CN113418976A - Femtomolar concentration detection method of microliter-scale glucose-containing sample liquid to be detected - Google Patents
Femtomolar concentration detection method of microliter-scale glucose-containing sample liquid to be detected Download PDFInfo
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- 239000008103 glucose Substances 0.000 title claims abstract description 92
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 title claims abstract description 90
- 238000001514 detection method Methods 0.000 title claims abstract description 39
- 239000007788 liquid Substances 0.000 title claims abstract description 29
- 239000000523 sample Substances 0.000 claims abstract description 36
- 239000010409 thin film Substances 0.000 claims abstract description 36
- 239000012488 sample solution Substances 0.000 claims abstract description 22
- 239000004065 semiconductor Substances 0.000 claims abstract description 14
- 108010015776 Glucose oxidase Proteins 0.000 claims abstract description 9
- 239000004366 Glucose oxidase Substances 0.000 claims abstract description 9
- 229940116332 glucose oxidase Drugs 0.000 claims abstract description 9
- 235000019420 glucose oxidase Nutrition 0.000 claims abstract description 9
- 238000002347 injection Methods 0.000 claims abstract description 7
- 239000007924 injection Substances 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 23
- 229910052961 molybdenite Inorganic materials 0.000 claims description 21
- 229910052982 molybdenum disulfide Inorganic materials 0.000 claims description 21
- 230000035945 sensitivity Effects 0.000 claims description 9
- 239000010408 film Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 7
- 238000012546 transfer Methods 0.000 claims description 4
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- 238000005229 chemical vapour deposition Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000005566 electron beam evaporation Methods 0.000 claims description 2
- 230000005669 field effect Effects 0.000 claims description 2
- 238000001259 photo etching Methods 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 15
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 8
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 8
- 235000010323 ascorbic acid Nutrition 0.000 description 8
- 229960005070 ascorbic acid Drugs 0.000 description 8
- 239000011668 ascorbic acid Substances 0.000 description 8
- 239000004202 carbamide Substances 0.000 description 8
- 229940116269 uric acid Drugs 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 229940045136 urea Drugs 0.000 description 7
- 239000011259 mixed solution Substances 0.000 description 5
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- 238000000605 extraction Methods 0.000 description 4
- 239000000120 Artificial Saliva Substances 0.000 description 3
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 238000002474 experimental method Methods 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 210000004243 sweat Anatomy 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 238000011840 criminal investigation Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
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- 239000002904 solvent Substances 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4145—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
-
- 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
- B01L3/502—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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/414—Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- G01N27/4148—Integrated circuits therefor, e.g. fabricated by CMOS processing
Abstract
A femtomolar concentration detection method of microliter-scale glucose-containing sample liquid to be detected belongs to the technical field of biosensor application. The detection precision of the prior art is only in mM magnitude, and the dosage of the sample solution to be detected is also in mL magnitude. The invention is characterized in that firstly, MoS is mixed2The thin film FET and the micro-fluidic chip are integrated into a micro-fluidic electrochemical sensing chip; secondly, injecting microliter volume-level sample liquid containing glucose and added with glucose oxidase into the microfluidic electrochemical sensing chip through a microfluidic chip channel by using a micro digital injection pump; thirdly, according to the drain current I output by the semiconductor parameter analyzerdsAnd judging the concentration of the sample liquid containing glucose to be detected, wherein the concentration is fM concentration magnitude, the required sample liquid to be detected only needs 3-5 mu L, and the trace detection can be realized.
Description
Technical Field
The invention relates to a femtomolar concentration detection method of microliter-scale glucose-containing sample liquid to be detected, belonging to the technical field of biosensor application.
