CN117497588A - Biological sensing chip, preparation method thereof and analysis device - Google Patents
Biological sensing chip, preparation method thereof and analysis device Download PDFInfo
- Publication number
- CN117497588A CN117497588A CN202210886197.8A CN202210886197A CN117497588A CN 117497588 A CN117497588 A CN 117497588A CN 202210886197 A CN202210886197 A CN 202210886197A CN 117497588 A CN117497588 A CN 117497588A
- Authority
- CN
- China
- Prior art keywords
- layer
- substrate
- semiconductor film
- channel region
- sensing
- 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.)
- Pending
Links
- 238000004458 analytical method Methods 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 239000010410 layer Substances 0.000 claims abstract description 223
- 239000004065 semiconductor Substances 0.000 claims abstract description 72
- 239000000758 substrate Substances 0.000 claims abstract description 66
- 239000000523 sample Substances 0.000 claims abstract description 62
- 239000011241 protective layer Substances 0.000 claims abstract description 41
- 230000004048 modification Effects 0.000 claims abstract description 20
- 238000012986 modification Methods 0.000 claims abstract description 20
- 230000000149 penetrating effect Effects 0.000 claims abstract description 5
- 239000010408 film Substances 0.000 claims description 60
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 37
- 229910021389 graphene Inorganic materials 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 26
- 239000000463 material Substances 0.000 claims description 22
- 230000005669 field effect Effects 0.000 claims description 17
- 229910052710 silicon Inorganic materials 0.000 claims description 15
- 239000010703 silicon Substances 0.000 claims description 15
- 238000002955 isolation Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000010931 gold Substances 0.000 claims description 6
- 239000007769 metal material Substances 0.000 claims description 6
- 229910018072 Al 2 O 3 Inorganic materials 0.000 claims description 5
- 229910052737 gold Inorganic materials 0.000 claims description 5
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 4
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 3
- 229910052732 germanium Inorganic materials 0.000 claims description 3
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 claims description 3
- CWQXQMHSOZUFJS-UHFFFAOYSA-N molybdenum disulfide Chemical compound S=[Mo]=S CWQXQMHSOZUFJS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052982 molybdenum disulfide Inorganic materials 0.000 claims description 3
- ITRNXVSDJBHYNJ-UHFFFAOYSA-N tungsten disulfide Chemical compound S=[W]=S ITRNXVSDJBHYNJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 2
- 239000010409 thin film Substances 0.000 claims description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 239000012491 analyte Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 36
- 238000001514 detection method Methods 0.000 description 34
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 14
- 230000008569 process Effects 0.000 description 13
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 230000008859 change Effects 0.000 description 9
- 238000010586 diagram Methods 0.000 description 8
- 229910052751 metal Inorganic materials 0.000 description 8
- 239000002184 metal Substances 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 238000001179 sorption measurement Methods 0.000 description 8
- 239000012535 impurity Substances 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000005530 etching Methods 0.000 description 6
- 229920002120 photoresistant polymer Polymers 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 5
- 238000005229 chemical vapour deposition Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000000059 patterning Methods 0.000 description 5
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 5
- 239000004926 polymethyl methacrylate Substances 0.000 description 5
- 229910052814 silicon oxide Inorganic materials 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 238000001259 photo etching Methods 0.000 description 3
- 238000001020 plasma etching Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 2
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000011889 copper foil Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002853 nucleic acid probe Substances 0.000 description 2
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 238000004544 sputter deposition Methods 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910010413 TiO 2 Inorganic materials 0.000 description 1
- -1 acryl Chemical group 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000003793 prenatal diagnosis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Chemical compound [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001039 wet etching Methods 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L29/00—Semiconductor devices adapted for rectifying, amplifying, oscillating or switching, or capacitors or resistors with at least one potential-jump barrier or surface barrier, e.g. PN junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
- H01L29/66—Types of semiconductor device ; Multistep manufacturing processes therefor
- H01L29/68—Types of semiconductor device ; Multistep manufacturing processes therefor controllable by only the electric current supplied, or only the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched
- H01L29/76—Unipolar devices, e.g. field effect transistors
- H01L29/772—Field effect transistors
- H01L29/78—Field effect transistors with field effect produced by an insulated gate
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L29/00—Semiconductor devices adapted for rectifying, amplifying, oscillating or switching, or capacitors or resistors with at least one potential-jump barrier or surface barrier, e.g. PN junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
- H01L29/66—Types of semiconductor device ; Multistep manufacturing processes therefor
- H01L29/66007—Multistep manufacturing processes
- H01L29/66015—Multistep manufacturing processes of devices having a semiconductor body comprising semiconducting carbon, e.g. diamond, diamond-like carbon, graphene
- H01L29/66037—Multistep manufacturing processes of devices having a semiconductor body comprising semiconducting carbon, e.g. diamond, diamond-like carbon, graphene the devices being controllable only by the electric current supplied or the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched, e.g. three-terminal devices
- H01L29/66045—Field-effect transistors
Abstract
The invention discloses a biological sensing chip, a preparation method thereof and an analysis device, wherein the biological sensing chip comprises: the semiconductor device comprises a substrate, a semiconductor film layer, a source electrode layer, a drain electrode layer, a gate electrode layer, a protective layer, a sensing layer and a probe modification layer arranged on the sensing layer. The protective layer covers the surface of the semiconductor film layer of the channel region, and the orthographic projection of the channel region on the substrate is positioned in the orthographic projection of the protective layer on the substrate; the probe modification layer comprises a probe and is used for identifying an object to be detected in the solution to be detected; the sensing layer has a conductive portion penetrating the protective layer and contacting the semiconductor film of the channel region, so that charges generated by the combination of the probe and the analyte are transferred to the semiconductor film through the conductive portion.
