CN109061196A - A method of based on nano silicon particles-mass spectrum joint-detection insulin - Google Patents
A method of based on nano silicon particles-mass spectrum joint-detection insulin Download PDFInfo
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- CN109061196A CN109061196A CN201811115773.9A CN201811115773A CN109061196A CN 109061196 A CN109061196 A CN 109061196A CN 201811115773 A CN201811115773 A CN 201811115773A CN 109061196 A CN109061196 A CN 109061196A
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
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- G01N33/6851—Methods of protein analysis involving laser desorption ionisation mass spectrometry
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- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
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Abstract
The invention belongs to the technical fields of insulin detection, in particular to a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, the method includes insulin antibody coatings to pass through the silicon nano of GLYMO progress functional modification, insulin in immunity enrichment sample, PBS washing removes unbonded sample component and non-specific sample, the nano silicon particles for being enriched insulin are added dropwise on MALDI target plate again, carry out insulin detection using MALDI-TOF MS.The present invention uses MALDI-TOF MS joint nano silicon particles to complete the foundation to insulin detection method for the first time；The advantages that this method is especially suitable for the insulin in blood serum sample, and detection method provided by the invention has required sample size small, high sensitivity, accurate stable, fast and convenient and high-throughput.
Description
Technical field
It is the invention belongs to the technical field of insulin detection, in particular to a kind of based on nano silicon particles-mass spectrum joint inspection
The method for surveying insulin.
Background technique
Insulin is the important substance for adjusting body fat and carbohydrate metabolism, and the detection of insulin has many heavy
The clinical meaning wanted, insulin detection have an important role for the research of glycometabolism disease, especially hypoglycemosis because
Analysis, the study of incident mechanism and assessment islet β cell function aspect of diabetes have important role, wherein dynamic
Detection β cell deposit insulin facilitates the clinical state of an illness and therapeutic scheme for determining diabetes.
The common method of laboratory testing insulin mainly has radio immunoassay (RIA), ELISA at present
Method, chemiluminescence immunoassay (CLIA), Electrochemiluminescence assay (ECLIA) etc., these detection methods or detection
For system when detecting insulin, there is deficiencies for detection speed, sensitivity, specificity and stability etc., use these
Data may carry out auxiliary diagnosis using insulin testing result to clinic and treatment detection brings adverse effect.
Matrix-assisted laser desorption ionization (MALDI-TOFMS) is since its detection is quick, easy, high pass
The features such as amount, is widely used among the sample detection of biomolecule, however, when being detected with traditional approach to insulin
When, it has been found that mass spectrum is difficult to detect the data of insulin, therefore, how to establish a kind of high-throughput mass spectrum rapid quantitative detection pancreas
The method of island element becomes insulin detection field technical problem urgently to be solved.
Summary of the invention
High-throughput mass spectrography fast quantification is assisted using nano-silicon in view of the deficiencies of the prior art, the present invention provides a kind of
The method for detecting insulin, high sensitivity, high specificity, stability are good.
In order to solve the above technical problems, the purpose of the present invention is achieved by following technical proposals:
A method of based on nano silicon particles-mass spectrum joint-detection insulin, the method includes insulin antibody packets
By silicon nano, insulin in immunity enrichment sample, washing removes unbonded sample component and non-specific sample, then
The nano silicon particles for being enriched insulin are added dropwise on MALDI target plate, carry out insulin detection using MALDI-TOFMS.
Above-mentioned silicon nano carries out functionalization by 3- glycidyl ether oxypropyltriethoxysilane (GLYMO) and repairs
Decorations, then be coated with insulin antibody.
The dosage of above-mentioned insulin antibody is 10-30 μ g, preferably 15 μ g.
The type of above-mentioned sample is serum or blood plasma, preferably serum.
The matrix of above-mentioned MALDI detection insulin is selected from alpha-cyano -4- hydroxycinnamic acid (CHCA), 2,5- dihydroxy benzenes first
Sour (DHB) or erucic acid (SA), preferably alpha-cyano -4- hydroxycinnamic acid (CHCA).
Above-mentioned washing process uses phosphate buffer (PBS).
In order to increase the signal of insulin, there are mainly two types of methods, and one is label insulin derivates, another kind is to see
Different nano materials is examined, if magnetic bead, graphene, nano silicon particles, silver nano-grain and mesoporous silicon are as matrix.For first
Kind method, with dansyl Cl, 6- aminoquinoline base-N- hydroxysuccinimidyl acylimino formic acid esters, ayapanin -3- carboxylic acid
Chemical derivatization substance of the N- succinimide ester as label insulin, shows that they cannot enhance pancreas islet by chemical modification
Plain MS signal；For second method, all these nano particles all have the potentiality as MALDI common substrate, pass through increasing
Desorption/ionization of peptide is added to enhance MS signal, the experimental results showed that, nano silicon particles and magnetic bead can effectively increase insulin letter
Number.However, insulin signaling is unstable when using magnetic bead as co-substrate.Therefore, nano silicon particles are enhancing insulin letter
Number optimal selection.
