotational Symmetry being substantially parallel to this optical axis
Row.In one embodiment, one or more in the plurality of waveguide combination part 3406 be configured in aperture 3404 right
Electromagnetic energy collimates.
In one embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one polariser
3416.In one embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one linear polarization.
In one embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one circular polarisers.One
In individual embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one adjustable polariser.
In one embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one lens
3414.In one embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one lens 3414, should
The electromagnetic energy that lens 3414 are configured to being radiated by this at least one electromagnetic energy radiator 3410 collimates.At one
In embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one lens 3414, and these lens are configured
The electromagnetic energy radiated by this at least one electromagnetic energy radiator 3410 for focusing.In one embodiment, the plurality of ripple
Lead at least one in molectron 3406 and comprise at least one microlens array.In one embodiment, the plurality of waveguide group
At least one in component 3406 comprises at least one planoconvex lens.In one embodiment, the plurality of waveguide combination part
At least one in 3406 comprises at least one non-spherical lens.
In one embodiment, to comprise at least one multifocal saturating at least one in the plurality of waveguide combination part 3406
Mirror.In one embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one zoom lens.One
In individual embodiment, at least one in the plurality of waveguide combination part 3406 comprises at least one liquid lens.An enforcement
In scheme, at least one in the plurality of waveguide combination part 3406 comprises at least one tunable liquid lens.A reality
Executing in scheme, at least one in the plurality of waveguide combination part 3406 comprises at least one liquid mirror.An embodiment party
In case, at least one in the plurality of waveguide combination part 3406 comprises the liquid mirror that at least one Electrowetting controls.
In one embodiment, electromagnetic energy radiator 3410 comprises one or more power radiation assembly 104.One
In individual embodiment, electromagnetic energy radiator 3410 comprises at least one in laser instrument, laser diode or light emitting diode.
In one embodiment, electromagnetic energy radiator 3410 comprise quantum dot, Organic Light Emitting Diode, tiny cavity light-emitting diode or
At least one in polymer LED.In one embodiment, electromagnetic energy radiator 3410 comprises at least one
Femtosecond laser.
In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprise for by details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 with
It is removably attached to the device of optical package 112.For example, in one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination sets
Standby 3300 comprise slip ring 3326, locking member 3328 and adapter 3330, for optical package 112 is connected to details in a play not acted out on stage, but told through dialogues
Illumination apparatus 3302.In one embodiment, for details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is removably attached to optics
The device of molectron 112 comprises a draw bail being positioned on details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300, and this draw bail is connected to
Corresponding draw bail on optical package 112.For example, in one embodiment, for details in a play not acted out on stage, but told through dialogues indirect illumination is set
Standby 3300 devices being removably attached to optical package 112 comprise a coupling member, and this coupling member has one
The individual surface defining an internal path, the size of this internal path and be sized to frictional fit at optical package
On the outer surface of 112.In one embodiment, for details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is removably attached to light
The device learning molectron 112 comprises bayonet socket draw bail, frictional fit draw bail, snap-fitted draw bail or thread connection
At least one in structure, these structures have one or more minor structure, and these minor structures are adapted to be and are connected to molectron
Corresponding bayonet socket draw bail, frictional fit draw bail, snap-fitted draw bail or thread joined structure on 112.?
In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 be configured to bayonet socket couple, frictional fit couple, snap-fitted
Couple or thread connection is removably attached to optical package 112.In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination sets
Standby 3300 comprise a draw bail, and this draw bail is configured to details in a play not acted out on stage, but told through dialogues indirect illumination equipment is attached to optical package
112.In one embodiment, this draw bail is configured to bayonet socket connection, frictional fit couples, snap-fitted connection
Or this details in a play not acted out on stage, but told through dialogues indirect illumination equipment is removably attached to optical package 112 by thread connection.
Seeing Figure 33, in one embodiment, optical package 112 especially comprises one or more optical package master
Body structure 3310, these optical package agent structures are connected to examine an end via one or more adapters 3312
Survey device 440 (such as, photoelectric detector, electromagnetic energy sensor, charge coupled device, video camera or the like).A reality
Executing in scheme, optical package 112 comprises at least one planoconvex lens 3314 and at least one lens keeps component 3316.?
In one embodiment, optical package 112 comprises at least one polariser 3318 and at least one polariser keeps component
3320.In one embodiment, optical package 112 comprises at least one and keeps component 3322, this holding component 3322 quilt
It is configured to be anchored in optical package agent structure 3310 lens assembly.In one embodiment, optics group
Component 112 comprises at least one objective lens component 3324.
In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises for along being substantially parallel to optical combination
One axis of one optical axis of part 112 adjusts the dark ground illuminator device 3304 relative to the distance of optical package 112.
In one embodiment, it is used for adjusting dark ground illuminator and comprises one relative to the device 3304 of the distance of optical package 112
Individual rotatably adjustable structure 3332, the size of this structure and be sized to couple a screwed part 3334.At one
In embodiment, comprise a details in a play not acted out on stage, but told through dialogues for adjusting dark ground illuminator relative to the device 3304 of the distance of optical package 112
Illumination apparatus fastening member 3333, this component is operable with the constraint rotation of dark ground illuminator 3302 or displacement.
Seeing Figure 34 B, in one embodiment, dark ground illuminator 3302 comprises multiple sensor 442 and multiple spy
Ask device.In one embodiment, the plurality of sensor 442 is configured to capture that free dark ground illuminator 3302 is inquired after
Individual sample, the electromagnetic energy that is scattered.In one embodiment, the plurality of each inquired after in device all comprises a ripple
Lead molectron 3406, this waveguide combination part comprise be configured to be connected to one of at least one electromagnetic energy radiator 3410 or
Multiple electromagnetic energy waveguides 3408, the plurality of device of inquiring after is oriented in one of an optical axis relative to an optical package
At individual or multiple angle of incidence, electromagnetic energy is focused at least one focal zone in this at least one aperture 3404.
In one embodiment, the plurality of inquire after device simultaneously or sequentially by least one first inquire after stimulation and
Inquiring after stimulation for one second to be directed on a focal zone, this second inquires after the intensity of illumination of stimulation, peak emission wavelength or arteries and veins
Rush at least one in frequency to be different from this and first inquire after stimulation.In one embodiment, the plurality of inquire after device simultaneously or
Sequentially inquire after stimulation to major general one first and one second inquire after stimulation and be directed on a focal zone, this second is inquired after
Stimulate to have and be different from this first angle of incidence inquiring after stimulation.In one embodiment, the plurality of device is inquired after simultaneously
Or sequentially to major general one first inquire after stimulation and one second inquire after stimulation and be directed on a focal zone, this second visit
Ask to stimulate to have and be different from this first peak emission wavelength inquiring after stimulation.In one embodiment, the plurality of inquire after device with
Time ground or sequentially inquire after stimulation to major general one first and one second inquire after stimulation and be directed on a focal zone, this is the years old
Two inquire after stimulation is different from this relative to the azimuth of an optical axis of an optical package and first inquires after stimulation.A reality
Executing in scheme, the plurality of device of inquiring after simultaneously or sequentially will inquire after stimulation offer to two at two or more angle of incidence
Or on more focal zone position.