Description
Technical Field
The invention relates to the technical field of molecular biology, in particular to a biological sensing chip, a preparation method thereof and an analysis device.
Background
Compared with an optical/magnetic detection analysis method based on marking molecules, the semiconductor-based unmarked nanoelectronic biochemical sensing technology has better performance in convenience and real-time. Taking a graphene field effect transistor biochemical sensor as an example, the graphene field effect transistor biochemical sensor belongs to an ion sensitive field effect transistor, and sensing is performed by detecting conductivity change of a graphene channel due to field effect when ions or biochemical molecules are combined. Graphene field effect biochemical sensors are receiving widespread attention due to their extremely high carrier mobility and low electrical noise. Recent researches on graphene biochemical sensors enable accurate monitoring of biomarkers of a human body and chemical substances in the environment at extremely low concentration, and have extremely great application potential in early diagnosis and environmental assessment.
Therefore, how to improve the accuracy of the detection result of a biosensor such as a graphene field effect transistor biochemical sensor is a major issue of long-term attention of many researchers.
Disclosure of Invention
The present invention has been made in view of the above problems, and has as its object to provide a biosensor chip, a method of manufacturing the same, and an analysis device which overcome or at least partially solve the above problems.
In a first aspect, embodiments of the present disclosure provide a biosensor chip, including:
a substrate;
a semiconductor film layer located on the substrate;
the source electrode layer and the drain electrode layer are respectively positioned at two ends of the semiconductor film layer, and a channel region is defined on the semiconductor film layer;
the protective layer covers the surface of the semiconductor film layer of the channel region, and the orthographic projection of the channel region on the substrate is positioned in the orthographic projection of the protective layer on the substrate;
a sensing layer and a probe modification layer disposed on the sensing layer, the probe modification layer including a probe for identifying an object to be measured in a solution to be measured, the sensing layer having a conductive portion passing through the protective layer and contacting the semiconductor film of the channel region such that charges generated by the probe in combination with the object to be measured are transferred to the semiconductor film through the conductive portion;
and the gate layer is positioned between the source electrode layer and the drain electrode layer and forms a field effect transistor with the source electrode layer, the drain electrode layer and the channel region.
Further, the above-mentioned biosensing chip further includes: the micro-fluid flow channel is respectively communicated with the solution chamber to be detected, the sample inlet and the sample outlet, and the orthographic projection of the solution chamber to be detected on the substrate is positioned in the orthographic projection of the sensing layer on the substrate.
Further, an isolation layer is arranged between the sensing layer and the probe modification layer, and the conductivity of the isolation layer is lower than that of the sensing layer.
Further, the material of the isolation layer is oxide, and the oxide layer is: tiO (titanium dioxide) 2 、Al 2 O 3 、SiO 2 Or Si (or) 3 NO 4 。
Further, the sensing layer is made of a metal material, and the metal material is aluminum or gold.
Further, an orthographic projection of the sensing layer on the substrate is located within an orthographic projection of the channel region on the substrate.
Further, the extending direction of the conductive part to the surface of the semiconductor film layer is perpendicular to the substrate.
Further, the substrate is provided with a plurality of field effect transistors, the plurality of field effect transistors share a source electrode layer, a drain electrode layer and electrode ends corresponding to a grid electrode layer, and the sensing layers corresponding to the different field effect transistors are arranged at intervals.
Further, the width of the channel region: length greater than or equal to 1:2, the length of the channel region is greater than or equal to 10 microns, wherein the length is the spacing between the source layer and the drain layer.
Further, the material of the semiconductor film layer may be any one of the following materials:
graphene, molybdenum disulfide, tungsten disulfide, and organic semiconductor thin films containing silicon or germanium.
Further, the gate layer comprises a back gate and a top gate, the top gate is arranged on the protective layer, and the back gate is arranged on the surface of the substrate.