In order to select suitable sample type, by detecting multiple groups clinical sample, more different sample type (serum and blood
Slurry) measurement insulin concentration, the results show that serum and blood plasma can detect effective signal, but the letter of serum insulin
Number be higher than blood plasma, therefore, serum is the sample type detected more suitable for this method.
In order to select the dosage of coated antibody, by the different sample of detection multiple groups antibody dosage, the results show that working as antibody
When amount is 10-30 μ g, effective signal can be obtained, comprehensively consider dosage and signal strength, 15 μ g are optimum amount.
In order to select MALDI detection insulin most suitable matrix, by using alpha-cyano -4- hydroxycinnamic acid (CHCA),
2,5-dihydroxybenzoic acid (DHB) and erucic acid (SA) are that matrix carries out insulin measurement, the results show that effective letter can be obtained
Number, but the signal of CHCA is most strong, therefore CHCA is the optimum substrate of this insulin measuring table.
Compared to the prior art the present invention, has the following beneficial effects:
1, present invention firstly discovers that nano silicon particles as detection matrix to insulin Mass Spectrometer Method, there is enhancing mass spectrum
The effect of signal.
2, the present invention completes the foundation to insulin detection method using MALDI-TOFMS joint nano silicon particles for the first time.
3, detection method provided by the invention, required sample size are small, it is only necessary to and detection can be completed in the sample volume of 100 μ L,
Detection operation is very fast and convenient, and flux is high.
4, detection method high sensitivity provided by the invention, quantitative detection limit (LOQ) down to 0.1nM, detect signal strength
It is in good linear relationship with insulin concentration, linear regression coeffficient (R2) is 0.99, analyzes interior precision (the % coefficient of variation)
It is 1.81%~4.53%, precision is 2.71%~8.09% between analysis, in addition, MALDI measurement and chemiluminescence immunoassay point
Analysis (CIA) consistency detection is completed in clinical samples, and it is obtained wear it is bright recurrence show good consistency (R2
=0.981).
Detailed description of the invention
Fig. 1 be nano particle of the invention different as co-substrate when insulin signaling；
Fig. 2 is the insulin signaling figure of present invention detection validity；
Fig. 3 is the insulin signaling figure of different sample types of the invention；
Fig. 4 is the insulin signaling figure of different antibodies dosage of the present invention；
Fig. 5 is the insulin signaling figure of different substrates of the present invention；
Fig. 6 is the result figure of present invention detection limit experiment；
Fig. 7 is another result figure of present invention detection limit experiment；
Fig. 8 is the result figure of Linear Experiment of the present invention；
Fig. 9 is that detection method of the invention wears bright regression figure compared with chemiluminescence immune analysis method.
Specific embodiment
By the description of specific embodiment, the invention will be further described with reference to the accompanying drawing, and following embodiment is not
It is limitation of the present invention, those skilled in the art's basic thought according to the present invention, various modifications may be made or improves,
As long as they do not deviate from the basic of the present invention, it is all within the scope of the present invention:
MALDI-TOFMS used in the embodiment of the present invention are as follows: the production of dalton Brooker company of the U.S.
The desk-top matrix solid-dispersion time of-flight mass spectrometer of microflex series.
Used silicon nanoparticle is purchased from ocean nanometer scientific & technical corporation (U.S.)；Rh-insulin is international public purchased from peptide
It takes charge of in (U.S.)；Anti-Human Insulin's antibody is purchased from Abcam (U.S.)；Other nano particles are purchased from ocean nanometer scientific & technical corporation (beauty
State)；Magnetic bead is purchased from the silent winged generation that (U.S.) of match；Other reagents such as acetonitrile, trimethoxy silane are purchased from SigmaAldrich (beauty
State).
Mass Spectrometer Method condition of the present invention are as follows: matched MALDI detection parameters are as follows: UnisonUK-C8guard-column,
2.0i.d.×_5mm,IntaktCorpora-tion。
Detection method is as follows: silicon nano carries out functional modification by CLYMO, and insulin antibody is coated with silicon nanoparticle
Son, the insulin in immunity enrichment sample, washing remove unbonded sample component and non-specific sample, washing and use PBS
(0.01mol/L), then the nano silicon particles for being enriched insulin are added dropwise on MALDI target plate, dry under N2 stream, last benefit
Insulin detection is carried out with MALDI-TOFMS.
Above-mentioned silicon nano carries out the concrete operation step of functional modification by CLYMO are as follows: silicon nano (70
Hundred million/pipe) it is centrifuged 20 minutes at 4000g, it is dried in vacuo, is suspended in 3mL dimethyl sulfoxide, rotation mixing 1 is small at room temperature
When；Silicon nano is pelletized 20 minutes at 4000g, ethanol washing 3 times, is mixed at room temperature with GLYMO 1 hour；It is small to be incubated for 3
Shi Hou three times with ethanol washing, is then suspended in 10mL acetone until using by nano silicon particles 20 minutes at 4000g.
The concrete operation step of above-mentioned insulin antibody coating silicon nano are as follows: by 1ml silicon nano 10000g from
The heart 5 minutes, vacuum drying was suspended in the 1mLPBS containing 15 μ g anti-insulins, mixes 2 hours at 25 DEG C, 10000g centrifugation 5
Minute, it is incubated for 30 minutes in 1ml200nMTris；It is washed and is suspended in the PBS of 60 μ l three times with PBS, then using preceding 4
DEG C save.
The concrete operation step of insulin in above-mentioned immunity enrichment sample are as follows: test serum sample melts on ice.So
Afterwards at room temperature, 100 μ L samples and Ab-Si nano granule suspension are incubated for 1 hour, are continuously washed with PBS containing the mixture
Ab-Si nano particle 3 times；Finally the silicon nano for being enriched insulin is suspended in 4 μ lPBS, point arrives mass spectrographic target
It is tested and analyzed on plate.
Comparative diagram 1 uses magnetic bead, graphene, nano silicon particles, silver nano-grain and mesoporous silicon as matrix, detects pancreas
The power of island element signal, the result shows that, nano silicon particles and magnetic bead can effectively increase insulin signaling, but ought make shown in Fig. 1
When using magnetic bead as co-substrate, insulin signaling is unstable.
Comparative diagram 3 compares the pancreas islet of different sample type (serum and blood plasma) measurements by detecting 20 clinical samples
Plain concentration.The results show that serum insulin signal is higher than blood plasma.
Comparative diagram 4, by detection 1.25 μ g, 5 μ g, 10 μ g, 15 μ g, 20 μ g, 25 μ g, 30 μ g dosages coated antibody, knot
Fruit shows, when amount of antibody is 10-30 μ g, effective signal can be obtained, and comprehensively considers dosage and signal strength, and 15 μ g are most
Good dosage.
Comparative diagram 5 is better than 2,5- dihydroxy benzenes with the insulin signaling that alpha-cyano -4- hydroxycinnamic acid (CHCA) is matrix
Formic acid (DHB) and erucic acid (SA) are that matrix carries out insulin detection respectively, the results show that effective signal can be obtained, but
The signal of CHCA is most strong, therefore CHCA is the optimum substrate of this insulin measuring table.
It is the methodology validation of detection method below:
1, method validity:
For the validity of verification method, insulin antibody and protein B the SA nano silicon particles being anchored are come as control
Assess detection performance.The nano silicon particles that insulin standards are modified with two kinds mix.Unbonded and non-spy is removed by washing
MALDI analysis is carried out after anisotropic sample.
Comparative diagram 2 can detecte the clear signal (Fig. 2A) of standard insulin after anti-insulin antibody enrichment；It is right
According to cannot identify any signal (Fig. 2 B) in group.This shows that insulin can be used in combination effectively by nano silicon particles immunity enrichment
MALDI-TOFMS detection.
2, detection limit, linear and range:
The quantitative detection limit estimation of comparative diagram 6 and Fig. 7, this method are about 0.1nM, show nano silicon particles-MS measurement tool
There is good sensitivity.
With 0.02%PBST buffer, 5%BSA and simulation serum, (albumin 35mg/mL transfects 2mg/mL, IgG6mg/
ML it) detects, comparative diagram 8, insulin signaling intensity is in good linear relationship, linear regression coeffficient within the scope of 0.1~25nM
It (R2) is 0.9838~0.9901.
3, precision:
Insulin assay precision the results are shown in Table 1.For withinrun precision, the coefficient of variation (CV) is changed to from 1.81%
4.53%.For betweenrun precision, CV value changes to 8.09% from 2.71%, both below 10%.Therefore, silicon nanoparticle
Sub- MS measurement has good reproducibility and precision.
The verifying of 1 precision of table
4, accuracy
Insulin assay accuracy result is shown in Table 2.Between 95.5%~105%, sample volume and measurement are rung the rate of recovery
There are linear relationships between answering.The accuracy of the nano-silicon insulin assay technology of exploitation is acceptable.