Background
In the prior art, there is a name of "employing MoS2Technical scheme of method for detecting concentration of glucose solution by using thin film FET (ZL201641612. X), which uses MoS2Fixing the film FET in a sample tank containing PBS solution, starting a semiconductor parameter analyzer to measure zero-concentration MoS2Drain current I of thin film FETds(ii) a Using PBS solution as solvent, preparing a plurality of glucose solutions with different concentrations within the concentration range of 1-30 mM, and mixing the glucose solutions with glucose oxidase GOxSequentially adding the glucose solution into the sample tank, and detecting MoS corresponding to each glucose solution with a certain concentration one by a semiconductor parameter analyzer2Drain current I of thin film FETds(ii) a From the aforementioned respective drain currents IdsEstablishing a detection basic database in a combined manner; in the actual measurement, PBS solution with known volume, glucose solution to be measured with known volume but unknown concentration and glucose oxidase GO are mixedxAdded together into the sample tank according to the MoS measured by the semiconductor parameter analyzer at that time2Drain current I of thin film FETdsAnd combining the detection basic database, and converting to obtain the concentration of the detected glucose solution. However, this solution presents two technical problems. On the one hand, this solution is to detect in an open system, whether MoS as an electrochemical sensor2The film FET or the glucose solution as the sample solution is placed in the sample tank, and external environmental factors, such as dust in the air and air humidity, inevitably affect the detection result, so that the detection sensitivity is reduced, the concentration of the sample solution capable of being detected is in the millimole level, and if the concentration range of the detected glucose solution is 1 mM-30 mM (millimole per liter), the glucose content of some sample solutions to be detected is extremely low, the concentration is in the fM (femtomole per liter) level, and the interference of complex components of the sample solution to be detected is added, the existing scheme is difficult to adequately detect. On the other hand, in this embodiment, the MoS is used as an electrochemical sensor2The thin film FET is contacted with a glucose solution as a sample solution in a sample tank, the dosage of the sample solution is in milliliter order, and if the basic dosage of the detected glucose solution is 0.1-0.2 mL, blood is taken as the sample solution to be detectedIn the prior art, the amount of the sample liquid to be detected is not limited to the non-invasive detection, and the non-invasive detection can be realized by collecting saliva, urine and sweat, however, the extraction amount is usually only in the microliter level, such as the extraction of sweat, and in some occasions, even if saliva and urine are used, the required basic detection amount is difficult to obtain, such as the extraction of the sample liquid to be detected in the criminal investigation process, so that the extraction amount of the sample liquid to be detected becomes the difficulty faced by the existing scheme.
In the prior art, a technical scheme for integrating the FET and the microfluidic chip to realize specific detection in the fields of biology, chemistry and medicine is provided, the detection is accurate, the sample consumption is less, the response speed is high, and the interference of external environmental factors on the FET sensor can be isolated. However, the FET is not MoS2Thin film FETs, which are not used for glucose solution concentration detection, and MoS2The technical advantages of thin film FETs in the detection of glucose solution concentration are not available from other prior art techniques, e.g., due to MoS2The film is a direct band gap, the forbidden bandwidth is gradually reduced along with the increase of the layer number, and the MoS2The thin film FET has advantages of a large switching current ratio, high carrier mobility, high sensitivity, and the like.
Disclosure of Invention
In order to improve the detection precision of the glucose concentration of a sample solution to be detected and complete detection under the condition of only trace amount of the sample solution to be detected, a femtomolar concentration detection method of the sample solution to be detected containing glucose in microliter level is invented.
The method for detecting femtomolar concentration of microliter-scale glucose-containing sample liquid to be detected is characterized in that firstly, MoS is added2The thin film FET and the micro-fluidic chip are integrated into a micro-fluidic electrochemical sensing chip; secondly, injecting microliter volume-level sample liquid containing glucose and added with glucose oxidase into the microfluidic electrochemical sensing chip through a microfluidic chip channel by using a micro digital injection pump; thirdly, according to the drain current I output by the semiconductor parameter analyzerdsAnd judging the concentration of the glucose-containing sample solution to be detected, wherein the concentration is fM concentration magnitude.
The technical effects of the present invention are as follows.
