WO2005107939A1 - 圧電デバイスを用いた機器 - Google Patents
圧電デバイスを用いた機器 Download PDFInfo
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- WO2005107939A1 WO2005107939A1 PCT/JP2005/008487 JP2005008487W WO2005107939A1 WO 2005107939 A1 WO2005107939 A1 WO 2005107939A1 JP 2005008487 W JP2005008487 W JP 2005008487W WO 2005107939 A1 WO2005107939 A1 WO 2005107939A1
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- Prior art keywords
- piezoelectric
- flow path
- piezoelectric device
- outlet
- electrodes
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- 229910052751 metal Inorganic materials 0.000 claims abstract description 25
- 239000002184 metal Substances 0.000 claims abstract description 25
- 239000010409 thin film Substances 0.000 claims abstract description 25
- 239000000463 material Substances 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 92
- 210000000601 blood cell Anatomy 0.000 claims description 68
- 239000000523 sample Substances 0.000 claims description 59
- 238000000926 separation method Methods 0.000 claims description 37
- 239000000126 substance Substances 0.000 claims description 32
- 238000000105 evaporative light scattering detection Methods 0.000 claims description 30
- 230000005855 radiation Effects 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 17
- 230000008859 change Effects 0.000 claims description 16
- 238000001514 detection method Methods 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 10
- 239000008280 blood Substances 0.000 claims description 10
- 239000012530 fluid Substances 0.000 claims description 10
- 239000012488 sample solution Substances 0.000 claims description 10
- 239000011859 microparticle Substances 0.000 claims description 8
- 239000010419 fine particle Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 4
- 238000003018 immunoassay Methods 0.000 claims description 3
- 230000004308 accommodation Effects 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 238000012546 transfer Methods 0.000 claims description 2
- 238000004458 analytical method Methods 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 230000010355 oscillation Effects 0.000 abstract 1
- 238000010586 diagram Methods 0.000 description 25
- 210000003743 erythrocyte Anatomy 0.000 description 9
- 210000000265 leukocyte Anatomy 0.000 description 9
- 230000007423 decrease Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- -1 for example Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01D19/00—Degasification of liquids
- B01D19/0073—Degasification of liquids by a method not covered by groups B01D19/0005 - B01D19/0042
- B01D19/0084—Degasification of liquids by a method not covered by groups B01D19/0005 - B01D19/0042 using an electric current
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
- B01F31/87—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations transmitting the vibratory energy by means of a fluid, e.g. by means of air shock waves
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- B01F33/3031—Micromixers using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
Definitions
- the present invention relates to an apparatus using a piezoelectric device, and particularly to an apparatus suitable for processing, analyzing, and measuring biological components and the like.
- Japanese Patent Application Laid-Open No. 2001-188070 describes an automatic analyzer equipped with a stirring mechanism for stirring a sample and a reagent using a piezoelectric device.
- Japanese Patent Application Laid-Open No. 2001-242177 describes an automatic analyzer that generates ultrasonic waves by a piezoelectric device, generates a stirring swirling flow by acoustic radiation pressure by the ultrasonic waves, and thereby mixes and stirs a sample and a reagent.
- Japanese Patent Application Laid-Open No. 2001-255317 describes a measuring apparatus that generates ultrasonic waves by a piezoelectric device and oscillates the phosphorus-containing compound in sample water into phosphate ions by vibration with the ultrasonic waves. I have.
- Patent Document 1 Japanese Patent Application Laid-Open No. 2001-188070
- Patent Document 2 Japanese Patent Application Laid-Open No. 2001-242177
- Patent Document 3 JP 2001-255317 A
- the liquid can be agitated simply by generating ultrasonic waves using a piezoelectric device, but other complicated operations cannot be performed.
- An object of the present invention is to provide an apparatus capable of performing various and complicated operations or processes using a piezoelectric device.
- the device of the present invention includes a piezoelectric device having a piezoelectric element made of a piezoelectric material and a plurality of electrodes provided on both sides of the piezoelectric element and formed by a metal thin film pattern. Further, the piezoelectric element has a groove at a position outside the electrode.
- the piezoelectric device since the electrodes are formed by the metal thin film pattern, the piezoelectric device It can be provided at any position. Therefore, various devices using the piezoelectric device can be formed.
- vibrations, sound waves, surface waves, and the like are generated by generating vibrations of various frequencies in the piezoelectric element, and various operations using the vibrations are performed.
- a desired operation can be performed in the micro area
- FIG. 1A is a schematic diagram of a first example of a blood cell separation device according to the present invention
- FIG. 1B is a diagram showing a main part thereof.
- FIG. 2A is a diagram showing a main part of a second example of the blood cell separation device according to the present invention.
- FIG. 2B is a diagram showing a main part of a third example of the blood cell separation device according to the present invention.
- FIG. 3A is an exploded perspective view of a fourth example of the blood cell separation device according to the present invention
- FIG. 3B is a cross-sectional view thereof.
- FIG. 4A is a schematic diagram of a diaphragm of a first example of the mass detection device according to the present invention
- FIG. 4B is a cross-sectional view of the diaphragm
- FIG. FIG. 2 is a cross-sectional view of the example of FIG.