In a second aspect, embodiments of the present disclosure further provide a method for manufacturing a biosensor chip, where the method includes:
forming a semiconductor film layer on a substrate;
forming a source electrode layer and a drain electrode layer to define a channel region on the semiconductor film layer;
forming a protective layer on the channel region, wherein the orthographic projection of the channel region on the substrate is positioned in the orthographic projection of the protective layer on the substrate;
forming a sensing layer on the protective layer, and modifying a probe on the surface of the sensing layer, wherein the sensing layer is provided with a conducting part penetrating through the protective layer and contacting with a semiconductor film layer of the channel region, so that charges generated by combining the probe and an object to be detected in a solution to be detected are transferred to the semiconductor film layer through the conducting part;
a gate layer is formed between the source and drain layers.
In a third aspect, an embodiment of the present application provides an analysis device, including the biosensing chip described in the first aspect.
The technical scheme provided by the embodiment of the specification has at least the following technical effects or advantages:
according to the biological sensing chip provided by the embodiment of the specification, the channel region of the semiconductor film layer is covered with the protective layer, so that the semiconductor film layer serving as the sensitive layer is prevented from being in direct contact with a solution to be detected in the detection process, and on the basis, the sensing layer is additionally arranged, and the detection modification layer is arranged on the sensing layer. Therefore, the change of the charge signal of the object to be detected can be sensed, and the interference of nonspecific adsorption of impurities in the solution to be detected to the detection result can be reduced, so that the noise of the detection signal can be reduced, and the accuracy and stability of the detection result can be improved.
The foregoing description is only an overview of the present invention, and is intended to be implemented in accordance with the teachings of the present invention in order that the same may be more clearly understood and to make the same and other objects, features and advantages of the present invention more readily apparent.
Drawings
Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the application. Also, like reference numerals are used to designate like parts throughout the figures. In the drawings:
fig. 1 is a schematic structural diagram of a biosensor chip according to an embodiment of the present disclosure;
FIG. 2 is a schematic diagram of a channel region of a biosensor chip according to an embodiment of the present disclosure;
FIG. 3 is a schematic diagram showing the power-up of a biosensor chip according to an embodiment of the present disclosure;
fig. 4 is a schematic structural diagram of a second embodiment of the disclosure;
fig. 5 is a schematic structural diagram III of a biosensor chip according to an embodiment of the present disclosure;
FIG. 6 is a schematic diagram of a biosensor chip according to an embodiment of the present disclosure;
fig. 7 is a schematic diagram of a structure of a biosensor chip according to an embodiment of the present disclosure;
FIG. 8 is a flowchart of a method for manufacturing a biosensor chip according to an embodiment of the present disclosure;
FIG. 9 is a schematic diagram of a cover plate of a biosensing chip according to an embodiment of the present disclosure;
FIG. 10 is a cross-sectional view AA in FIG. 9;
fig. 11 is a sectional view of BB in fig. 9.
Detailed Description
However, the semiconductor field effect transistor biosensor based on charge detection has some challenges to be solved in practical application, and besides the influence of the common debye shielding effect, the inventor finds that the complexity of the biochemical detection environment makes the background ions possibly adsorbed on the surface of the sensor, so as to interfere with the electrical performance of the sensor.
Taking a graphene Field effect transistor (Field-effect Transistors, FET) biosensor as an example, a common design structure of the graphene FET biosensor has two structures, namely a back gate structure and a liquid gate structure, and the common characteristic is that a solution to be measured is in direct contact with graphene. In practical applications, the to-be-detected object such as target molecules often exist in a complex solution system, and direct contact between the to-be-detected solution and the graphene surface is difficult to avoid in the specific recognition process, so that nonspecific adsorption of other ions and impurities in the solution on the graphene surface is caused. Graphene is a two-dimensional material with extremely sensitive induction, and the adsorption can bring large background noise to an electrical detection result, so that the accuracy and sensitivity of the detection result are affected.
Based on the above, the inventor proposes a biological sensing chip, by covering a protective layer on a channel region of a semiconductor film layer, the semiconductor film layer is prevented from being in direct contact with a solution to be detected in a detection process, and on the basis, a sensing layer is additionally arranged, and a detection modification layer is arranged on the sensing layer. Therefore, the method can induce the change of the charge signal of the object to be detected, and reduce the interference of nonspecific adsorption of impurities in the solution to be detected to the detection result, thereby being beneficial to reducing the noise of the detection signal, improving the accuracy and stability of the detection result and improving the problem of interference of the complexity of the solution to the performance of the semiconductor material such as graphene in the detection process.
Exemplary embodiments of a bio-sensing chip, a method of manufacturing the same, and an analysis device provided by the present disclosure will be described in detail below with reference to the accompanying drawings. It is noted that in the drawings, the size of layers and regions may be exaggerated for clarity of illustration. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. The term "plurality" as used herein includes two or more than two cases.
In a first aspect, embodiments of the present disclosure provide a bio-sensor chip, as shown in fig. 1, including: a substrate 100 and FET sensing cells disposed on the substrate 100. The FET sensing unit includes: semiconductor film 102, source layer 104, drain layer 106, gate layer, protective layer 108, sensing layer 110, and probe modification layer 112.