In one embodiment, the multiple independent sensor in the plurality of sensor 442 couples to operably
Inquire after in device to the plurality of one or more, to form one or more sensor-inquire after device pair.For example, at one
In embodiment, form a sensor-inquire after device and the sensor of a part is arranged and is positioned an optical path
In, this optical path allows the capture of these sensors to be freely formed this sensor-inquire after device a part is inquired after device to be visited
The sample ask, the electromagnetic energy that is scattered, generally avoid not being scattered the electromagnetism of (such as, directly being reflected) simultaneously
Energy.In one embodiment, formed sensor-inquire after device be positioned as the sensor of a part only capturing from
By forming electromagnetic energy that a part is inquired after a sample that device inquired after by this sensor-inquire after device, that be scattered.One
In individual embodiment, the sensor of the part forming a sensor-inquire after device pair is positioned as missing and is directly reflected
Light and only capture be freely formed this sensor-inquire after device a part is inquired after a sample that device inquired after, through scattered
The electromagnetic energy penetrated.
In one embodiment, these sensors-inquire after devices is to being configured to from being inquired after by dark ground illuminator 3302
One sample acquisition depend on the electromagnetic energy scattered information of angle or depend on the electromagnetic energy scattered information of wavelength in extremely
Few one.For example, in one embodiment, the plurality of device of inquiring after is at an optical axis relative to an optical package
One or more angle of incidence at electromagnetic energy simultaneously or sequentially focused at least one focal zone of a sample.
In one embodiment, the one or more sensor-inquire after device is to obtaining the electromagnetic energy scattered information depending on wavelength.
In one embodiment, dark ground illuminator 3302 comprises multiple inquires after device and multiple sensor 442, and these inquire after device and biography
Sensor forms a part for an agent structure 3402 defining at least one aperture 3404.
In one embodiment, the plurality of each inquired after in device comprises a waveguide combination part 3406, this waveguide
Molectron 3406 has the one or more electromagnetic energy waves being configured to be connected at least one electromagnetic energy radiator 3410
Lead.In one embodiment, the plurality of waveguide combination part is oriented in an optical axis relative to an optical package
One or more angle of incidence at electromagnetic energy is focused at least one focal zone in this at least one aperture 3404.?
In one embodiment, dark ground illuminator 3302 comprises multiple sensor 442, and these sensors are configured to capture and are freely somebody's turn to do
The sample that dark ground illuminator 3302 is inquired after, the electromagnetic energy that is scattered.
See Figure 35, in one embodiment, for adjusting the dark ground illuminator distance relative to optical package 112
Device 3304 comprise one calculate device 402, this calculating device be connected to operably a rotatably adjustable structure,
One threaded adjustment structure or one slidably adjust at least one in structure.In one embodiment, device is calculated
402 are configured to via this rotatably adjustable structure, threaded adjustment structure or slidably adjust at least one in structure
Dark ground illuminator is actuated relative to optics group along the axis of an optical axis being substantially parallel to optical package 112
The displacement of component 112.
In one embodiment, for adjusting the dark ground illuminator device relative to the distance of optical package 112
3304 comprise at least one outside threaded loop configuration, and the threaded loop configuration in this outside is configured to use engagement thread
The loop configuration of one inner threaded of engagement, the loop configuration of this inner threaded is when being actuated with relative to this external belt spiral shell
The loop configuration of stricture of vagina makes dark ground illuminator 3302 along the optical axis being substantially parallel to optical package 112 when rotating
Article one, axis shifts relative to optical package 112.
In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises for adjusting by the plurality of electromagnetic energy waveguide
The device 3502 of the angle of incidence of the electromagnetic energy of molectron 3406 radiation.In one embodiment, for adjusting by the plurality of
The device 3502 of the angle of incidence of the electromagnetic energy of electromagnetic energy waveguide molectron radiation comprises at least one and calculates device 402, should
Calculate device and be connected to an electromechanical assembly, an opto-mechanical assembly, an electro-optical package or a sound to operably
At least one in optical assembly.In one embodiment, for adjusting by the radiation of the plurality of electromagnetic energy waveguide molectron
The device 3502 of the angle of incidence of electromagnetic energy comprises at least one and calculates device 402, and this calculating device couples to operably
To an electro-optic lens system.
In one embodiment, for adjustment entering by the electromagnetic energy of the plurality of electromagnetic energy waveguide molectron radiation
The device 3502 of firing angle comprises at least one and calculates device 402, and this calculating device is connected to one or more to operably
Tunable optical module.In one embodiment, for adjusting by the electricity of the plurality of electromagnetic energy waveguide molectron radiation
The device 3502 of the angle of incidence of magnetic energy comprises one and calculates device 402, and this calculating device is connected at least to operably
One optical waveguide, this optical waveguide is configured to change by one or more delivery in the plurality of waveguide combination part 3406
The angle of incidence of electromagnetic energy.In one embodiment, for adjusting by the electricity of the plurality of electromagnetic energy waveguide molectron radiation
The device 3502 of the angle of incidence of magnetic energy comprises one and calculates device 402, and this calculating device is connected at least to operably
One tunable liquid lens.In one embodiment, for adjusting by the radiation of the plurality of electromagnetic energy waveguide molectron
The device 3502 of angle of incidence of electromagnetic energy comprise one and calculate device 402, this calculating device is connected to operably
At least one optical micro prism.In one embodiment, for adjusting by the radiation of the plurality of electromagnetic energy waveguide molectron
The device 3502 of the angle of incidence of electromagnetic energy comprises one and calculates device 402, and this calculating device is connected to one to operably
Individual or multiple microlens arrays.