The invention relates to MoS2Thin film FET as an enzyme biosensor is integrated with a microfluidic chip due to MoS2The film FET has the technical advantages in the aspect of detecting the concentration of the glucose solution and the technical characteristics of the microfluidic chip in the aspect of biological detection, fM concentration magnitude detection of the glucose concentration can be realized by adopting microliter-magnitude sample liquid to be detected, the glucose concentrations of the sample liquid to be detected are different, Ids-UdsThe trend of the relation curve is close to but different from that of the relation curve, and the trend corresponds to a certain drain-source voltage U along with the increase of the glucose concentrationdsThe value, e.g. 5V, corresponding exactly to a gradually increasing drain-source current IdsThe value, as shown in FIG. 1, from which the glucose concentration C of the sample liquid to be measured was measuredgThe value of (c).
Because the micro-fluidic chip takes the micro-pipeline network as a structural characteristic, the sample liquid flow is controllable, the consumption is very little, the channel and the reaction chamber with the micron scale are relatively closed, the interference of various environmental factors including water vapor and dust can be effectively avoided, the detection sensitivity is obviously improved compared with the prior art, and the detection of the glucose concentration can be finished only by 5 mu L of sample liquid to be detected.
By using the method of the present invention, when the glucose concentration C of the sample solution to be measuredgMoS is known and is 10fM2Drain-source current I of thin film FETdsNo change, and when the glucose concentration of the sample solution to be measured is 20fM, the drain-source current IdsThe apparent change, as shown in FIG. 2, i.e., the detection limit can be as low as 20fM, illustrates the high detection sensitivity of the present invention, which is experimentally and computationally derived from MoS2The sensitivity S of the microfluidic electrochemical sensing chip with the integrated thin film FET and the microfluidic chip is 9.7936 muA/fM, and the glucose concentration can be detected in the linear range of 20 fM-100 fM. In contrast to the prior art MoS2The sensitivity S of the thin film FET is only 36.5 muA/mM, and the detection linear range is only 1 mM-30 mM.
The Glucose (GLU) -containing sample solution to be tested which is actually used in medicine and biological detection often contains Ascorbic Acid (AA), Urea (UR) and Uric Acid (UA), and the invention is adoptedWhen the method is used for detecting the glucose concentration of the sample liquid to be detected, the response performance is still good under the condition that the interference substances exist, and the detection can still be normally finished. The effect can be verified by another experiment, when the method is used for detecting the glucose solution, the ascorbic acid solution, the uric acid solution and the urea solution with the concentration of 1nM (nanomole per liter), the U-source voltage is along with the U-source leakage voltagedsDuring the detection of the glucose solution, the drain-source current IdsRapidly increases, and the drain-source current I is in the process of detecting ascorbic acid solution, uric acid solution and urea solutiondsOnly a small and slow increase is shown in fig. 3, which illustrates that the detection sensitivity of the method of the present invention for glucose is much higher than that of ascorbic acid, urea and uric acid, so that the method has anti-interference performance. The effect can be verified by another experiment, the four sample liquids to be detected are sequentially mixed solution with the concentration of 1nM ascorbic acid and the concentration of 1nM glucose, mixed solution with the concentration of 1nM urea and the concentration of 1nM glucose, mixed solution with the concentration of 1nM uric acid and the concentration of 1nM glucose, and mixed solution with the concentration of 1nM ascorbic acid, the concentration of 1nM urea, the concentration of 1nM uric acid and the concentration of 1nM glucose, and the I concentrations of the four sample liquids to be detected are detected by adopting the method of the inventionds-UdsThe trend of the dependence curves is almost related to the I of an elemental solution with a glucose concentration of 1nMds-UdsThe trend of the relationship curves is the same, and as shown in fig. 4, it is demonstrated that the presence of interfering substances such as ascorbic acid, urea, and uric acid has almost no influence on the detection of glucose concentration.