The substrate 100 may be a glass-based or silicon-based adaptive base material. The glass-based substrate is beneficial to improving the light transmission performance of the biological sensing chip. The silicon substrate may be an undoped silicon wafer, or may be an n/p type doped silicon substrate.
The semiconductor film 102 is located on the substrate 100, and is a sensitive layer of the bio-sensor chip, and can sense the change of the charge signal of the object to be measured. For example, the material of the semiconductor film layer 102 may be graphene. Alternatively, other charge-sensitive semiconductor materials may be used, such as molybdenum disulfide, tungsten disulfide, or organic semiconductor films containing silicon or germanium. The thickness of the semiconductor film 102 is relatively thin, for example, the thickness may be less than 50 nanometers. For example, a single-layer graphene film may be used as the graphene.
The source layer 104 and the drain layer 106 are located at both ends of the semiconductor film 102, respectively, and define a channel region of the field FET on the semiconductor film 102. As shown in fig. 2, W represents the width of the channel region, and L represents the length of the channel region, i.e., the spacing between the source layer 104 and the drain layer 106 in the FET. W and L may be set according to actual needs, for example, W and L may satisfy the condition: W/L is more than or equal to 1:2, L is more than or equal to 10 mu m, so that the sensitivity of the chip is improved, and the process requirement is met.
It will be appreciated that there is an overlap between the semiconductor film layer 102 and both the source layer 104 and the drain layer 106, as shown in fig. 2. For example, in consideration of process requirements, the overlapping dimension a between the semiconductor film 102 and the source and drain layers 104 and 106 may be greater than or equal to 2 μm, the upper and lower boundaries of the source and drain layers 104 and 106 may both exceed the semiconductor film 102, and the exceeding dimension b may be greater than or equal to 2 μm.
For example, the source layer 104 and the drain layer 106 may be made of a metal material with good conductivity, such as Au (gold), al (aluminum), mo (molybdenum), or the like.
The protective layer 108 covers the surface of the semiconductor film 102 in the channel region, and the orthographic projection of the channel region on the substrate 100 is located in the orthographic projection of the protective layer 108 on the substrate 100. This can prevent the semiconductor film 102 from directly contacting with the solution to be tested during the test.
On the basis of this, in order to ensure that the semiconductor film 102 as a sensitive layer can sense a change in the charge signal of the object to be measured, the present embodiment provides a sensor layer 110, and the sensor layer 110 has a conductive portion 1101 penetrating the protective layer 108 and contacting the semiconductor film 102 in the channel region. The material of the sensing layer 110 is a material with good conductivity. For example, a metal material such as aluminum or gold or the like may be employed.
Probes are modified on the surface of the sensing layer 110 to form a probe modification layer 112. Probes are used to specifically recognize an analyte, such as a target molecule. In some examples, a Linker molecule (Linker) may be modified between the sensing layer 110 and the probe molecule as a linkage, or alternatively, there may be no Linker. For example, in the case of electrically detecting nucleic acids extracted from tumor cells, peripheral blood samples, or the like, the surface of the sensor layer 110 may be carboxylated, and modified by EDC/NHS chemical reaction with NH 2-modified nucleic acid probe molecules.
The probe modification layer 112 on the surface of the sensing layer 110 contacts with the test solution so that the probe recognizes the test object such as a target molecule in the test solution. Of course, the contact area of the probe modification layer 112 with the solution needs to be smaller than or equal to the area of the upper surface of the sensing layer 110.
The charges generated by the combination of the probe and the object to be detected are transferred to the semiconductor film layer 102 located in the channel region through the conductive part 1101 of the sensing layer 110, so that the semiconductor film layer 102 senses the change of the charge signal of the object to be detected, and the electric detection of the object to be detected in the solution to be detected is realized.
Compared with the mode of directly contacting the semiconductor film 102 with the solution to be detected, the sensing layer 110 has the effects of modifying the probe and transferring charges, the non-specific adsorption effect on impurities in the solution is not as good as that of the semiconductor film 102, the adsorbed impurities are relatively less, the sensitivity on charges is not as strong as that of the semiconductor material, the signal noise can be effectively reduced, the stability and accuracy of the detection result are improved, and the FET electrical detection flow with low signal noise is facilitated.
In some examples, an isolation layer is also disposed between the sensing layer 110 and the probe modification layer 112, the isolation layer having a conductivity lower than the conductivity of the sensing layer 110. Therefore, weak charge changes caused by nonspecific adsorption of impurities can be isolated, and the transfer of obvious charge changes caused by specific adsorption of the probe is not influenced, so that signal noise is further reduced. The electrical conductivity of the barrier material is relatively low, for example, the barrier material may be an oxide, such as TiO 2 、Al 2 O 3 、SiO 2 Or Si (or) 3 NO 4 Etc.