2 accuracy validation of table
| Insulin (nM) | Detectable concentration (nM) | Average recovery rate (%) |
| 0 | 0 | 0 |
| 0.2 | 0.191 | 95.5±1.8 |
| 3.0 | 3.153 | 105±3.2 |
5, methods comparison
It collects the clinical serum sample (being to receive insulin therapy) of 40 diabetes while carrying out detection of the invention
The detection of method and chemiluminescence immunoassay.Comparative diagram 9, it is of the invention that result of study was shown wears bright recurrence display
Detection method and chemiluminescence immunoassay have good consistency (y=0.9999x+0.0229), the ratio of two groups of measured values
Relatively show good linear dependence (R2=0.981).
Claims (9)
1. a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, which is characterized in that the method includes pancreas islet
Plain antibody is coated with silicon nano, the insulin in immunity enrichment sample, and washing removes unbonded sample component and non-specific
Property sample, then by be enriched insulin nano silicon particles be added dropwise on MALDI target plate, utilize MALDI-TOF MS carry out pancreas islet
Element detection.
2. according to claim 1 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the silicon nano carries out functional modification by 3- glycidyl ether oxypropyltriethoxysilane, then uses pancreas islet
Plain antibody coating.
3. according to claim 1 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the dosage of the insulin antibody is 10-30 μ g.
4. according to claim 3 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the dosage of the insulin antibody is preferably 15 μ g.
5. according to claim 1 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the sample type is serum or blood plasma.
6. according to claim 5 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the sample type is preferably serum.
7. according to claim 1 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the matrix of the MALDI detection insulin is selected from alpha-cyano -4- hydroxycinnamic acid, 2,5-dihydroxybenzoic acid or erucic acid.
8. according to claim 7 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the matrix of the MALDI detection insulin is preferably alpha-cyano -4- hydroxycinnamic acid.
9. according to claim 1 a kind of based on nano silicon particles-mass spectrum joint-detection insulin method, feature exists
In the washing process uses phosphate buffer.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004077057A1 (en) * | 2003-02-27 | 2004-09-10 | Dakocytomation Denmark A/S | Standard for immunohistochemistry, immunocytochemistry and molecular cytogenetics |
| US20050032116A1 (en) * | 1995-05-23 | 2005-02-10 | Nelson Randall W. | Analysis of insulin-like growth factors from biological fluids by the use of affinity-based mass spectrometric methods |
| CN1873407A (en) * | 2006-06-29 | 2006-12-06 | 复旦大学 | Method for enriching, desalting protein or polypeptide in minute quantities, and carrying out analysis directly |
| CN102662050A (en) * | 2012-05-24 | 2012-09-12 | 东北师范大学 | Immunoassay method based on infrared absorption property of silicon dioxide nanoparticle |
| CN103392219A (en) * | 2010-12-28 | 2013-11-13 | 探索诊断投资公司 | Quantitation of insulin by mass spectrometry |
| CN103454428A (en) * | 2012-06-05 | 2013-12-18 | 许洋 | Novel immunomic mass spectrometry kit for detecting individualized insulin and preparation method thereof |
| CN107548460A (en) * | 2015-03-03 | 2018-01-05 | 奎斯特诊断投资有限公司 | Pass through the horizontal method of mass spectrography quantitative insulin |
-
2018
- 2018-09-25 CN CN201811115773.9A patent/CN109061196A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050032116A1 (en) * | 1995-05-23 | 2005-02-10 | Nelson Randall W. | Analysis of insulin-like growth factors from biological fluids by the use of affinity-based mass spectrometric methods |
| WO2004077057A1 (en) * | 2003-02-27 | 2004-09-10 | Dakocytomation Denmark A/S | Standard for immunohistochemistry, immunocytochemistry and molecular cytogenetics |
| CN1873407A (en) * | 2006-06-29 | 2006-12-06 | 复旦大学 | Method for enriching, desalting protein or polypeptide in minute quantities, and carrying out analysis directly |
| CN103392219A (en) * | 2010-12-28 | 2013-11-13 | 探索诊断投资公司 | Quantitation of insulin by mass spectrometry |
| CN102662050A (en) * | 2012-05-24 | 2012-09-12 | 东北师范大学 | Immunoassay method based on infrared absorption property of silicon dioxide nanoparticle |
| CN103454428A (en) * | 2012-06-05 | 2013-12-18 | 许洋 | Novel immunomic mass spectrometry kit for detecting individualized insulin and preparation method thereof |
| CN107548460A (en) * | 2015-03-03 | 2018-01-05 | 奎斯特诊断投资有限公司 | Pass through the horizontal method of mass spectrography quantitative insulin |
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Application publication date: 20181221 |