The glucose concentration in saliva of healthy people is in the range of 30-80 mu M (micromole per liter), the glucose concentration in urine of healthy people is less than 2.8mM/24h, and the method of the invention capable of detecting fM concentration level glucose solution is completely suitable for detecting the glucose concentration in saliva and urine, for example, artificial urine with the glucose concentration of 2.8mM and artificial saliva with the glucose concentration of 80 mu M are respectively prepared, and the components of the artificial urine and the artificial saliva are complex, so that leakage source current I can be causeddsIf the sample is too large, the sample is respectively diluted by 100 times, and in the process of detecting the sample by adopting the method of the invention, the I of two artificial sample liquids to be detectedds-UdsRelationships betweenThe trend of the curve is almost equal to the I of the glucose simple substance solutionds-UdsThe trend of the relation curves is the same as that shown in fig. 5, so that saliva and urine can be used for replacing blood to detect the glucose content of the human body, and noninvasive detection of the glucose content of the human body is realized.
Although the volume of the reaction chamber of the microfluidic chip is only 5 muL, the volume of the sample liquid to be detected which can be introduced is also only 5 muL, however, MoS is caused2The response time of the thin film FET to glucose is very short, and the detection result can be obtained in a very short time by using the microfluidic electrochemical sensing chip integrated with the thin film FET to detect. For example, in the experiment, 5 μ L of glucose solution with a certain concentration value is introduced into the reaction chamber of the microfluidic chip, and the test results are given by the semiconductor parameter analyzer at the time points of 1s, 2s, 3s and 4s after introduction, as shown in fig. 6, four strips Ids-UdsThe trends of the relation curves are very close, which shows that the microfluidic electrochemical sensing chip can give a response within 1s, so to speak, the response time is less than 1s, and the rapid detection is still realized.
Drawings
FIG. 1 shows I for a set of glucose solutions of different concentrations in the range of 10fM to 100fMds-UdsThe relationship is a graph. FIG. 2 shows the concentration C of glucose solution in the concentration range of 10fM to 100fMgAnd drain-source current IdsThe corresponding relation graph is taken as an abstract figure at the same time. FIG. 3 is I of an elemental glucose solution and an elemental solution of three interfering substancesds-UdsThe relationship curves are compared. FIG. 4 is I of a solution of elemental glucose and a mixed solution of four glucose and an interfering substanceds-UdsThe relationship curves are compared. FIG. 5 is I of artificial urine and artificial saliva containing glucoseds-UdsThe relationship is a graph. FIG. 6 shows the I times of the PBS solution without glucose and the glucose solution with a certain concentration in the time range of 1 s-4 sds-UdsThe relationship curves are compared.
Detailed Description
The specific implementation of the femtomolar detection method of microliter-scale glucose-containing sample solution to be detected in the invention is as follows.
MoS2And (5) manufacturing the thin film FET. MoS manufacturing method by adopting chemical vapor deposition method2Film, FET electrode pattern, Si/SiO using L-edge software2The substrate size is 1X 1cm2The width of the channel is 5 μm; manufacturing a drain-source electrode by using an electron beam evaporation technology after photoetching, wherein the structure of the drain-source electrode is Au/Ni, and the thickness of the drain-source electrode is 70nm/10 nm; MoS is transferred by wet transfer technology2Transferring the film to a drain-source electrode channel; and manufacturing a back gate electrode on the back surface of the device by using quick-drying silver paste.
MoS2Testing of thin film FETs. Testing of fabricated MoS with semiconductor parametric analyzer2The fundamental electrical properties of a thin film FET, on the one hand, yield an output characteristic curve, i.e., Ids-UdsRelationship curves, and transfer characteristic curves, i.e. Ids-UgsRelation curve of Ids-UdsGate voltage U can be known from the relation curvegsThe device has good device control function; on the other hand, obtaining the MoS2Electrical parameters of the thin film FET: field Effect mobility μ of 22.22cm2V-1s-1On-off current ratio of 103The threshold voltage was 9.57V. The produced MoS can be known from the test results2The thin film FET is suitable for detecting the glucose concentration of the solution.