In some examples, the sensing layer 110 may be disposed on a surface of the protective layer 108 covering the channel region, and the front projection of the sensing layer 110 on the substrate 100 is located within the front projection of the channel region on the substrate 100, which is beneficial for reducing the conduction distance of charges, thereby ensuring signal strength, and saving materials. Of course, in other examples, the sensor layer 110 may be disposed at a position other than the channel region on the premise of ensuring that the sensor layer 110 is in contact with the semiconductor film layer 102 of the channel region, which is not limited in this embodiment.
In some examples, the extension direction of the conductive portion 1101 of the sensing layer 110 to the surface of the semiconductor film 102 may be perpendicular to the surface of the substrate 100, which is beneficial to reduce the conduction distance of charges and ensure the signal strength of the signals conducted to the semiconductor film 102. Of course, in other examples, the extending direction of the conductive portion 1101 may also deviate from the direction perpendicular to the substrate 100, which is not limited by the present embodiment.
The gate layer is located between the source layer 104 and the drain layer 106, opposite the channel region, and forms a FET with the source layer 104, the drain layer 106, and the channel region. For example, the material of the gate layer may be a metal with better conductivity, such as Au, al, mo, or the like.
In some examples, the gate layer may include a back gate 122 and a top gate 121, the top gate 121 being disposed on the protective layer 108, the back gate 122 being disposed on the surface of the substrate 100. With this dual gate mode, one of the gates can be grounded during measurement to stabilize the other gate voltage, and the gate voltage is applied to the other gate, as shown in fig. 3, to make the data more stable and reliable. Of course, in other examples, only one of the back gate 122 and the top gate 121 may exist, which is not limited in this embodiment.
For example, considering that the protective layer 108 has a certain thickness, which may be greater than the conventional thickness of the gate dielectric layer, the bottom of the top gate 121 may be embedded within the protective layer 108 to a depth less than the thickness of the protective layer 108 in order not to affect the sensitivity of the FET.
As shown in fig. 1, if the substrate 100 is an n/p doped silicon substrate 100, the back gate 122 may be disposed on a surface of the substrate 100 away from the semiconductor film 102, which facilitates the disposition of the back gate 122. At this time, an insulating layer 101 is further provided between the substrate 100 and the semiconductor film layer 102, and for example, the insulating layer 101 may be a silicon oxide layer.
As shown in fig. 4, if the substrate 100 is a glass-based or undoped silicon-based substrate 100, the back gate 122 may be disposed on a surface of the substrate 100 adjacent to the semiconductor film 102. At this time, an insulating layer 101 is further disposed between the back gate 122 and the semiconductor film layer 102, and for example, the insulating layer 101 may be a silicon oxide layer.
It should be noted that, one or more FET sensing units may be disposed on the substrate 100, and the specific number and arrangement may be set according to actual needs. As shown in fig. 5, when the plurality of FET sensing units 10 are provided, FETs in the plurality of FET sensing units 10 may share the source layer 104, the drain layer 106, and the electrode terminals corresponding to the gate layer, such as the source electrode terminal S, the drain electrode terminal D, and the gate electrode terminal G shown in fig. 5. To improve the integration level. The source electrode terminal S, the drain electrode terminal D, and the gate electrode terminal G are used to connect the signal unit so as to apply the source-drain voltage and the gate voltage at the time of detection. The sensing layers 110 in different FET sensing cells 10 are spaced apart and independent of each other to avoid cross talk of the identification signals. Thus, the electrical detection of different objects to be detected can be realized in the same biological sensing chip.
In particular, a solution to be measured needs to be added to the biosensing chip, so that the solution to be measured contacts with the modified probes on the surface of the sensing layer 110. For example, the solution to be measured may be dropped onto the surface of the sensing layer 110 by a dropping tube or a pipette, and the detection of the object to be measured in the solution to be measured may be performed.
In some examples, the solution to be measured may also be provided to the biosensor chip by microfluidic means. At this time, as shown in fig. 6 and 7, the bio-sensor chip further includes: the sample inlet 132, the sample outlet 133, the microfluidic flow channel 134 and the solution chamber 131 to be tested, wherein the microfluidic flow channel 134 is respectively communicated with the solution chamber 131 to be tested, the sample inlet 132 and the sample outlet 133. The front projection of the solution chamber 131 to be measured on the substrate 100 is located in the front projection of the sensing layer 110 on the substrate 100, so as to ensure that the contact area of the probe modification layer 112 and the solution is smaller than or equal to the area of the upper surface of the sensing layer 110. When in use, the solution to be measured is input from the sample inlet 132, flows into the solution chamber 131 to be measured through the microfluidic flow channel 134, and flows out from the sample outlet 133 through the microfluidic flow channel 134 after the solution chamber 131 to be measured is detected by the probe. Therefore, the detection flow can be conveniently controlled, and the detection efficiency is improved.
For example, the chip further includes a cover plate 130, through holes corresponding to the sample inlet and outlet and grooves corresponding to the microfluidic flow channel 134 and the solution chamber 131 to be tested are provided in the cover plate 130, and the sample inlet 132, the sample outlet 133, the microfluidic flow channel 134 and the solution chamber 131 to be tested can be formed after the cover plate 130 and the substrate 100 are aligned and packaged.