- FIG. 4D is a cross-sectional view of a modification of the first example of the mass detection device according to the present invention.
- FIG. 5 is an exploded perspective view of a second example of the mass detection device according to the present invention.
- FIG. 6A is a cross-sectional view of a main part of a second example of the mass detection device according to the present invention
- FIG. 6B is a cross-sectional view of the main part of a modification of the second example of the mass detection device according to the present invention.
- FIG. 7A and 7B are diagrams showing a cross-sectional configuration of a passage portion of a second example of the mass detection device according to the present invention.
- FIG. 8 is a diagram showing a relationship between frequency and time of vibration of an electrode of a piezoelectric device.
- FIG. 9 is a diagram for explaining a detection circuit for detecting the mass of a substance.
- FIG. 10A is a diagram showing a first example of a liquid sending device according to the present invention
- FIG. 10B is a diagram showing a second example of the liquid sending device according to the present invention
- FIG. 10C is a diagram showing a liquid sending device according to the present invention.
- FIG. 9 is a diagram illustrating a third example.
- FIG. 11A is a diagram schematically showing a sample analyzer according to the present invention
- FIG. 11B is a diagram showing a configuration of a separator unit
- FIG. 11C is a diagram showing a configuration of a sensor unit thereof
- FIG. 11D is a diagram thereof. It is a figure showing composition of a pump part.
- FIG. 12 is a diagram showing an overview of an immunoassay device according to the present invention.
- FIG. 13 is a view for explaining the structure and operation of a reaction container of the immunological analyzer according to the present invention.
- FIG. 14A is a diagram showing an overview of a microparticle membrane voltage measuring device according to the present invention
- FIGS. 14B, 14C, 14D, 14E, and 14F are diagrams for explaining the operation thereof.
- FIG. 15A is an exploded perspective view of a solution stirring device according to the present invention
- FIG. 15B is a cross-sectional view of a main part thereof.
- FIG. 16 is an explanatory diagram for explaining the operation of the solution stirring device according to the present invention.
- FIG. 17A is a cross-sectional view of a main part of a solution scattering device according to the present invention
- FIG. 17B is an explanatory diagram for explaining its operation.
- FIG. 18A is a diagram showing an overview of a bubble prevention device according to the present invention
- FIG. 18B is a diagram for explaining the operation thereof.
- FIG. 19A is a diagram showing an overview of a piezoelectric valve according to the present invention
- FIGS. 19B and 19C are diagrams for explaining the operation thereof.
- the blood cell separation apparatus of this example includes a substrate 100, a pair of piezoelectric devices 110 and 120, populations 181, 182, 183 and exits 191, 192, 193, and a population and exit. And a flow path to be connected.
- the channel has a central main channel 170, branches 174, 175, 176 on the inlet side and branches 171, 172, 173 on the outlet side.
- Branches 174, 175, and 176 of population Tsukuda J are connected to populations 181, 182, and 183, respectively, and branches 171, 172, and 173 of exit Tsukuda J are connected to exits 191, 192, and 193, respectively.
- the piezoelectric devices 110 and 120 are disposed on both sides of the central main channel 170.
- the flow path 170 and the branches 171, 172, 173, 174, 175, and 176 are formed in a tunnel shape inside the substrate 100, and the populations 181, 182, and 183 are provided on the upper surface of the substrate 100, and the outlets 191, 1 Reference numerals 92 and 193 are provided on the lower surface of the substrate 100.
- the piezoelectric devices 110 and 120 are provided so as to face each other on the inner wall of the main flow channel 170.
- FIG. 1B shows a main part of the blood cell separation device of the present example.
- the configuration and operation of the piezoelectric devices 110 and 120 will be described with reference to FIG. 1B.
- the two piezoelectric devices 110 and 120 have the same structure.
- the first piezoelectric device 110 includes a piezoelectric plate 111 and electrodes 112, 113, 114, and 115 formed on a surface of the piezoelectric plate 111 and formed of a metal thin film pattern.
- the second piezoelectric device 120 includes a piezoelectric plate 121 and electrodes 122, 123, 124, and 125 provided on the surface of the piezoelectric plate 121 and having a metal thin film pattern force.
- a vibration voltage is applied between the first and second electrodes 112 and 113 of the first piezoelectric device 110 and the fourth electrode 115, and the thickness of the piezoelectric plate 111 sandwiched therebetween is vibrated. Generates relatively weak sound waves.
- the piezoelectric plate 121 of the second piezoelectric device 120 receives a relatively weak sound wave from the first piezoelectric device 110, the first and second electrodes 122, 123 and the fourth electrode 125 Voltage is generated. By detecting this voltage, a sound wave can be detected.
- An oscillating voltage is applied between the third electrode 114 and the fourth electrode 115, and the thickness of the piezoelectric plate 111 interposed therebetween is oscillated to generate a relatively strong acoustic wave.
- An oscillating voltage is applied between the first and second electrodes 122 and 123 of the second piezoelectric device 120 and the fourth electrode 125, and the thickness of the piezoelectric plate 121 sandwiched therebetween is oscillated. Generates relatively weak sound waves.