In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprise for adjust delivered by dark ground illuminator 3302
The device of angle of incidence of electromagnetic energy.In one embodiment, for adjusting the electromagnetism delivered by dark ground illuminator 3302
The device 3502 of the angle of incidence of energy comprises one and calculates device 402, and this calculating device is connected to a machine to operably
At least one in tool optical assembly, an electro-optical package or an acousto-optic assembly.In one embodiment, for adjusting by secretly
The device 3502 of the angle of incidence of the electromagnetic energy that illumination apparatus 3302 delivers comprises one and calculates device 402, this calculating device with
Operable mode is connected at least one optical waveguide, and this optical waveguide is configured to change by the plurality of waveguide combination part 3406
In one or more angle of incidence of electromagnetic energy delivered.In one embodiment, for adjusting by dark ground illuminator
The device 3502 of the angle of incidence of 3302 electromagnetic energies delivered comprises one and calculates device 402, and this calculating device is with operable side
Formula is connected at least one tunable liquid lens.In one embodiment, pass by dark ground illuminator 3302 for adjustment
The device 3502 of the angle of incidence of the electromagnetic energy sent comprises one and calculates device 402, and this calculating device couples to operably
To at least one optical micro prism.In one embodiment, for adjusting the electromagnetic energy delivered by dark ground illuminator 3302
The device 3502 of angle of incidence comprise one and calculate device 402, this calculating device is connected to one or more to operably
Microlens array.
In one embodiment, malaria detection equipment 102c is configured to detect the erythrocyte by malaria infection
And count.In one embodiment, malaria detection equipment 102c uses spectrum study to improve the quick of diagnosis in diagnosis
Perception and specificity.
In one embodiment, malaria detection equipment 102c comprises: an optical package 112, this optical package
112 have a sample side, a detector side and the optical axis passed through；One dark ground illuminator 3302, this is dark
Field illumination apparatus 3302 is close to the sample side of optical package 112；And for along being substantially parallel to optical package 112
An axis of an optical axis adjust the dark ground illuminator device 3304 relative to the distance of optical package 112.One
In individual embodiment, malaria detection equipment 102c comprise a detector 440, this detector 440 be configured to shooting with from
The sample inquired after by dark ground illuminator, one or more microphotograpies that the electromagnetic energy that is scattered is associated.A reality
Executing in scheme, malaria detection equipment 102c comprises one and is configured to fasten the object stage molectron for the sample analyzed.?
In one embodiment, dark ground illuminator 3302 comprises multiple waveguide combination part 3406, and a master with aperture 3404
Body structure 3402, this aperture 3404 is directed at along the axis being substantially parallel to an optical axis.An embodiment
In, electromagnetism that optical package 112 is configured to receive the sample that free dark ground illuminator 3302 inquires after, that be scattered
Energy.In one embodiment, malaria detection equipment 102c comprises and is configured to receive a biological specimen during operation
The sample stage molectron of chamber.In one embodiment, this sample stage molectron is configured to position along x, y or z direction
One biological specimen.In one embodiment, this sample stage molectron comprises a stepping motor, this stepping motor with
Operable mode is connected to one and calculates device 402 and be configured to position biological specimen chamber based on tiling scheme.
Seeing Figure 35, in one embodiment, system 100 especially comprises a testing circuit 3602, this testing circuit
It is configured to obtain one or more microphotograpies of a biological specimen at one or more visual fields.An embodiment
In, this testing circuit 3602 comprises one or more detector 440, and these one or more detectors are configured at one or many
At individual visual field and obtain one or more microphotograpies of a biological specimen at one or more depths of focus.
In one embodiment, system 100 comprises a resolution amendment circuit 3604, this resolution amendment circuit quilt
It is configured to revise the pixel counts of at least one microphotograph and produce at least one first modified microphotograph.One
In individual embodiment, this resolution amendment circuit 3604 comprises and is configured to revise one or many of microphotograph pixel resolution
Individual calculating device 402.In one embodiment, this resolution amendment circuit 3604 comprise at least one calculate device 402 with
And one or more data structure 424, these one or more data structures 424 are operable to produce and to store a threshold ratio
Relatively it is worth, and produces and store one based on this threshold comparison value for the multiple pixels forming a microphotograph are entered
The core (kernel) that row filters.
In one embodiment, system 100 comprises one and filters core generation circuit 3606, and this filtration core produces circuit quilt
It is configured to produce one for the multiple pixels forming this first modified microphotograph being entered based on a filtering feature
The core that row filters, and produce at least one the first Saliency maps picture representing this at least one modified microphotograph.
In one embodiment, system 100 comprises an Object identifying circuit 3608, and this Object identifying circuit is configured
In indicating in this at least one microphotograph in this first Saliency maps picture for identification, one or more objects of imaging are many
Individual pixel group, and produce the one or more connected ingredient of a curve chart, this graphical representation is at this at least
One microphotograph indicates multiple pixel groups of the object of these one or more imagings.In one embodiment, object
Identification circuit 3608 comprises a circuit, and this circuit is configured to identify in the instruction the following in this first Saliency maps picture
The pixel group of at least one: hemozoin nanoparticle in this at least one microphotograph, red by malaria infection
Blood cell or the erythrocyte of uninfection.In one embodiment, Object identifying circuit 3608 is configured to determine that this biology sample
This is by the probability of malaria infection, and determines the confidence level joined by probability correlation determined by malaria infection with this biological specimen
Level.
In one embodiment, system 100 comprises a circuit 3610, and this circuit is configured to this song produced
The one or more connected ingredient of line chart is entered with the references object information being stored in one or more data structure 424
Row compares, and one or more connected ingredient based on this curve chart produced and this references object information should
Relatively produce a response.In one embodiment, this is configured to or many of comparison this curve chart produced
The circuit 3610 of individual connected ingredient comprises one or more data structure 424, deposits in these one or more data structures
Containing references object information, this references object information comprises erythrocyte plot information, erythrocyte curve chart by malaria infection
At least one in information or hemozoin plot information.In one embodiment, this is configured to compare and is produced
The circuit 3610 of one or more connected ingredient of this curve chart comprise a circuit 3612, this circuit is configured to
Producing a response, this respond packet is containing at least one in the following: object identification information, morbid state, parasitemia
By erythrocyte and total erythrocytic ratio of malaria infection present in level, red-cell count, this at least one microphotograph,
Or the probability that is associated with an object identified and level of confidence information.
In one embodiment, system 100 comprises a spatial frequency and produces circuit 3614, and this spatial frequency produces electricity
Road 3614 is configured to determine that a spatial frequency spectrum of at least one the first pixel subgroup of this at least one microphotograph, should
This spatial frequency spectrum of first pixel subgroup with compare with reference to spatial spectral information, and based on this first pixel subgroup should
Spatial frequency spectrum relatively produces a response with this reference spatial spectral information.In one embodiment, spatial frequency is produced
Raw circuit 3614 comprises one or more data structure 424, and these data structures have with reference to erythrocyte spatial spectral information, ginseng
Examine by the erythrocyte spatial spectral information of malaria infection or with reference at least one in hemozoin spatial spectral information.One
In individual embodiment, spatial frequency produces circuit 3614 and is configured to use in cluster scheme or Learning Scheme at least
The spatial frequency spectrum of this at least the first pixel subgroup is divided into one or more information subgroup by one.An embodiment
In, this spatial frequency produce at least one that circuit 3614 is configured to use in the following by this at least the first
This spatial frequency spectrum of pixel subgroup is divided into one or more information subgroup: Fuzzy C meansigma methods cluster scheme, graph theory scheme, point
Layer cluster scheme, K meansigma methods cluster scheme, position sensing Hash scheme (Locality-Sensitive Hashing
Protocol), mixed Gaussian scheme, cluster scheme based on model, cluster weighting modeling scheme, expectation maximization scheme,
Principal component analysis scheme or splitting scheme.
In one embodiment, dark ground illuminator system comprises one and inquires after stimulation circuit and a testing circuit
3602.In one embodiment, inquire after stimulation circuit and be configured to be directed to electromagnetic energy stimulation one of one sample
Or in multiple volume of focus.In one embodiment, stimulation circuit is inquired after including at least a first electromagnetic energy radiator
3410 and a second electromagnetic energy radiator 3410, this second electromagnetic energy radiator 3410 has and is different from this first electricity
The peak emission wavelength of magnetic energy radiator 3410.
In one embodiment, testing circuit 3602 is configured at one or more angle of incidence obtain freely be somebody's turn to do
Electromagnetic energy that inquire after the sample that stimulation circuit inquired after, that be scattered.In one embodiment, testing circuit 3602
It is configured to inquiring after what stimulation circuit was inquired after relative to next free this of acquisition at one or more azimuths of an optical axis
One sample, the electromagnetic energy that is scattered.In one embodiment, this testing circuit 3602 comprises one or more detection
Device, these detectors are configured at one or more visual fields and at one or more depths of focus obtain free this and inquire after
The electromagnetic energy being scattered of the sample that stimulation circuit is inquired after.In one embodiment, testing circuit is configured to
Obtain freely this inquire after a sample that stimulation circuit inquired after, the electromagnetic energy scattered information that depends on wavelength.
Figure 37 show the example of method 3700.At 3710, method 3700 comprises one testing circuit of use and comes one
One or more microphotograpies of a biological specimen are obtained at individual or multiple visual field.At 3712, obtain the one of biological specimen
Individual or multiple microphotograpies comprise and at least shoot first microphotograph and a second micro-photograph based on tiling scheme
Sheet.At 3714, the one or more microphotograpies obtaining biological specimen are included in the biological sample of acquisition at one or more depth of focus
This one or more microphotograpies.
At 3720, method 3700 comprise at least one revised in these one or more microphotograpies resolution and
Produce at least one first modified microphotograph.At 3722, amendment microphotograph resolution comprises to be held microphotograph
The operation of Row sum-equal matrix size.At 3724, amendment microphotograph resolution comprises microphotograph execution potting gum
(binning) scheme.At 3726, amendment microphotograph resolution comprise execution one prioritization scheme, this prioritization scheme based on
One object detection scheme adjusts the size of the one or more pixels in this microphotograph.
At 3730, method 3700 comprise by based on a filtering scheme to this at least the first modified microphotograph
Carry out filtration and produce a first filtered microphotograph.At 3732, produce the first filtered microphotograph and comprise
One is filtered core and carries out convolution with one or more pixel-parameters being associated with this first modified microphotograph to produce
A raw filtered microphotograph.At 3734, produce the first filtered microphotograph and comprise and determine this at least the first warp
Whether the intensity of one or more pixels of the microphotograph of amendment meets a threshold value.At 3736, produce this first process
The microphotograph of filter comprises filtering this microphotograph core carry out convolution with at least partially.At 3738, producing should
First filtered microphotograph comprises and filters core and these one or more pixel-parameters by one and carry out convolution, and based on this
The result of convolution determines the multiple connected ingredient of a curve chart for multiple pixels.At 3740, producing should
First filtered microphotograph comprises and filters core and one or more pixel-parameters by one and carry out convolution, and produce with should
The probit image that first filtered microphotograph is associated.
At 3742, produce this first filtered microphotograph comprise use cluster scheme or Learning Scheme at least
This at least one microphotograph is divided into one or more pixel subgroup by one.At 3744, produce this first through filter
Microphotograph comprise and use at least one in the following to be divided into one or more by this at least one microphotograph
Pixel subgroup: Fuzzy C meansigma methods cluster scheme, graph theory scheme, layering cluster scheme, K meansigma methods cluster scheme, position sensing dissipate
The modeling scheme of row scheme, mixed Gaussian scheme, cluster scheme based on model, cluster weighting, expectation maximization scheme, main one-tenth
Divide analytical plan or splitting scheme.
At 3750, method 3700 comprises the object by identifying this biological specimen in this filtered microphotograph
Determine a kind of morbid state.At 3752, determine that this morbid state comprises and compare to identify by probit and threshold value index
Object in microphotograph.At 3754, determine that this morbid state comprises the ratio based on a probit image and threshold value index
Relatively determine the multiple connected composition portion of a curve chart of the contents of object represented in this first modified microphotograph
Point.At 3756, determine that this morbid state comprises the probability determining biological specimen by malaria infection.At 3758, determine this disease
Diseased state comprises and determines the level of confidence joined by a determined probability correlation of malaria infection with this biological specimen.3760
Place, determines that this morbid state comprises and is applied to show by Dole Ma Ge-Mendelsohn (Dulmage-Mendelsohn) decomposing scheme
Micro-photo at least some of to identify multiple connected ingredients.
At 3770, method 3700 is included at one or more depth of focus and obtains the one or more aobvious of a biological specimen
Micro-photo.At 3780, method 3700 comprises so that one or more microphotograpies of this acquired biological specimen being stored
In a physical data structure 424.
Example 2: detect the malaria in a biological specimen
Image Acquisition
Seeing Figure 38, in one embodiment, malaria detects equipment 102c from many visual fields to a biological specimen (example
As, blood sample) shooting microphotograph.In one embodiment, obtain microphotograph time by microphotograph from a biography
Sensor assembly 440 stream transmission is to one or more calculating devices 402, until the microphotograph being laid on this biological specimen
Till one defined pattern is completed by scan table.Each microphotograph is stored to storage device (such as, data
Structure 424) for the filing of medical diagnosis on disease and process, under sample is moved on a biological specimen by sample stage simultaneously
One imageable target.
Aulomatizeted Detect
In one embodiment, Aulomatizeted Detect and counting to infected cell are by multiple statistical methods
Combination realize, these statistical methods are by the confidence interval in infected for body one by one probability and parasitemia
(with the mark of blood cell of parasite) quantifies.
Find notable object
In one embodiment, by by potting gum or apply another kind of adjusted size of operation first to adjust this
The resolution of microphotograph, in order to the size of each pixel in optimization microphotograph is for object detection.An enforcement
In scheme, by malaria infection to as if by measuring what its light levels detected: infected cells show is not subject to for ratio
The cell infected is brighter.In one embodiment, t testing filters is applied to the microphotograph after being sized, with
Just the probability (null hypothesis) that a pixel is brighter unlike background is measured.A threshold value (such as, 0.01) is specified for null hypothesis,
Make all to can be regarded as any pixel with the p value less than null hypothesis threshold value one than background pixel notable brighter object.
In one embodiment, filter core and background pixel is defined as a district with certain size around tested pixel.Will
This core carries out convolution in whole microphotograph, and this filter can be presented as non-linear filter, to nonlinear images
The linear filter of intermediate, or the linear filter of microphotograph.In one embodiment, it is to non-by t test implementation
The linear filter of linear image intermedium, calculates speed to increase.
In one embodiment, pixel can be compared with the whole microphotograph as background distributions.But,
Carry out filtering the advantage that there is uniqueness with the core of certain mark with microphotograph size: laterally brightness is adaptive to little
It is intrinsic for core.Significance test about this core is insensitive for the change of the intensity of illumination on whole visual field, and
Also have ignored many objects bigger than desired target.
Object identifying
In one embodiment, multiple pixels can be significant for an erythrocyte in microphotograph,
And these pixels need to be identified as single object.In one embodiment, the curve chart of notable pixel it is determined by
Multiple connected ingredients identify object (such as, by the cell etc. of malaria infection).For example, to adjacency matrix
Dole Ma Ge-Mendelsohn decomposition is determined identifying unique notable pixel group.In one embodiment, found
Each ingredient being connected is probably a cell by malaria infection (having the p value returned by t test).
For specific spectrum screening
In order to improve the specificity of diagnosis, in one embodiment, (such as, empty by performing the spectrum to microphotograph
Between frequency) analyze make false positive results minimum.For example, in one embodiment, for each notable object,
From the microphotograph of original (unjustified size), select multiple windows with different size of pixel region, and determine fast
Speed Fourier transform is to produce the spectrum signature of each object.In one embodiment, by object spectrum with stored from
Previously the template in the spectrum storehouse of the object through analyzing compared.In one embodiment, this storehouse comprise known infected carefully
Many samples of born of the same parents, the infected cell of detection automatically, and a large amount of tester, such as dust, scratch, fingerprint, healthy blood,
Defocus, defective illumination etc..Use statistical test by the spectrum of each object and from the one in the reference spectrum in this storehouse
Or many persons compares, in order to calculate the probability that spectrum signature is identical.In one embodiment, the threshold value (two of null hypothesis is applied
Individual spectrum has identical distribution) screen object, and select those objects consistent with the characteristic of infected cell.At spectrum sieve
In one embodiment of choosing, various coordinate systems are integrated 2D FFT, right to obtain on x, y, radial direction and angle direction
The power spectrum of elephant.These power spectrum are actually in microphotograph the probability density letter of the Energy distribution in whole spatial frequency
Number.Application Andrei Kolmogorov-Vladimir Smirnov (Komolgorov-Smirnov) test is to calculate to enter with the reference spectrum in storehouse
The null hypothesis of each power spectrum that row compares.In another embodiment, by 2D object spectrum and the 2D reference spectrum in storehouse
Crosscorrelation performs template matching.Again, application significance test is matched with from storehouse to measure object spectrum
The probability of spectrum.
Diagnosis
In one embodiment, after Object identifying and spectrum screening, together with the p value one that is associated of each object
Rise, only the satisfied object as the threshold probability of infected cell is counted.In one embodiment, together with being calculated
Go out, the most infected probability of this individuality comes together to produce the diagnosis of infected/uninfection.An embodiment
In, produce respond packet and report the number of infected cell containing the ratio as infected cell Yu total cell, wherein to this ratio
The confidence interval of rate is 95%.
Spectroscopy in template base is practised
In one embodiment, a process identification circuit contains and has the multiple of known identities under controlled conditions
The storehouse of object.In one embodiment, process the microphotograph of infected cell, and it is notable to confirm that spectrum is saved in storehouse
The identity of object.In one embodiment, process the microphotograph of uninfection sample, and be saved in storehouse for refusal
The positive findings of mistake is from without counting the positive findings of these mistakes diagnosis report.In one embodiment, will
Spectrum information from treated microphotograph is stored in one to be had and is associated in the data structure storehouse of p value.Right according to one
As spectrum belongs to the probability of the storehouse classification (such as, dust particle etc.) assigned to by template matching process, use multiple weight
Calculate variance and the meansigma methods of storehouse spectrum.
Multi dimensional object identification
In one embodiment, by using an object stage being scanned in 3 dimensions, and z-axis is added
For focusing on, it is possible to obtain about more spatial informations of an object.For example, by moving focal plane and can shoot
The object that one the most smooth is different from the most spherical object with same radius by another microphotograph.Process identification
An Additional embodiments be in the sample from identical visual field in different focal planes at shoot two or more than two aobvious
Micro-photo.In one embodiment, in the situation of the some scattering function being aware or unaware that the 3-dimensional shape for reconstructing object
The deconvolution of lower execution microphotograph stacking.Equally, apply the template matching to a storehouse, but be now in more various dimensions
Application.In one embodiment, by adding a dimension for optical wavelength, can will be associated with monochromatic microphotograph
Method be applied to color photomicrography.Spectrum point can be performed in Spatial Dimension and optical wavelength dimension subsequently by compound mode
Analysis.
In one embodiment, one or more assemblies may be referred to as " being configured to " herein, " can be configured
For ", " operable/operation with ", " be adapted/can be adaptive ", " can ", " may conform to/accord with " etc..These terms are (such as,
" it is configured to ") can generally contain the assembly of active state and/or the assembly of inactive state and/or the group of resting state
Part, unless requirement additionally made in context.
Foregoing detailed description set forth each of device and/or process by using block diagram, flow chart and/or example
Plant embodiment.So far, these block diagrams, flow chart and/or example contain one or more function and/or operation, reader
It is to be understood that each function and/or operation in these block diagrams, flow chart and/or example can be by broad range of
Hardware, software, firmware or almost its any combination individually and/or collectively implement.Additionally, use " beginning " in block diagram,
" terminate " or " stopping " frame is not configured to indicate the restriction starting or terminating to any function in figure.Can be by these flow processs
Figure or figure are incorporated in other flow chart or figure, in these other flow chart or figure, shown in the figure of the application
Extra function is performed before or after function.In one embodiment, if the stem portion of theme described herein can be through
By special IC (ASIC), field programmable gate array (FPGA), digital signal processor (DSP) or other integrated form
Implement.But, entirety or a part in terms of some of the embodiment disclosed herein can the most in integrated circuits
The one or more computer programs being embodied as running on one or more computers are (such as, at one or more computers
In system run one or more programs), on one or more processors 404 run one or more programs (such as,
The one or more programs run on one or more microprocessors), firmware or above every substantially any combination, and
According to this disclosure, design circuit and/or to write the code for software and/or firmware will be those skilled in the art
Understand completely.It addition, the mechanism of theme described herein can be distributed as program product in a variety of forms, and nothing
Opinion is used for how actually carrying out the particular type of the signal bearing media of this distribution, the illustrative enforcement of theme described herein
Scheme is all suitable for.The limiting examples of signal bearing media comprises the following: recordable type media, such as soft magnetism
Dish, hard disk drive, compact disk (CD), digital video disks (DVD), digital magnetic tape, computer storage etc.；And
The media of transport-type, such as numeral and/or analogue communication media (such as, fiber optic cables, waveguide, wired communications links, wireless
Communication link (such as, emitter, receptor, transceiver, transmitting logic, reception logic etc.) etc.).
Although having illustrated and described the particular aspects of invention described herein theme, but reader will appreciate that, based on
This paper teaches content, can make a change and repair in the case of without departing from theme described herein and relative broad range thereof
Change, and therefore, appended claims will contain the true spirit and model that belong to theme described herein in the range of it
Enclose interior all these changes and amendment.Generally, herein and especially in appended claims (such as, appended power
Profit claim main body) in use term the most set be that (such as, term " comprises " and should solve as " open " term
Be interpreted as " including but not limited to ", term " has " and should be construed to " at least having ", term " include " being construed to " include but
It is not limited to " etc.).If additionally, be intended to a given number of introduced claims state thing, then will want in right
State this scope in asking clearly, and in the case of there is not this statement thing, there is not this scope.For example, in order to
Helping to understand, appending claims may use introductory phrase " at least one " and " one or more " to introduce
Claims state thing.But, the use of these phrases is not construed as hint and is situated between by indefinite article "a" or "an"
The claims state thing continued requires any specific rights of the claims state thing introduced containing this all to limit
In containing only the claim of one this kind statement thing, even if comprising introductory phrase " one or more " when same claim
Or be also that so (such as, " one " and/or " one " is usual during the indefinite article such as " at least one " and such as "a" or "an"
" at least one " or " one or more " should be construed as to imply that)；For being used for introducing the definite article of claims state thing
Use, situation is also such.Even if it addition, state the given number of a claims state thing introduced clearly,
This statement thing also should be typically interpreted to mean at least this statement thing number (such as, do not have other modifier " two old
State thing " plain statement generally mean that at least two state thing, or two or more statement things).Additionally, using class
In those examples of the convention being similar to " at least one in A, B and C ", generally this kind structure is in the sense that this convention
It is set that (such as, " system of an at least one having in A, B and C " will be including but not limited to individually having A, individually
There is B, individually there is C, jointly there is A and B, jointly there is A and C, jointly there is B and C and/or there is A, B jointly
And the system of C etc.).In those examples of the convention being similar to " at least one in A, B or C etc. " in use, generally
This kind of structure is set (such as, " system of an at least one having in A, B or C " general bag in the sense that this convention
Containing but be not limited to individually to have A, individually there is B, individually there is C, jointly there is A and B, jointly there is A and C, jointly have
There is B and C and/or there is the system of A, B and C etc. jointly).Generally, either still illustrate at description, claims
In, the separation property word and/or the phrase that present two or more selectivity terms all should be understood to take into account comprise this
One in a little terms, any one in these terms or the probability of the two term, unless regulation additionally made in context.
For example, phrase " A or B " will be generally understood as comprising " A " or " B " or the probability of " A and B ".
About appended claims, the operation wherein stated generally can perform with any order.And, although
It is to present various operating process in order, it is to be understood that various behaviour can be performed with the order being different from illustrated order
Make, or can simultaneously perform various operation.These examples substituting order can comprise overlap, staggered, that interrupt,
That reorder, that be incremented by, that prepare, supplementary, simultaneously, reversing or the order of other change, unless context additionally does
Go out regulation.Additionally, such as " in response to ", " relating to " or the adjectival term of other past tense be generally not intended to get rid of these
Modification, unless regulation additionally made in context.
Although the most having disclosed various aspect and embodiment, but other aspect and embodiment also having allowed for
's.The purpose that the various aspects disclosed herein and embodiment illustrate that, and be not intended to limit, Qi Zhongzhen
Real scope and spirit are indicated by appended claims.
Claims (31)
1. a details in a play not acted out on stage, but told through dialogues indirect illumination equipment, including:
One dark ground illuminator, comprises
One agent structure, this agent structure has an aperture and multiple waveguide combination part, the plurality of waveguide combination part bag
Containing being configured to be connected to one or more electromagnetic energy waveguides of at least one electromagnetic energy radiator, and the plurality of waveguide
Molectron be oriented in relative at one or more angle of incidence of an optical package optical axis by electromagnetic energy
Focus at least one focal zone in this aperture；And
For adjusting a dark ground illuminator along an axis of the optical axis being substantially parallel to this optical package
Device relative to the distance of an optical package.
2. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, is wherein used for adjusting this dark ground illuminator relative to a light
The device of the distance learning molectron comprises one and calculates device, and this calculating device is connected to a rotatable tune to operably
Whole structure, a threaded adjustment structure or one slidably adjust at least one in structure, and this calculating device is configured to
Via this rotatably adjustable structure, this threaded adjustment structure or this slidably to adjust at least one in structure dark to actuate this
Illumination apparatus relative to an optical package along an axis of the optical axis being substantially parallel to this optical package
Carry out displacement.
3. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, wherein this dark ground illuminator is configured to relative to one
At two or more azimuths of one optical axis of optical package, a plurality of electromagnetic energy beam is delivered in this aperture
On one focal zone.
4. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, wherein this dark ground illuminator is configured at two or more
At individual angle of incidence, electromagnetic energy is delivered on two or more focal zone position.
5. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, at least one in the most the plurality of waveguide combination part comprises
At least one polariser.
6. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, farther includes:
For adjusting the device of an angle of incidence of the electromagnetic energy delivered by this dark ground illuminator.
7. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 6, wherein for adjusting the electromagnetism delivered by this dark ground illuminator
The device of this angle of incidence of energy comprises one and calculates device, and this calculating device is connected to a mechanical optics to operably
At least one in assembly, an electro-optical package or an acousto-optic assembly.
8. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 6, wherein for adjusting the electromagnetism delivered by this dark ground illuminator
The device of this angle of incidence of energy comprises one and calculates device, and this calculating device is connected at least one optics to operably
Waveguide, this optical waveguide is configured to change the one of the electromagnetic energy delivered by one or more in the plurality of waveguide combination part
Individual angle of incidence.
9. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, farther includes:
One draw bail, this draw bail is configured to this details in a play not acted out on stage, but told through dialogues indirect illumination equipment is removably attached to one
Optical package.
10. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 9, wherein this draw bail is configured to a bayonet socket connection
Connect, frictional fit couples, a snap-fitted connection or thread connection by this details in a play not acted out on stage, but told through dialogues indirect illumination equipment with can
Dismounting mode is attached to this optical package.
11. 1 kinds of malaria detection equipment, including:
One optical package, this optical package has a sample side, a detector side and one passed through
Optical axis；
One dark ground illuminator, this dark ground illuminator is close to this sample side of this optical package, and this dark ground illuminator comprises
Multiple waveguide combination parts, and
One agent structure, this agent structure has an aperture, and this aperture is along being substantially parallel to of an optical axis
Axis is directed at；
For adjusting a dark-ground illumination along an axis of the optical axis being substantially parallel to an optical package
Device is relative to the device of the distance of this optical package；
Electromagnetic energy that this optical package is configured to receive the sample that freely this dark ground illuminator is inquired after, that be scattered
Amount；And
One detector, this detector is configured to shooting and that carry out this sample that freely this dark ground illuminator is inquired after, this warp dissipate
One or more microphotograpies that the electromagnetic energy penetrated is associated.
12. 1 kinds of equipment for detection, including:
One dark ground illuminator, has
One agent structure, this agent structure defines at least one aperture,
Multiple inquiring after device, these are inquired after device and each include a waveguide combination part, and this waveguide combination part comprises and is configured to couple
To one or more electromagnetic energy waveguides of at least one electromagnetic energy radiator, the plurality of inquire after device be oriented in relative to
Electromagnetic energy is focused in this at least one aperture at one or more angle of incidence of one optical axis of one optical package
At least one focal zone on；And
Multiple sensors, these sensors be configured to capture the sample that freely this dark ground illuminator is inquired after, through dissipating
The electromagnetic energy penetrated.
13. equipment as claimed in claim 12, the multiple independent sensor in the most the plurality of sensor is with operable side
Formula be connected to the plurality of inquire after in device one or more, to form one or more sensor-inquire after device pair.
14. equipment as claimed in claim 13, wherein this one or more sensors-inquire after device depends on angle to obtaining
Electromagnetic energy scattered information or at least one in depending on the electromagnetic energy scattered information of wavelength.
15. equipment as claimed in claim 13, the multiple independent sensor in the most the plurality of sensor is positioned one
In light path, this light path generally avoids not from the electromagnetic energy of sample scatter, and this sample is by forming these sensors-inquire after
A part for device pair the plurality of inquire after in device one or more inquire after.
16. equipment as claimed in claim 12, the most the plurality of device of inquiring after is at a light relative to an optical package
Simultaneously or sequentially electromagnetic energy is focused at one or more angle of incidence of axle at least in this at least one aperture
On individual focal zone.
17. equipment as claimed in claim 12, the most the plurality of inquire after device simultaneously or sequentially by least one first visit
Ask stimulate and one second inquire after stimulation and be directed on a focal zone, this second inquire after stimulation have be different from this first visit
Ask the angle of incidence stimulated.
18. equipment as claimed in claim 12, the most the plurality of inquire after device simultaneously or sequentially by least one first visit
Ask stimulate and one second inquire after stimulation and be directed on a focal zone, this second inquire after stimulation have be different from this first visit
Ask the peak emission wavelength stimulated.
19. equipment as claimed in claim 12, the most the plurality of device of inquiring after simultaneously or sequentially enters at two or more
Stimulation offer is inquired after to two or more focal zone position by multiple at firing angle.
20. equipment as claimed in claim 12, farther include:
For adjusting a dark-ground illumination along an axis of the optical axis being substantially parallel to an optical package
Device is relative to the device of the distance of this optical package；And
For adjusting the device of an angle of incidence by the plurality of electromagnetic energy inquiring after device radiation.
21. 1 kinds of malaria detection equipment, including:
One optical package, this optical package has a sample side, a detector side and one passed through
Optical axis；And
One dark ground illuminator, this dark ground illuminator is close to this sample side of this optical package, and this dark ground illuminator comprises
Multiple waveguide combination parts,
One sensor cluster, this sensor cluster comprises one or more sensor, and these one or more sensors are configured
For electromagnetic energy that receive the next freely sample that this dark ground illuminator is inquired after, that be scattered；And
One agent structure, this agent structure has at least one aperture, and this at least one aperture is along being substantially parallel to this
One axis alignment of one optical axis of optical package.
22. malaria as claimed in claim 21 detection equipment, farther include:
For adjusting a dark ground illuminator along an axis of the optical axis being substantially parallel to this optical package
Device relative to the distance of this optical package.
23. malaria as claimed in claim 21 detection equipment, farther include:
For adjusting the device of an angle of incidence of the electromagnetic energy delivered by this dark ground illuminator.
24. malaria as claimed in claim 21 detection equipment, farther include:
One detector, this detector is configured to shooting and that carry out this sample that freely this dark ground illuminator is inquired after, this warp dissipate
One or more microphotograpies that the electromagnetic energy penetrated is associated.
25. 1 kinds of dark ground illuminators, including:
One agent structure, this agent structure defines at least one aperture；
Multiple inquiring after device, these are inquired after device and each include a waveguide combination part, and this waveguide combination part comprises and is configured to couple
To one or more electromagnetic energy waveguides of at least one electromagnetic energy radiator, the plurality of inquire after device be oriented in relative to
Electromagnetic energy is focused in this at least one aperture at one or more angle of incidence of one optical axis of one optical package
At least one focal zone on；And
Multiple sensors, these sensors be configured to capture the sample that freely this dark ground illuminator is inquired after, through dissipating
The electromagnetic energy penetrated.
26. dark ground illuminators as claimed in claim 25, the most the plurality of sensor is connected to the plurality of to operably
That inquires after in device multiple independent inquires after device, and is configured to obtain the electromagnetic energy scattered information depending on angle.
27. dark ground illuminators as claimed in claim 25, the most the plurality of sensor is connected to the plurality of to operably
That inquires after in device multiple independent inquires after device, and is configured to obtain the electromagnetic energy scattered information depending on wavelength.
28. dark ground illuminators as claimed in claim 25, farther include:
One draw bail, this draw bail is configured to a bayonet socket connection, frictional fit connection, a hasp
Coordinate connection or a thread connection that this dark ground illuminator is removably attached to an optical package.
29. 1 kinds of dark ground illuminator systems, including:
Inquiring after stimulation circuit for one, this inquires after stimulation circuit including at least a first electromagnetic energy radiator and one second
Electromagnetic energy radiator, this inquire after stimulation circuit be configured at one of an optical axis relative to an optical package or
At multiple angle of incidence, an electromagnetic energy is stimulated and be directed in one or more volume of focus of a biological specimen, wherein should
Optical package has a sample side, a detector side and the described optical axis passed through, and this is inquired after stimulation circuit and connects
It is bordering on this sample side of this optical package；And
One testing circuit, this testing circuit is configured at one or more angle of incidence obtain free this and inquires after stimulation electricity
The biological specimen that road is inquired after, the electromagnetic energy that is scattered.
30. dark ground illuminator systems as claimed in claim 29, wherein this testing circuit is relative to this optical package
Article one, at one or more azimuths of optical axis, obtain freely that this inquires after a biological specimen that stimulation circuit inquired after, warp
The electromagnetic energy of scattering.
31. dark ground illuminator systems as claimed in claim 29, wherein this testing circuit comprises one or more detector, uses
With obtain at one or more visual fields and at one or more depths of focus freely this inquire after that stimulation circuit is inquired after one
Individual biological specimen, the electromagnetic energy that is scattered.
Applications Claiming Priority (19)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/658,619 US8467842B2 (en) | 2010-02-10 | 2010-02-10 | Systems, devices, and methods including multi-harmonic optical detection of hemozoin nanoparticles |
| US12/658,617 US8840536B2 (en) | 2007-12-11 | 2010-02-10 | Systems, devices, and methods including paramagnetic oscillation, rotation and translation of hemozoin asymmetric nanoparticles in response to multi-harmonic optical detection of the presence of hemozoin |
| US12/658,638 | 2010-02-10 | ||
| US12/658,638 US8585567B2 (en) | 2007-12-11 | 2010-02-10 | Systems, devices, and methods including paramagnetic oscillation, rotation and translation of hemozoin asymmetric nanoparticles in response to multi-harmonic optical detection of the presence of hemozoin |
| US12/658,607 | 2010-02-10 | ||
| US12/658,589 US8388509B2 (en) | 2007-12-11 | 2010-02-10 | Systems, devices, and methods including paramagnetic oscillation, rotation, and translation of hemozoin asymmetric nanoparticles in response to dark-field or Rheinberg detection of the presence of hemozoin |
| US12/658,580 US8504129B2 (en) | 2007-12-11 | 2010-02-10 | Systems, devices, and methods including enhanced dark field detection of hemozoin nanoparticles |
| US12/658,617 | 2010-02-10 | ||
| US12/658,619 | 2010-02-10 | ||
| US12/658,589 | 2010-02-10 | ||
| US12/658,580 | 2010-02-10 | ||
| US12/658,607 US20100222774A1 (en) | 2007-12-11 | 2010-02-10 | Systems, devices, and methods for inducing ultraviolet energy generation via hemozoin nanoparticles in a biological tissue |
| US12/925,650 US8781184B2 (en) | 2010-02-10 | 2010-10-25 | Systems, devices, and methods for detection of malaria |
| US12/925,650 | 2010-10-25 | ||
| US12/925,653 | 2010-10-25 | ||
| US12/925,653 US9044141B2 (en) | 2010-02-10 | 2010-10-25 | Systems, devices, and methods including a dark-field reflected-illumination apparatus |
| US12/930,611 | 2011-01-10 | ||
| US12/930,611 US8774884B2 (en) | 2010-02-10 | 2011-01-10 | Systems, devices, and methods including a dark-field reflected-illumination apparatus |
| PCT/US2011/000259 WO2011100065A2 (en) | 2010-02-10 | 2011-02-10 | Systems, devices, and methods including a dark-field reflected-illumination apparatus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102753887A CN102753887A (en) | 2012-10-24 |
| CN102753887B true CN102753887B (en) | 2016-12-14 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102753096B (en) | Systems, devices, and methods including multi-harmonic optical detection of hemozoin nanoparticles | |
| US9524417B2 (en) | Systems, devices, and methods for detection of malaria | |
| US9044141B2 (en) | Systems, devices, and methods including a dark-field reflected-illumination apparatus | |
| Rumyantsev et al. | Fundamental bounds on the fidelity of sensory cortical coding | |
| Keiser | Biophotonics | |
| CN109788905A (en) | The optical imagery of diffusing media | |
| CN108474736A (en) | System and method for the imaging of light science of heredity | |
| Radbruch et al. | Intravital FRET: probing cellular and tissue function in vivo | |
| Sinha et al. | High-speed laser microsurgery of alert fruit flies for fluorescence imaging of neural activity | |
| Ruiz et al. | Smartphone fluorescence imager for quantitative dosimetry of protoporphyrin-IX-based photodynamic therapy in skin | |
| Hopp et al. | Subcellular mapping of dendritic activity in optic flow processing neurons | |
| Jain et al. | Backscattering polarimetric imaging of the human brain to determine the orientation and degree of alignment of nerve fiber bundles | |
| CN103167840B (en) | Comprise the system of details in a play not acted out on stage, but told through dialogues indirect illumination equipment, device and method | |
| JP6895297B2 (en) | Cell mass evaluation method and cell mass state analyzer | |
| CN102753887B (en) | Comprise the system of details in a play not acted out on stage, but told through dialogues indirect illumination equipment, device and method | |
| CN102753887A (en) | Systems, devices, and methods including a dark-field reflected-illumination apparatus | |
| Shin et al. | Recurrent pattern completion drives the neocortical representation of sensory inference | |
| Chon et al. | Digital phantoms generated by spectral and spatial light modulators | |
| WO2011100065A2 (en) | Systems, devices, and methods including a dark-field reflected-illumination apparatus | |
| EP2632380A1 (en) | Systems, devices, and methods including a dark-field reflected-illumination apparatus | |
| Lees et al. | Contribution of optical resolution to the spatial precision of two-photon optogenetic photostimulation in vivo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20161214 Termination date: 20180210 |