Compared with the traditional FET biological sensing chip, the biological sensing chip provided by the embodiment of the specification avoids the direct contact of the semiconductor material with the solution to be detected in the detection process by additionally arranging the protective layer 108 and the sensing layer 110, reduces the adsorption and interference of impurities, simultaneously senses the change of charge signals of the object to be detected, reduces the signal noise of biological sensing, and effectively improves the stability and accuracy of the detection result.
An exemplary detection process of the graphene FET biosensor chip will be described below with nucleic acids extracted from tumor cells, peripheral blood samples, and the like as an analyte.
PBS buffer, target nucleic acid set sample, and negative nucleic acid set sample were prepared separately. And (3) respectively injecting PBS buffer solution to flush the chip through the sample inlet and the sample outlet, and detecting the change condition of source leakage current along with the gate voltage Vg according to the given source leakage voltage Vds of the circuit shown in figure 3. The grid voltage scanning range can be set according to actual needs and multiple tests. Similarly, the target nucleic acid set sample and the negative nucleic acid set sample are measured separately.
And respectively recording measurement results of the PBS buffer solution group, the target nucleic acid group and the negative nucleic acid group, comparing the change condition of graphene Dirac (Dirac) points in a source leakage current-gate voltage (Ids-Vg) curve before and after detection, and analyzing to obtain a detection result (whether the detection result is negative) of the target nucleic acid group sample.
The biological sensing chip provided by the embodiment of the specification can effectively reduce noise of detection signals, and is used for electrically detecting nucleic acid extracted from tumor cells, peripheral blood samples and the like, so that the biological sensing chip is beneficial to providing rapid, portable and more accurate diagnosis for nucleic acid detection in hot medical fields such as single cell analysis, early cancer diagnosis, prenatal diagnosis and the like.
In a second aspect, embodiments of the present disclosure further provide an analysis device including the biosensing chip provided in the first aspect. Of course, the analysis device may include other structures in addition to the bio-sensor chip. For example, the analyzing apparatus may further include a signal unit for supplying an electric signal to the FET in the bio-sensing chip and detecting the source-drain current signal to obtain a detection result. For another example, the analysis device may further include a microfluidic unit such as a sample inlet and outlet pipe, a pump, etc. to control sample injection and sample discharge of the biosensing chip, and specific reference may be made to the related art, which will not be described in detail herein.
In a third aspect, embodiments of the present disclosure further provide a method for manufacturing a biosensor chip, which is used for manufacturing the biosensor chip provided in the first aspect. As shown in fig. 8, the method includes:
step S101, forming a semiconductor film layer on a substrate;
step S102, forming a source electrode layer and a drain electrode layer to define a channel region on the semiconductor film layer;
step S103, forming a protective layer on the channel region, wherein the orthographic projection of the channel region on the substrate is positioned in the orthographic projection of the protective layer on the substrate;
step S104, forming a sensing layer on the protective layer, and modifying a probe on the surface of the sensing layer, wherein the sensing layer is provided with a conducting part penetrating through the protective layer and contacting with the semiconductor film layer of the channel region, so that charges generated by combining the probe with an object to be tested in the solution to be tested are transferred to the semiconductor film layer through the conducting part;
in step S105, a gate layer is formed between the source layer and the drain layer.
It should be noted that the order of execution of steps S101 to S105 may be the same as that shown in fig. 8, or may be different from that shown in fig. 8, for example, some steps may be executed synchronously, and some steps may be executed before or after other steps, which is not limited in this embodiment.
An exemplary manufacturing process is described below by taking a biosensing chip with a semiconductor film 102 as a graphene layer, a substrate 100 as an n/p heavily doped silicon substrate, and a double gate structure and adopting a microfluidic liquid inlet mode as an example. Specifically, the preparation process can comprise the following preparation procedures:
the preparation flow of the FET silicon substrate comprises the following steps:
silicon oxide (SiO) deposition: a Chemical Vapor Deposition (CVD) process is used to deposit a SiO layer 900A thick on the heavily doped silicon substrate.
Graphene transfer: and (3) uniformly and compactly growing single-layer graphene on the copper foil by using a CVD (chemical vapor deposition) method and the like, supporting a graphene film by using PMMA (polymethyl methacrylate, polymethyl methacrylate, also called acryl or organic glass) to form a sandwich structure of PMMA+graphene+copper foil, and then placing the graphene into ammonium persulfate or ferric chloride solution for etching. And finally transferring the graphene sample onto a silicon-based substrate with a SiO layer, and removing PMMA to obtain the transferred graphene sample.
Back gate 122 preparation: and patterning a metal layer on the back surface of the heavily doped silicon substrate by adopting sputtering coating, photoetching and wet etching processes, wherein the metal layer is made of Al.
Preparing an alignment metal layer: a lift-off (liftoff) process may be used to provide Al as the para-metal layer material.