- the piezoelectric plate 111 of the first piezoelectric device 110 receives a relatively weak sound wave from the second piezoelectric device 120, the first and second electrodes 112, 113 and the fourth electrode 115 Voltage is generated. By detecting this voltage, a sound wave can be detected.
- An oscillating voltage is applied between the third electrode 124 and the fourth electrode 125, and the thickness of the piezoelectric plate 121 interposed therebetween is oscillated to generate a relatively strong sound wave.
- the piezoelectric plate 111 is made of a piezoelectric material.
- the piezoelectric material for example, titanium titanate is known.
- blood cells are identified from the sample liquid (whole blood) by a blood cell separation device, and the blood cells are separated for each type.
- the sample liquid 132 is introduced from the central inlet 182, and the sheath liquids 131 and 133 are introduced from the inlets 181 and 183 on both sides.
- the three liquids are guided to the respective branches, and merge in the central main flow path 170.
- sample The liquid 132 and the sheath liquids 131 and 133 are controlled so as not to disturb the flow, that is, to form a laminar flow. Therefore, in the main channel 170, a laminar flow of three layers is formed without mixing the three liquids 131, 132, and 133.
- the three liquids are separated into three branches on the outlet side without mixing.
- the sample liquid 132 is guided to the central outlet 192 via the central branch 172, and is guided to the outlets 191 and 193 via the branch liquids 171 and 173 of the sheath liquids 131 and 133. .
- the piezoelectric device formed by the first and fourth electrodes 112 and 115 of the first piezoelectric device 110 and the piezoelectric plate 111 sandwiched therebetween is referred to as a first part, a first part.
- the piezoelectric device formed by the second and fourth electrodes 113 and 115 and the piezoelectric plate 111 interposed therebetween is connected to the second portion, the third and fourth electrodes 114 and 115, and the piezoelectric plate interposed therebetween.
- the piezoelectric device formed by 111 is the third part.
- a relatively weak sound wave 141 is generated by the first portions 112, 115, 111 of the first piezoelectric device 110. It is received by the corresponding first part 122, 125, 121 of the second piezoelectric device 120. Similarly, the second portion 113, 115, 111 of the first piezoelectric device 110 generates a relatively weak sound wave 142. It is received by the corresponding second part 123, 125, 121 of the second piezoelectric device 120.
- the first and second portions of the second piezoelectric device 120 can detect the presence of the blood cell 151 from the decrease in the intensity of the received sound wave.
- the amount of decrease in the intensity of the received sound wave is proportional to the size of the blood cell, that is, the cross-sectional area.
- the diameter of white blood cells is 10-15 m
- the diameter of red blood cells is 8 ⁇ m
- the diameter of platelets is 2-5 ⁇ m. Therefore, the amount of decrease in the received sound wave is the largest in the case of white blood cells, and the smallest in the case of platelets which are large for red blood cells. Therefore, the first and second portions of the second piezoelectric device 120 can identify the type of blood cell from the amount of decrease in the intensity of the received sound wave.
- leukocytes are detected by the first portions of the first and second piezoelectric devices 110 and 120.
- the third portion 114, 115, 111 of the first piezoelectric device 110 generates a relatively strong sound wave.
- the white blood cells 151 move in a direction approaching the second piezoelectric device 120 and are guided to the laminar flow of the sheath liquid 133 on the second piezoelectric device 120 side. Thereafter, the white blood cells 151 are guided to the outlet 193 via the branch 173 on the second piezoelectric device 120 side together with the sheath liquid 133. Leukocytes 151 can be collected from the sheath liquid from the third outlet 193.
- red blood cells are detected by first portions of the first and second piezoelectric devices 110 and 120.
- the red blood cells move in the direction approaching the first piezoelectric device 110 and are guided to the laminar flow of the sheath liquid 131 on the first piezoelectric device 110 side.
- the erythrocytes are thereafter guided together with the sheath liquid 131 to the outlet 191 via the branch 171 on the first piezoelectric device 110 side. Sheath fluid from the first outlet 191 can also collect red blood cells.
- FIG. 2A shows a main part of the blood cell separation device of this example.
- the blood cell separation device of this example has a flow channel and a pair of piezoelectric devices 210 and 220.
- the flow path has a central main flow path 270 and outlet branches 271 and 272.
- the flow path has two branches on the inlet side. It has an inlet connected to the two branches on the inlet side and an outlet connected to the branch on the outlet side.
- the piezoelectric devices 210 and 220 are arranged on both sides of the central main channel 270.
- the first piezoelectric device 210 has a piezoelectric plate 211 and electrodes 212, 213, and 214 provided on the surface of the piezoelectric plate 211 and having a metal thin film pattern force.
- the second piezoelectric device 220 has a piezoelectric plate 221 and electrodes 222 and 223 provided on the surface of the piezoelectric plate 221 and having a metal thin film pattern force.
- Sample liquid (whole blood) and sheath liquid are introduced from the two inlets, respectively.
- the sample liquid 231 and the sheath liquid 232 flow in a separated state as a laminar flow.
- a relatively weak sound wave 241 is generated by the first portions 212, 214, 211 of the first piezoelectric device 210.
- the second piezoelectric device 220 receives it and detects the passage of blood cells.
- a relatively strong sound wave 242 is generated by the second portions 213, 214, 211 of the first piezoelectric device 210.
- Blood cells are led to the sheath liquid 232 and to the outlet from the second branch 272.
- the sample liquid is led from the first branch 271 to the outlet.
- blood cells can be separated from the sample solution.
- FIG. 2B shows a main part of the blood cell separation device of the present example.
- the blood cell separation device of this example has a flow path and a piezoelectric device 230.
- the channel has a central main channel 270 and branches 271 and 272 on the outlet side.
- the flow path has two branches on the inlet side. It also has an inlet connected to the two branches on the inlet side and an outlet connected to the branch on the outlet side.
- the piezoelectric device 230 is arranged on one side of the central main channel 270.
- the piezoelectric device 230 has a piezoelectric plate 231 and electrodes 232 and 233 provided on the surface of the piezoelectric plate 231 and having a metal thin film pattern force.
- a sample liquid (whole blood) and a sheath liquid are introduced from each of the two inlet ports.
- the sample liquid 231 and the sheath liquid 232 flow in a separated state as a laminar flow.
- a relatively strong sound wave 243 is generated by the piezoelectric device 230.
- Blood cells are led to the sheath liquid 232 and to the outlet from the second branch 272.
- the sample liquid is led from the first branch 271 to the outlet.
- blood cells can be separated from the sample solution.
- the example shown in Fig. 2 is preferable when all blood cells are separated without discriminating the type of blood cells. Suitable. Therefore, it can be used as a serum separation filter. In this case, the serum at the outlet connected to the first branch 271 is also collected, and blood cells are obtained from the outlet connected to the second branch 272. Normal filter paper filter has clogging force The device of this example has the advantage of not causing clogging.
- the example shown in FIG. 2A is suitable when the blood cell concentration is relatively low, and the example shown in FIG. 2B is suitable when the blood cell concentration is relatively high!
- FIG. 3A is an exploded perspective view of the blood cell separation device of the present example
- FIG. 3B is a cross-sectional view after assembly.
- the blood cell separation device of the present example has an upper member 310 and a lower member 320, and a concave portion is formed on the inner surface of the upper member 310.
- This recess has a large depth! /, A portion 311A and a small depth, a portion 312A.
- the recess forms a closed space between the upper member 310 and the lower member 320.
- the closed space includes a storage portion 311 having a large depth and a passage portion 312 having a small depth.
- the upper member 310 has an inlet 313 and an outlet 314. The inlet 313 is connected to the housing 311, and the outlet 314 is connected to the passage 312.
- the lower member 320 is formed of a piezoelectric material, and electrodes 331 and 332 are provided on both surfaces thereof, which also have a metal thin film pattern force. In this way, a piezoelectric device is formed from the electrodes 331 and 332 and the piezoelectric plate sandwiched therebetween.
- a sample solution (whole blood) is introduced from the inlet 313.
- the sample liquid is accommodated in the accommodation section 311, and further, is guided from the passage section 312 to the outlet 314.
- An oscillating voltage is applied between the electrodes 331 and 332 to oscillate the thickness of the piezoelectric plate sandwiched therebetween, thereby generating a relatively strong sound wave. Due to the radiation pressure of the sound waves, the blood cells move away from the piezoelectric device and are stored in the storage unit 311.
- the sample liquid excluding the blood cells is led from the passage 312 to the outlet 314. From the outlet 314, a sample liquid from which blood cells have been removed is obtained.
- the mass detection device of this example has a disk-shaped diaphragm 400 formed of a piezoelectric material and electrodes 401 and 402 made of a metal thin film patterner mounted on both surfaces thereof.
- the electrodes 401 and 402 have circular holes 401A and 402A and lead portions 401B and 402B connected thereto.
- the leads 401B and 402B are connected to a circuit (not shown).
- the periphery of diaphragm 400 is supported by holder 410.
- the holder 410 has a concave portion, and a closed space 411 is formed by the concave portion and the vibration plate 400.
- the diaphragm 400 sandwiched therebetween vibrates.
- diaphragm 400 vibrates in the shearing direction. That is, the upper surface and the lower surface vibrate in opposite directions along the surface direction.
- the force using the diaphragm 400 in FIG. 4A is the same as the example shown in FIG. 4D.
- FIG. Is provided. By providing the grooves in this manner, the diaphragm easily vibrates.
- the electrode 401 on the surface of the vibration plate 400 is coated with a substance that binds to a specific substance called a linker.
- the diaphragm 400 is arranged so that the electrode 401 is immersed in the solution. For example, it may be mounted on the inner wall of the container in which it is stored.
- a specific substance in the solution is bonded to the linker applied to the surface of diaphragm 400.
- the natural frequency of diaphragm 400 changes. This change in the natural frequency is related to the mass of the substance bound to the linker.
- the mass of the substance bound to the linker can be measured. Assuming that the mass of the substance bound to the linker is proportional to the concentration of the substance contained in the solution, the concentration of the substance in the solution can be detected.
- FIG. 5 A second example of the mass detection device according to the present invention will be described with reference to FIG. 5, FIG. 6, and FIG.
- the mass detection device of this example has an upper member 510 and a lower member 520, and a concave portion 511A is formed on the inner surface of the upper member 510.
- the recess 511A forms a passage 511 (FIG. 6) which is a sealed space between the upper member 510 and the lower member 520.
- the upper member 510 has an inlet 513 and an outlet 514, and the inlet 513 and the outlet 5 are provided. 14 is connected to the passage 511.
- a recess 521 is formed in the lower member 520, and a circuit board 522 is disposed in the recess 521.
- the lower member 520 is formed of a piezoelectric material, and is provided with electrodes 525, 526 (only the electrode 525 is shown in FIG. 5) which also has a metal thin film pattern force on both surfaces thereof.
- a piezoelectric device is formed by the electrodes 525 and 526 and the piezoelectric plate sandwiched therebetween.
- the electrodes 525, 526 are located below and along the passage 511. Electrodes 525, 526, Q the electrodes 525, 526 having the inner surface electrode 526 to the electrode disposed 525 and the outer surface (the upper surface) (the lower surface) disposed (see FIG. 6) of the lower member 520, lead It is connected to the circuit of the circuit board 522 via the lines 527 and 528.
- FIG. 6 shows a cross-sectional configuration of the mass detection device of FIG.
- a groove 531 is formed on the inner surface (upper surface) of the lower member 520 so as to surround the periphery of the electrode 525.
- a groove 532 is formed on the inner surface (upper surface) of the lower member 520 so as to surround three sides of the electrode 525.
- electrode 525 includes two electrodes 525 °, 525 °. The reason for providing the two electrodes 525 ° and 525 ° will be described later with reference to FIG.
- FIG. 7 shows a cross-sectional configuration of the passage portion 511 of the mass detection device shown in FIGS.
- a substance called a linker 541, 542 that binds to a specific substance is arranged on the surface of the electrode 525.
- the electrodes 525, 526 oscillate in the shear direction, as shown in FIG. That is, the upper surface and the lower surface vibrate along the surface direction and in directions opposite to each other.
- the linkers 541, 542 vibrate and bind to a particular substance.
- FIG. 8 a method for measuring the amount of a substance bound to linkers 541 and 542 will be described.
- Each curve in FIG. 8 shows the relationship between frequency and time of vibration of the electrodes of the piezoelectric device.
- the frequency decreases with time, as shown in Figure 8 ⁇ . This is because the weight of the vibrating part increases because the substance is bonded to the linker.
- noise or drift occurs due to various factors. Therefore, as shown in FIG. 8B, noise or drift is superimposed on the frequency fluctuation curve. Therefore, as shown in FIG. 6, two electrodes 525A and 525B are provided for each electrode. One electrode is not provided with a linker, and the other electrode is provided with a linker. As shown in FIG.
- a curve 601 indicating a change in the vibration frequency of the electrode without the linker and a curve 602 indicating the change in the vibration frequency of the electrode with the linker are obtained.
- Curve 601 represents noise or drift. Accordingly, by subtracting the curve 601 from the curve 602, a curve 603 from which noise and drift have been removed is obtained as shown in FIG. 8D. Using this curve 603, the amount of substance bound to the linker can be accurately detected.
- curve 604 shows the change in frequency at an electrode with a linker that binds a first substance
- curve 605 shows the change in frequency at an electrode with a linker that binds a second substance.
- the detection circuit shown in FIG. 9A has electrodes 701A and 701B, a switch 702, a DC power supply 703, a transistor 704, and impedances 705, 706, and 707 mounted on both sides of the piezoelectric plate.
- a resonant circuit force S is formed by the transistor 704 and the impedances 705, 706, 707.
- the switch 702 When the switch 702 is turned on, the voltage from the DC power supply 703 is applied to the electrodes 701A, 701B via the resonance circuits 704, 705, 706, 707.
- the resonance frequency that is, the natural frequency is measured by a frequency counter (not shown).
- the resonance frequency is a function of the mass of the substance bound to the electrode linker. Therefore, the mass of the substance can be measured from the resonance frequency.
- the detection circuit of this example has electrodes 711 A and 711 B, switches 712 and 713, a DC power supply 714, and a resistor 715 mounted on both sides of the piezoelectric plate.
- the switch connected to the DC power supply 714 Switch 712 is turned on, and switch 713 connected to resistor 715 is turned off.
- charges are accumulated between the electrodes 711A and 711B, and a potential V is generated.
- FIG. 9B charges are accumulated between the electrodes 711A and 711B, and a potential V is generated.
- the switch 712 connected to the DC power supply 714 is turned off, and the switch 713 connected to the resistor 715 is turned on.
- the potential V between the electrodes 711A and 71IB oscillates.
- the resonance frequency can be obtained by detecting the frequency of this vibration. From the resonance frequency obtained in this way, the mass of the substance can be measured.
- the first example of the liquid sending device shown in FIG. 10A has an upper member 810 and a lower member 820, and the upper member 810 has a concave portion 811 on the inner surface.
- the recess 811 forms a sealed space 830 between the side member 810 and the lower member 820.
- the side member 810 is provided with an inlet 815 and an outlet 816, and the inlet 815 and the outlet 816 are connected to the closed space 830.
- the concave portion 811 on the inner surface of the upper member 810 has an inclined portion 811A and a flat portion 811B.
- an inclined portion 830A and a passage portion 830B are formed in the closed space 830.
- the lower member 820 is formed of a piezoelectric material, and has electrodes 821 and 822 formed of a metal thin film pattern on both surfaces thereof.
- a piezoelectric device is formed by the electrodes 821 and 822 and the piezoelectric plate sandwiched therebetween.
- the electrodes 821 and 822 are arranged at positions corresponding to the inclined portions 830A.
- the solution is introduced into the closed space 830 from the inlet 815.
- an oscillating voltage is applied to the electrodes 821 and 822
- the portion of the piezoelectric material sandwiched between the electrodes 821 and 822 vibrates to generate sound waves.
- the sound wave reflects off the inclined portion 811A of the concave portion 811 on the inner surface of the upper member 810 as shown by the arrow A, and is guided toward the outlet 816.
- the solution contained in the sealed space 830 is guided toward the outlet 816 as indicated by the arrow B by the radiation pressure of this sound wave.
- the second example of the liquid transfer device shown in FIG. 10B differs from the first example of FIG. 10A in that the concave portion 811 on the inner surface of the upper member 810 does not have the inclined portion 811A, that is, It has only a flat part. Accordingly, a passage portion 830 having a constant height is formed in the closed space 830.
- the lower member 820 is formed of a piezoelectric material, and has electrodes 821 and 822 formed of a metal thin film pattern on both surfaces thereof.
- the electrodes 821 and 822 and the piezoelectric plate sandwiched between them thus, a piezoelectric device is formed.
- the electrodes 821 and 822 are arranged along the closed space 830.
- the solution is introduced into the closed space 830 from the inlet 815.
- an oscillating voltage to the electrodes 821 and 822 at a frequency different from that in the example of Fig. 10A, the thickness of the piezoelectric material sandwiched between the electrodes 821 and 822 vibrates, and a surface wave is generated on the surface Is done.
- the electrode 821 may be composed of a plurality of electrodes, and these electrodes may be sequentially applied with an oscillating voltage in a direction from the entrance 815 to the exit 816 to generate a surface wave.
- the third example of the liquid sending device shown in Fig. 10C is different from the second example of Fig. 10B in that no piezoelectric device is provided. In this example, no sound wave generated by the piezoelectric device is used. Instead, use capillary action.
- the solution is introduced into the closed space 830 from the inlet 815. The solution moves in the closed space 830 in the direction of the outlet by capillary action, as indicated by arrow D.
- the sample analyzer of this example has an upper member 910 and a lower member 920, and a circuit board 913 is disposed between the upper member 910 and the lower member 920.
- a groove 930 is provided on the upper surface of the lower member 920, that is, on the inner surface.
- the groove 930 forms a sealed space between the upper member 910 and the lower member 920.
- an inlet 911 and an outlet 912 are provided in the upper member 910.
- One end of groove 930 is connected to inlet 911 and the other end of groove 930 is connected to outlet 912.
- Groove 930 has first, second, and third portions.
- the first portion of the groove 930 forms a sealed space separator portion 931 as shown in FIG. 11B
- the second portion of the groove 930 forms a sensor portion of the sealed space as shown in FIG. 11C.
- 932 is formed
- the third part of the groove 930 forms a pump part 933 of the enclosed space as shown in FIG. 11D.
- electrodes 921 and 922 which are also metal thin film patterns are provided on both surfaces of the lower member 920.
- the lower member 920 is formed from a piezoelectric material.
- a piezoelectric device is formed by the electrodes 921 and 922 and the piezoelectric plate sandwiched therebetween.
- the operation of the separator section 931 of this example is the same as the operation of the fourth example of the blood cell separation device described with reference to FIG.
- electrodes 921 and 922 made of a metal thin film pattern are provided on both surfaces of the lower member 920.
- the lower member 920 is formed from a piezoelectric material.
- a piezoelectric device is formed by the electrodes 921 and 922 and the piezoelectric plate sandwiched therebetween. Further, a groove 923 is provided around the electrode.
- the operation of the sensor unit 932 of this example is the same as the operation of the example of the mass detection device described with reference to FIG.
- electrodes 921 and 922 made of a metal thin film pattern are provided on both surfaces of the lower member 920.
- the lower member 920 is formed from a piezoelectric material.
- a piezoelectric device is formed by the electrodes 921 and 922 and the piezoelectric plate sandwiched therebetween.
- the operation of the pump unit 933 of the present example is the same as the operation of the example of the liquid sending device described with reference to FIG. 10A, and the details are omitted.
- the immunological analyzer has a circular holder plate 1201, and a number of reaction vessels 1202 are held in one holder plate 1201.
- the reaction vessel 1202 is maintained at a predetermined temperature by a thermostat 1203.
- the reaction vessel of the present example has a vessel section 1309 having a rectangular or rectangular cross section, and a piezoelectric device provided on the wall of the vessel section.
- the container 1309 contains a liquid 1310 which is a mixture of an ampoule and a reagent necessary for an immune reaction.
- the sample solution contains a plurality of types of antibody components to be measured. As shown in the figure, the antibody components are schematically indicated by circles, the shading of the circles indicates the type of the antibody component, and the number of circles indicates the concentration.
- the piezoelectric device has a piezoelectric plate 1301, upper stirring electrodes 1302, 1303, and lower mass detection electrodes 1304, 1305, 1306, 1307, 1308, 1309. These electrodes are formed of a metal thin film pattern, and are provided on both sides of the side wall of the container, that is, on the inner wall and the outer wall, respectively, as shown in the figure.
- the stirring electrode is arranged at a position near the liquid surface 1311, and the mass detection electrode is arranged at a position below the liquid surface 1311.
- a linker 1305A, 1307A, 1309A is mounted on the surface of the mass detection electrodes 1305, 1307, 1309 mounted on the inner wall side of the solution.
- the three electrodes are equipped with linkers that bind to different antibody components.
- the piezoelectric plate 1301 sandwiched between the electrodes vibrates in the shear direction. . That is, the inner surface of the piezoelectric plate 1301 vibrates along the surface direction.
- the antibody component substance binds to the linker.
- the natural frequency of the piezoelectric plate vibrated by the mass detection electrode changes.
- the change in the natural frequency is a function of the mass of the antibody component bound to the linker.
- the mass of the antibody component bound to the linker indicates the concentration of the antibody component. Therefore, by measuring the amount of change in the natural frequency, the concentration of the antibody component is detected.
- the liquid 1310 in the container is replaced with the cleaning liquid 1312, and an oscillating voltage is again applied between the stirring electrodes 1302 and 1303.
- the cleaning liquid is agitated, and impurities adhering to the linker are cleaned. After cleaning the impurities in this way, measure the change in the natural frequency of the piezoelectric plate.
- the microparticle membrane voltage measuring device of this example has an upper part 1410 and a lower part 1420, and a concave part 1411A is formed on the inner surface of the upper member 1410.
- the recess 1411A forms a passage 1411 that is a sealed space between the upper member 1410 and the lower member 1420.
- the upper member 1410 is provided with an inlet 1413 and an outlet 1414, and the inlet 1413 and the outlet 1414 are connected to a passage portion 1411.
- a concave portion 1421 is formed in the lower member 1420, and a needle 1422 is arranged in the concave portion 1421.
- the upper member 1410 is formed of a piezoelectric material, and electrodes 1415 and 1416 are provided on both surfaces thereof.
- a piezoelectric device is formed by the electrodes 1415 and 1416 and the piezoelectric plate sandwiched therebetween.
- the lower member 1420 is formed of a piezoelectric material, and has electrodes 1425 and 1426 formed of a metal thin film pattern on both surfaces thereof. Piezoelectric device is formed by electrodes 1425, 1426 and piezoelectric plate sandwiched between them . These piezoelectric devices are arranged at positions corresponding to the concave portions 1421.
- the solution is introduced into the passage 1411 through the inlet 1413.
- the solution passes through passage 1411 and exits through outlet 1414.
- the fine particles 1430 are introduced from the inlet 1413 into the passage 1411.
- the microparticles 1430 move in the passage due to the flow of the solution and reach the concave portions 1421.
- an oscillating voltage is applied to the electrodes 1415 and 1416 constituting the upper piezoelectric device to generate sound waves. Due to the radiation pressure of the sound waves, the microparticles 1430 move and come into contact with the needle 1422 in the recess 1421. Measure the voltage between needle 1422 and the solution.
- the application of the voltage to the electrodes 1415 and 1416 constituting the upper piezoelectric device is stopped.
- An oscillating voltage is applied to the electrodes 1425 and 1426 constituting the lower piezoelectric device to generate sound waves.
- the microparticles 1430 are ejected from the concave portions 1421 by the radiation pressure of the sound waves.
- the microparticles 1430 are discharged to the outlet by the solution flowing in the passage 1411.
- the solution stirring device has an upper member 1510, a sample plate 1520, and a lower member 1530.
- a plurality of sample storage sections 1521 are formed on the upper surface of the sample plate, and the sample storage section 1521 stores a sample liquid 1522.
- the sample container 1521 may be a concave portion formed on the upper surface of the sample plate 120.
- the sample receiving section 1521 may be cylindrical or other shape.
- the lower member 1530 is formed of a piezoelectric material, and electrodes 1531 and 1532 are provided on both surfaces thereof, which also have a metal thin film pattern force.
- the electrodes 1531 and 1532 and the piezoelectric plate sandwiched therebetween form a piezoelectric device.
- a vibration voltage is applied between the electrodes 1531 and 1532, the piezoelectric plate sandwiched between the electrodes 1531 and 1532 vibrates. This vibration is transmitted to the sample liquid 1522 stored in the sample storage section 1521, and the sample liquid 1522 is stirred.
- the lower member 1530 is relatively movable with respect to the sample plate 1520, and can be arranged at any position.