And (3) hooking and initially detecting the microliter-level glucose-containing sample solution concentration detection device. The produced MoS2The thin film FET and a commercial microfluidic chip are integrated into a microfluidic electrochemical sensing chip; connecting a micro digital injection pump with a microfluidic chip, and connecting a semiconductor parameter analyzer with the manufactured MoS2The thin film FET is connected with a liquid transferring gun, an injector and a centrifuge tube; the injector sucks PBS solution, and then the PBS solution is injected into the micro-fluidic chip channel by a micro-digital injection pump until MoS2A thin film FET induction area, starting a semiconductor parameter analyzer to measure the zero concentration MoS of the glucose2Drain current I of thin film FETdsIs 8.92 multiplied by 10-5A, as shown in FIG. 2.
And (3) detecting the sensitivity of the microfluidic electrochemical sensing chip. Ten parts of the components with the concentration of sequentially being prepared within the concentration range of 10fM to 100fMRespectively taking 3-5 mu L of glucose solutions of 10fM, 20fM, 30fM, 40fM, 50fM, 60fM, 70fM, 80fM, 90fM and 100fM, and then respectively injecting the glucose solutions and 0.3-0.5 mu L of glucose oxidase into MoS2Thin film FET sensing region whose MoS is outputted in portions by a semiconductor parameter analyzer2Drain current I of thin film FETdsAs shown in FIG. 2, and zero concentration of MoS glucose2Drain current I of thin film FETdsBy contrast, it can be seen that the drain current I is as low as 10fM for glucose solutionsdsDrain current I at zero glucose concentrationdsAlmost the same, drain current I at a concentration of 20fM in the glucose solutiondsThe detection limit of the microfluidic electrochemical sensing chip in the method of the invention is 20 fM.
And actually measuring the glucose concentration of the sample solution to be measured. Injecting 3-5 mu L of sample liquid to be detected containing glucose and 0.3-0.5 mu L of glucose oxidase into the microfluidic electrochemical sensing chip through a microfluidic chip channel by using a micro digital injection pump; according to the drain current I output by the semiconductor parameter analyzerdsAnd judging the concentration of the glucose-containing sample solution to be detected, wherein the concentration is fM concentration magnitude.
Claims (5)
1. The method for detecting femtomolar concentration of microliter-scale glucose-containing sample liquid to be detected is characterized in that firstly, MoS is added2The thin film FET and the micro-fluidic chip are integrated into a micro-fluidic electrochemical sensing chip; secondly, injecting microliter volume-level sample liquid containing glucose and added with glucose oxidase into the microfluidic electrochemical sensing chip through a microfluidic chip channel by using a micro digital injection pump; thirdly, according to the drain current I output by the semiconductor parameter analyzerdsAnd judging the concentration of the glucose-containing sample solution to be detected, wherein the concentration is fM concentration magnitude.
2. The method of claim 1, wherein the MoS is a femtomolar concentration of the microliter-scale glucose-containing test sample solution2The manufacturing process of the thin film FET comprises the following steps: MoS manufacturing method by adopting chemical vapor deposition method2Film, FET electrode pattern, Si/SiO using L-edge software2The substrate size is 1X 1cm2The width of the channel is 5 μm; manufacturing a drain-source electrode by using an electron beam evaporation technology after photoetching, wherein the structure of the drain-source electrode is Au/Ni, and the thickness of the drain-source electrode is 70nm/10 nm; MoS is transferred by wet transfer technology2Transferring the film to a drain-source electrode channel; and manufacturing a back gate electrode on the back surface of the device by using quick-drying silver paste.
3. The method of claim 2, wherein the MoS is a MoS model of a micro-liter of a sample solution containing glucose to be tested2The testing process of the thin film FET is as follows: testing of fabricated MoS with semiconductor parametric analyzer2The fundamental electrical properties of a thin film FET, on the one hand, yield an output characteristic curve, i.e., Ids-UdsRelationship curves, and transfer characteristic curves, i.e. Ids-UgsRelation curve of Ids-UdsGate voltage U can be known from the relation curvegsThe device has good device control function; on the other hand, obtaining the MoS2Electrical parameters of the thin film FET: field Effect mobility μ of 22.22cm2V-1s-1On-off current ratio of 103The threshold voltage was 9.57V.
4. The method for detecting the femtomolar concentration of the microliter-scale glucose-containing sample liquid to be detected according to claim 1, wherein the detection sensitivity of the microfluidic electrochemical sensing chip is determined by the following steps: preparing ten parts of glucose solutions with the concentrations of 10fM, 20fM, 30fM, 40fM, 50fM, 60fM, 70fM, 80fM, 90fM and 100fM in sequence within the concentration range of 10 fM-100 fM, sequentially and respectively taking 3-5 mu L, and sequentially and respectively injecting the glucose solutions and 0.3-0.5 mu L of glucose oxidase into MoS2Thin film FET sensing region whose MoS is outputted in portions by a semiconductor parameter analyzer2Drain current I of thin film FETdsAnd zero concentration of glucose MoS2Drain current I of thin film FETdsIn contrast, drain current I at glucose solution concentrations as low as 10fMdsDrain current I at zero glucose concentrationdsAlmost same as glucoseDrain current I at a glucose solution concentration of 20fMdsThe detection limit of the microfluidic electrochemical sensing chip in the method of the invention is 20 fM.
5. The method for detecting the femtomolar concentration of the microliter-scale glucose-containing sample liquid to be detected according to claim 1, wherein a micro-digital injection pump is adopted to inject 3-5 μ L of the sample liquid to be detected containing glucose and 0.3-0.5 μ L of glucose oxidase into the microfluidic electrochemical sensing chip through a microfluidic chip channel.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5543024A (en) * | 1987-03-03 | 1996-08-06 | Mitsubishi Denki Kabushiki Kaisha | Glucose sensitive FET sensor and method of making same |
| CN103558268A (en) * | 2013-09-04 | 2014-02-05 | 盐城工学院 | Method for electrochemically detecting concentration of glucose in whole blood through integrated paper based micro-fluidic apparatus |
| CN107037108A (en) * | 2016-10-26 | 2017-08-11 | 长春理工大学 | Using MoS2The method that film F ET detects glucose concentration |
| CN107051601A (en) * | 2017-06-06 | 2017-08-18 | 河南理工大学 | Detection of nucleic acids micro-fluidic chip and preparation method based on graphene field effect pipe |
| CN111751523A (en) * | 2020-06-30 | 2020-10-09 | 清华大学深圳国际研究生院 | Biochemical index detection device based on micro-fluidic chip and smart phone |
-
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- 2021-06-03 CN CN202110620438.XA patent/CN113418976A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5543024A (en) * | 1987-03-03 | 1996-08-06 | Mitsubishi Denki Kabushiki Kaisha | Glucose sensitive FET sensor and method of making same |
| CN103558268A (en) * | 2013-09-04 | 2014-02-05 | 盐城工学院 | Method for electrochemically detecting concentration of glucose in whole blood through integrated paper based micro-fluidic apparatus |
| CN107037108A (en) * | 2016-10-26 | 2017-08-11 | 长春理工大学 | Using MoS2The method that film F ET detects glucose concentration |
| CN107051601A (en) * | 2017-06-06 | 2017-08-18 | 河南理工大学 | Detection of nucleic acids micro-fluidic chip and preparation method based on graphene field effect pipe |
| CN111751523A (en) * | 2020-06-30 | 2020-10-09 | 清华大学深圳国际研究生院 | Biochemical index detection device based on micro-fluidic chip and smart phone |
Non-Patent Citations (2)
| Title |
|---|
| BYUNGHOON RYU ET AL.: "Cycle-Wise Operation of Printed MoS2 Transistor Biosensors for Rapid Biomolecule Quantification at Femtomolar Levels", 《ACS SENSORS》 * |
| 单俊杰: "二硫化钼薄膜及其光电器件的制备和性质研究", 《中国优秀博硕士学位论文全文数据库(博士)信息科技辑》 * |
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