Patterning graphene: and coating photoresist on the surface of the graphene, patterning the photoresist layer through photoetching (photo) equipment, and then etching the exposed graphene through Plasma (Plasma) etching equipment, so as to strip the photoresist, thereby realizing the patterning of the graphene.
Preparing a source drain metal layer: prepared by a lift-off (liftoff) process, the material is Al.
Protective layer 108 preparation: siO with the thickness of 900A is deposited on graphene through a CVD process, the SiO layer covers the whole graphene channel, and part of source drain metal layers at two ends of the channel region can be further covered, so that the effect of better preventing the graphene from being contacted with a solution is achieved.
Top gate 121 and sense layer 110 preparation: firstly, photoresist is coated on the protective layer 108 opposite to the channel region, the photoresist layer is patterned by photoetching (photo) equipment, and openings are formed in a predetermined top gate region and a predetermined sensing layer region, so that the underlying protective layer 108 is exposed; then the top gate regions are respectively aligned by a reactive ion etching (Reactive Ion Etching, RIE) deviceAnd etching the sensing layer region to form a first etching groove corresponding to the top gate 121 and a second etching groove corresponding to the sensing layer 110. The depth of the first etched trench is less than the thickness of the protective layer 108 and the depth of the second etched trench is equal to the thickness of the protective layer 108, i.e., such that the sensing layer 110 region exposes the underlying graphene layer. Then, metal Al is sputtered by a sputtering coating method, and then photoresist is stripped, so that the top gate 121 and the sensing layer 110 with the conductive part 1101 contacting the graphene layer can be formed. Further, the surface of the sensing layer 110 is subjected to oxidation treatment to form Al 2 O 3 As an isolation layer.
Modification of the probe: to be formed with Al 2 O 3 Carboxylation is performed on the surface of the sensing layer 110, and chemical reaction modification is performed on the surface of the sensing layer through EDC/NHS and a nucleic acid probe molecule for modifying NH 2.
The cover plate 130 preparation process: a negative mold of PDMS is first pattern-prepared, and then a PDMS cover 130 is prepared using the negative mold, and through holes are punched at positions of a sample inlet 132 and a sample outlet 133, respectively, as shown in fig. 9 to 11.
And (3) packaging flow: the FET silicon substrate and cover plate 130 are packaged with a semiconductor device such as a Plasma (Plasma) packaging device.
In the above description, technical details such as patterning of the respective layers of the product are not described in detail. Those skilled in the art will appreciate that layers, regions, etc. of the desired shape may be formed by a variety of techniques. In addition, to form the same structure, those skilled in the art can also devise methods that are not exactly the same as those described above. Although the embodiments are described above separately, this does not mean that the measures in the embodiments cannot be used advantageously in combination.
In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the present application may be practiced without these specific details. In some instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.
In addition, one of ordinary skill in the art will appreciate that: the discussion of any of the embodiments above is merely exemplary and is not intended to suggest that the scope of the disclosure is limited to these examples; combinations of features of the above embodiments or in different embodiments are also possible within the spirit of the present disclosure, steps may be implemented in any order, and there are many other variations of the different aspects of one or more embodiments described above which are not provided in detail for the sake of brevity.
While preferred embodiments of the present description have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the disclosure.
Claims (13)
1. A biosensing chip, comprising:
a substrate;
a semiconductor film layer located on the substrate;
the source electrode layer and the drain electrode layer are respectively positioned at two ends of the semiconductor film layer, and a channel region is defined on the semiconductor film layer;
the protective layer covers the surface of the semiconductor film layer of the channel region, and the orthographic projection of the channel region on the substrate is positioned in the orthographic projection of the protective layer on the substrate;
a sensing layer and a probe modification layer disposed on the sensing layer, the probe modification layer including a probe for identifying an object to be measured in a solution to be measured, the sensing layer having a conductive portion passing through the protective layer and contacting the semiconductor film of the channel region such that charges generated by the probe in combination with the object to be measured are transferred to the semiconductor film through the conductive portion;
and the gate layer is positioned between the source electrode layer and the drain electrode layer and forms a field effect transistor with the source electrode layer, the drain electrode layer and the channel region.
2. The biosensing chip of claim 1, further comprising: the micro-fluid flow channel is respectively communicated with the solution chamber to be detected, the sample inlet and the sample outlet, and the orthographic projection of the solution chamber to be detected on the substrate is positioned in the orthographic projection of the sensing layer on the substrate.
3. The biosensing chip of claim 1, wherein an isolation layer is provided between the sensing layer and the probe modification layer, the isolation layer having a conductivity lower than a conductivity of the sensing layer.
4. The biosensing chip of claim 3, wherein the material of said isolation layer is an oxide, said oxide layer being: tiO (titanium dioxide) 2 、Al 2 O 3 、SiO 2 Or Si (or) 3 NO 4 。
5. The biosensing chip of claim 1, wherein the material of the sensing layer is a metallic material, and the metallic material is aluminum or gold.