- the electrodes 1531 and 1532 are arranged below the center of the sample container 1521. Continuous application of oscillating voltage to electrodes 1531 and 1532 To generate relatively large sound waves. Due to the radiation pressure of the sound wave, the liquid surface of the sample liquid 1522 rises along the central axis of the sample storage section 1521 and collides with the upper member 1510. The colliding sample liquid 1522 falls along the inner wall. As a result, the sample liquid 1522 circulates through the sample container 1521 and is stirred, as indicated by the arrow in the drawing. In the example shown in FIG.
- the electrodes 1531 and 1532 are arranged below the position away from the center of the sample storage unit 1521. Therefore, the sample liquid 1522 rises along the inner wall of the sample storage portion 1521 and collides with the upper member 1510 by the sound wave generated by applying the oscillating voltage to the electrodes 1531 and 1532. The colliding sample liquid 1522 falls along the opposite inner wall. As a result, the sample liquid 1522 circulates through the sample container 1521 and is stirred, as indicated by the arrow in the drawing.
- electrodes 1531 and 1532 are arranged below the center of sample storage section 1521.
- An oscillating voltage is intermittently applied to the electrodes 1531 and 1532 to generate relatively small sound waves intermittently.
- the liquid level of the sample liquid 1522 rises along the central axis of the sample storage section 1521 and flows around. As a result, the sample liquid 1522 circulates through the sample container 1521 and is stirred, as indicated by the arrow in the drawing.
- the solution scattering device has a piezoelectric plate 1720.
- the piezoelectric plate 1720 is formed of a piezoelectric material, and has electrodes 1721 and 1722 formed of a metal thin film pattern on both surfaces thereof.
- the electrodes 1721, 1722 and the piezoelectric plate sandwiched therebetween form a piezoelectric device.
- An object on which the solution is scattered by the solution scattering device of the present example is a member 1710 having a plurality of recesses 1711 on the upper surface. Unnecessary liquid 1712 remains in recess 1711.
- the unnecessary liquid 1712 includes a cleaning liquid, an etching liquid, and the like.
- the bubble prevention device has an upper member 1810 and a lower member 1820.
- a groove is formed on the inner surface of the upper member 1810, that is, on the lower surface. This groove allows the upper member 1810 and the lower A passage 1811 which is a closed space is formed between the members 1820.
- the upper member 1810 has an inlet 1815 and an outlet 1816. These inlet 1815 and outlet 1816 are connected to passage 1811.
- the passage 1811 includes narrow passages 1811A and 1811B at both ends and a thick passage 1811C between them.
- the lower member 1820 also has a piezoelectric material force, and electrodes 1821 and 1822 made of a metal thin film pattern are provided on both surfaces thereof.
- a piezoelectric device is formed by the electrodes 1821 and 1822 and the piezoelectric plate sandwiched therebetween. Liquid is introduced through inlet 1815. Liquid 1830 is directed to outlet 1816 via passage 1811. When the inside diameter of the passage suddenly increases, bubbles 1831 are easily generated there. For example, air bubbles are generated in a thick passage 1811C. These bubbles often adhere to the inner wall and do not disappear. In this example, the vibration is generated by the piezoelectric device. This vibration is transmitted to the inner wall where the air bubbles adhere, and the air bubbles move away from the inner wall and into the liquid. Thus, the generation of bubbles is prevented.
- the piezoelectric valve has an upper member 1910 and a lower member 1920.
- a groove 1911 is formed on the inner surface of the upper member 1910, that is, on the lower surface.
- the groove 1911 forms a closed space between the upper member 1910 and the lower member 1920.
- the lower member 1920 has two inlets 1915A, 1915B and an outlet 1916. Inlets 1915A and 1915B are connected to both ends of the passage.
- the upper member 1910 is made of a piezoelectric material, and is provided with electrodes 1931 and 1932 formed of a metal thin film pattern so as to sandwich the piezoelectric member.
- a piezoelectric device is formed by the electrodes 1931 and 1932 and the piezoelectric plate sandwiched therebetween.
- the piezoelectric device is provided along the groove 1911 as shown, and has a function of blocking the flow of the liquid along the passage.
- FIG. 19B shows the structure of the passage. As shown, this passage has a curved path in which a thin plate member 1912 is located. This plate member 1912 is elastically deformable. By applying an oscillating voltage between these two electrodes 1931 and 1932, a sound wave is generated. The radiation pressure of this sound wave is transmitted to the plate member 1912. As shown in FIG. 19C, the plate-shaped member 1912 is elastically deformed by the radiation pressure of the sound wave, and closes the passage. Thereby, the flow of the fluid through the passage is blocked. When the voltage between the two electrodes is released, The generation of the sound wave is stopped, and the plate member returns to the original position. Thereby, the flow of the fluid through the passage is resumed.
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Abstract
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JP2010538253A (ja) * | 2007-08-31 | 2010-12-09 | ビバクタ、リミテッド | センサ |
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US9217144B2 (en) | 2010-01-07 | 2015-12-22 | Gen9, Inc. | Assembly of high fidelity polynucleotides |
US9216414B2 (en) | 2009-11-25 | 2015-12-22 | Gen9, Inc. | Microfluidic devices and methods for gene synthesis |
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