6. The biosensing chip of claim 1, wherein an orthographic projection of said sensing layer on said substrate is located within an orthographic projection of said channel region on said substrate.
7. The biosensing chip of claim 6, wherein an extending direction of said conductive portion to a surface of said semiconductor film layer is perpendicular to said substrate.
8. The biosensing chip of claim 1, wherein a plurality of field effect transistors are disposed on the substrate, the plurality of field effect transistors share a source layer, a drain layer and electrode terminals corresponding to a gate layer, and the sensing layers corresponding to the different field effect transistors are disposed at intervals.
9. The biosensing chip of claim 1, wherein the width of the channel region: length greater than or equal to 1:2, the length of the channel region is greater than or equal to 10 microns, wherein the length is the spacing between the source layer and the drain layer.
10. The biosensing chip of claim 1, wherein the material of the semiconductor film layer may be any one of the following materials:
graphene, molybdenum disulfide, tungsten disulfide, and organic semiconductor thin films containing silicon or germanium.
11. The biosensing chip of claim 1, wherein said gate layer comprises a back gate and a top gate, said top gate being disposed on said protective layer, said back gate being disposed on said substrate surface.
12. A method of manufacturing a biosensing chip, the method comprising:
forming a semiconductor film layer on a substrate;
forming a source electrode layer and a drain electrode layer to define a channel region on the semiconductor film layer;
forming a protective layer on the channel region, wherein the orthographic projection of the channel region on the substrate is positioned in the orthographic projection of the protective layer on the substrate;
forming a sensing layer on the protective layer, and modifying a probe on the surface of the sensing layer, wherein the sensing layer is provided with a conducting part penetrating through the protective layer and contacting with a semiconductor film layer of the channel region, so that charges generated by combining the probe and an object to be detected in a solution to be detected are transferred to the semiconductor film layer through the conducting part;
a gate layer is formed between the source and drain layers.
13. An analysis device, comprising: the biosensing chip of any one of claims 1-11.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210886197.8A CN117497588A (en) | 2022-07-26 | 2022-07-26 | Biological sensing chip, preparation method thereof and analysis device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210886197.8A CN117497588A (en) | 2022-07-26 | 2022-07-26 | Biological sensing chip, preparation method thereof and analysis device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117497588A true CN117497588A (en) | 2024-02-02 |
Family
ID=89671363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210886197.8A Pending CN117497588A (en) | 2022-07-26 | 2022-07-26 | Biological sensing chip, preparation method thereof and analysis device |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117497588A (en) |
-
2022
- 2022-07-26 CN CN202210886197.8A patent/CN117497588A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10059982B2 (en) | Nano-sensor array | |
| Reddy et al. | High-k dielectric Al 2 O 3 nanowire and nanoplate field effect sensors for improved pH sensing | |
| US9810660B2 (en) | Fin-FET sensor with improved sensitivity and specificity | |
| US9228974B2 (en) | Biosensing well array by self-alignment and selective etching | |
| KR101056385B1 (en) | Detection element | |
| US9759681B2 (en) | Biomolecule detection method, biomolecule detection device and analysis device | |
| US10126263B2 (en) | Wide dynamic range fluid sensor based on nanowire platform | |
| US7632670B2 (en) | Fet sensor with specially configured gate electrode for the highly sensitive detection of analytes | |
| CN107356649B (en) | Multi-channel biosensor and manufacturing method thereof | |
| US20160202208A1 (en) | Multiplexing detection system of dual gate ion-sensitive field-effect transistor sensor | |
| Chen et al. | Contacting versus insulated gate electrode for Si nanoribbon field-effect sensors operating in electrolyte | |
| EP3180606A1 (en) | Electrolyte-gated transistors for detection of molecules | |
| JP5903872B2 (en) | Transistor type sensor and method for manufacturing transistor type sensor | |
| CN117497588A (en) | Biological sensing chip, preparation method thereof and analysis device | |
| WO2020000169A1 (en) | Sample analysis chip and fabricating method thereof | |
| CN205175960U (en) | Measurement device for biomacromolecule charge -mass ratio | |
| Bhatt et al. | Dual‐gate ion‐sensitive field‐effect transistors: A review | |
| CN114689672B (en) | Systems and methods for detecting biomolecules | |
| TWI832146B (en) | Solution-gated graphene transistor with dual gates | |
| JP5472013B2 (en) | Transistor type sensor | |
| US11662331B2 (en) | Nanobio sensing device | |
| US11715772B1 (en) | Field-controlled sensor architecture and related methods | |
| WO2015088055A1 (en) | Bio-sensor using single electron transistor operating at room temperature, method for manufacturing same, analysis system having same, and analysis method | |
| CN116936640A (en) | Ion sensitive thin film transistor and biosensing chip | |
| CN115963161A (en) | Carbon nanotube field effect transistor biosensor of wavy sensing interface, preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |