CN112834740B - Peptide-like oligomer, preparation method thereof, pharmaceutical composition and microfluidic chip - Google Patents
Peptide-like oligomer, preparation method thereof, pharmaceutical composition and microfluidic chip Download PDFInfo
- Publication number
- CN112834740B CN112834740B CN202011633232.2A CN202011633232A CN112834740B CN 112834740 B CN112834740 B CN 112834740B CN 202011633232 A CN202011633232 A CN 202011633232A CN 112834740 B CN112834740 B CN 112834740B
- Authority
- CN
- China
- Prior art keywords
- oligomer
- chip
- layer
- microfluidic chip
- peptide
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 11
- 230000004048 modification Effects 0.000 claims abstract description 23
- 238000012986 modification Methods 0.000 claims abstract description 23
- 239000002135 nanosheet Substances 0.000 claims abstract description 23
- 239000011521 glass Substances 0.000 claims abstract description 17
- SDAWVOFJSUUKMR-UHFFFAOYSA-N 12-sulfanyldodecanoic acid Chemical compound OC(=O)CCCCCCCCCCCS SDAWVOFJSUUKMR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 108010043958 Peptoids Proteins 0.000 claims description 37
- 239000010410 layer Substances 0.000 claims description 35
- 239000004593 Epoxy Substances 0.000 claims description 10
- 230000004913 activation Effects 0.000 claims description 8
- 239000002346 layers by function Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 229910008051 Si-OH Inorganic materials 0.000 claims description 6
- 229910006358 Si—OH Inorganic materials 0.000 claims description 6
- 238000004140 cleaning Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000000903 blocking effect Effects 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- 229910002808 Si–O–Si Inorganic materials 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000002356 single layer Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 24
- 238000001514 detection method Methods 0.000 abstract description 15
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 10
- 150000003384 small molecules Chemical class 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 abstract description 6
- 230000008878 coupling Effects 0.000 abstract description 5
- 238000010168 coupling process Methods 0.000 abstract description 5
- 238000005859 coupling reaction Methods 0.000 abstract description 5
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 238000001179 sorption measurement Methods 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 238000002715 modification method Methods 0.000 abstract description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 20
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 20
- 239000000523 sample Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 230000027455 binding Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 230000009871 nonspecific binding Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 229910021642 ultra pure water Inorganic materials 0.000 description 6
- 239000012498 ultrapure water Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 5
- 239000002064 nanoplatelet Substances 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- HPFWDCIEYLFOTN-UHFFFAOYSA-N 2-(2-phenylphenyl)ethanamine Chemical compound NCCC1=CC=CC=C1C1=CC=CC=C1 HPFWDCIEYLFOTN-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 101100310856 Drosophila melanogaster spri gene Proteins 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- QVYARBLCAHCSFJ-UHFFFAOYSA-N butane-1,1-diamine Chemical compound CCCC(N)N QVYARBLCAHCSFJ-UHFFFAOYSA-N 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001847 surface plasmon resonance imaging Methods 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- NTASFODDPBHBAM-UHFFFAOYSA-N 1-hydroxyethylazanium;chloride Chemical compound [Cl-].CC([NH3+])O NTASFODDPBHBAM-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- BXQOGTHSKFRGDV-UHFFFAOYSA-N C(CC)[Si](OCC)(OCC)C.[O] Chemical compound C(CC)[Si](OCC)(OCC)C.[O] BXQOGTHSKFRGDV-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108010049175 N-substituted Glycines Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- DBLXOVFQHHSKRC-UHFFFAOYSA-N ethanesulfonic acid;2-piperazin-1-ylethanol Chemical compound CCS(O)(=O)=O.OCCN1CCNCC1 DBLXOVFQHHSKRC-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002052 molecular layer Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
- G01N33/552—Glass or silica
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- 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
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4709—Amyloid plaque core protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention provides a peptide-like oligomer, a preparation method of the peptide-like oligomer, a pharmaceutical composition containing the peptide-like oligomer and a microfluidic chip. The nano-sheet is assembled by the peptide oligomer, and is used for modifying the glass-based microfluidic chip, and the GPTMS and the 12-mercapto-dodecanoic acid are further utilized to form covalent bonds with the nano-sheet of the peptide oligomer through reaction, so that the surface modification of the glass-based microfluidic chip is realized. The method effectively reduces the nonspecific adsorption of the chip surface, provides the coupling groups of the antibody and the small molecules, further improves the detection sensitivity and accuracy of the microfluidic chip, and provides a new choice for in vitro diagnosis. In addition, the modification method is simple, high in efficiency and low in manufacturing cost.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a peptide-like oligomer, a preparation method of the peptide-like oligomer, a pharmaceutical composition containing the peptide-like oligomer and a microfluidic chip.
Background
The term microfluidic chip originally originated from Manz in the 90 th century of 20 and Widmer proposed micro total analysis System (μTAS). The Manz professor successfully applied MEMS technology to analytical chemistry and soon realized high-speed capillary electrophoresis on microchips, and the results were published in journal such as Science, from which rapid attention was paid to and became one of the forefront technological fields in the world today. The Lab-on-a-chip (Lab) and the microfluidic chip (Microfluidic Chip) are different names proposed in this field,as the application of this discipline expands from the original analytical chemistry to multiple research and application fields, and researchers' deep understanding of this discipline, microfluidic chips have become a generic term for this field. Microfluidic is the processing and manipulation of minute quantities (10) within channel systems of tens to hundreds of microns dimensions -9 To 10 -18 Liter) of fluid. A key feature of microfluidic chip technology is manipulation of fluids in microscale channels. It is because the micro-scale structure of the microfluidic chip significantly increases the specific surface area of the fluid, i.e. the ratio of surface area to volume, thereby resulting in a series of special effects related to the surface, such as laminar flow effects, surface tension, capillary effects, rapid thermal conduction effects, diffusion effects, etc., thus bringing about superior performance not possessed by macro-scale laboratory devices.
In the current mainstream detection scheme, the surface of the microfluidic chip is modified by coupling antibodies or molecular probes, and the molecular probes comprise targeting molecules of specific receptor proteins at tumor sites such as antibodies, polypeptides, peptoids and nucleic acid aptamers. However, the coupled functional molecules need to provide sufficient surface-active groups and blocking is also particularly important for chips in order to reduce noise from non-specific adsorption. The surface of the glass-based chip is functionalized through chemical reaction, so that the surface modification of the glass-based chip can be effectively realized, the coupling duration and the effective time of functional molecules are greatly prolonged, the activity of a natural living sample can be ensured, and the method is expected to bring new revelation to in-vitro diagnosis.
Disclosure of Invention
At least one embodiment of the present disclosure provides a peptide-like oligomer comprising: beta-phenylethylamine subunit, 3-aminopropionic acid subunit and ethylenediamine subunit.
For example, in at least one embodiment of the present disclosure, a peptoid oligomer is provided having a structure represented by formula I:
wherein, 10 is more than or equal to n1 is more than or equal to 3, 10 is more than or equal to n2 is more than or equal to 3, n1=n2, and both n1 and n2 are natural numbers.
At least one embodiment of the present disclosure also provides a method for preparing the peptoid oligomer, wherein the method comprises a solid phase synthesis method.
For example, in a preparation method provided in at least one embodiment of the present disclosure, the preparation method includes the steps of:
(1) Attaching a first subunit of said peptoid oligomer to a solid support according to the order of attachment of the subunits of said peptoid oligomer;
(2) Reacting bromoacetic acid with an amino group of a first subunit attached to the solid support under the activation of an activator to form an amide bond;
(3) Reacting the donor of the second subunit of the peptoid oligomer with the product obtained in the step (2), and replacing bromine atoms to complete the connection of the second subunit;
(4) Repeating the connection of the bromoacetic acid and the subsequent subunits until the connection of all subunits is completed;
(5) And (3) cracking the synthesized peptide-like oligomer from the solid phase carrier to obtain the peptide-like oligomer.
At least one embodiment of the present disclosure also provides a pharmaceutical composition comprising: a peptide oligomer of any of the above; pharmaceutically acceptable auxiliary materials.
For example, in the pharmaceutical composition provided in at least one embodiment of the present disclosure, the adjuvant is any one or a combination of at least two of an excipient, a diluent, a carrier, a flavoring agent, a binder, and a filler.
The present disclosure also provides, in at least one embodiment, a use of any of the above pharmaceutical compositions in the preparation of a medicament for detecting or diagnosing a disease associated with alzheimer's disease.
The present disclosure also provides, in at least one embodiment, a use of any of the above pharmaceutical compositions in microfluidic chip modification.
For example, in an application provided by at least one embodiment of the present disclosure, the chip comprises a glass-based microfluidic chip.
The invention also provides a microfluidic chip, which comprises the oligomer nano-sheet layer and a functional layer, wherein the functional layer comprises GPTMS-guided epoxy modification and 12-mercapto-dodecanoic acid-guided closed activation layer modification.
The invention has the following beneficial effects:
the invention provides a peptide-like oligomer, a preparation method of the peptide-like oligomer, a pharmaceutical composition containing the peptide-like oligomer and a microfluidic chip. The nano-sheet is assembled by the peptide oligomer, and is used for modifying the glass-based microfluidic chip, and the GPTMS and the 12-mercapto-dodecanoic acid are further utilized to form covalent bonds with the nano-sheet of the peptide oligomer through reaction, so that the surface modification of the glass-based microfluidic chip is realized. The method effectively reduces the nonspecific adsorption of the chip surface, provides the coupling groups of the antibody and the small molecules, further improves the detection sensitivity and accuracy of the microfluidic chip, and provides a new choice for in vitro diagnosis. In addition, the modification method is simple, high in efficiency and low in manufacturing cost.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following brief description of the drawings of the embodiments will make it apparent that the drawings in the following description relate only to some embodiments of the present invention and are not limiting of the present invention.
FIG. 1 is a schematic diagram showing a method for synthesizing a peptide-like oligomer according to an embodiment of the present invention;
FIG. 2 is a schematic diagram illustrating a two-dimensional nano-sheet material according to an embodiment of the present invention;
FIG. 3 is a fluorescence microscope image of a two-dimensional nanoplatelet layer according to an embodiment of the present invention;
FIG. 4 is a flow chart of a chip surface epoxy modification according to an embodiment of the present invention;
FIG. 5 is a schematic diagram of a glass-based chip surface modification and functional layer structure according to an embodiment of the present invention;
FIG. 6 is a graph showing the result of reduction of nonspecific binding signals of a chip surface modification according to an embodiment of the present invention; the method comprises the steps of,
FIG. 7 is a graph showing the results of detection affinity for the Alzheimer's disease biomarker Abeta 42 provided in one embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. All other embodiments, which can be made by a person skilled in the art without creative efforts, based on the described embodiments of the present invention fall within the protection scope of the present invention.
Unless defined otherwise, technical or scientific terms used in this disclosure should be given the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. The terms "first," "second," and the like, as used in this disclosure, do not denote any order, quantity, or importance, but rather are used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that elements preceding the word are meant to encompass the elements listed after the word as well as equivalents thereof without excluding other elements.
The experimental methods used in the following examples are conventional methods unless otherwise specified. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
The SPRi instrument in the following examples is Plexera Kx5V2, plexera Bioscience LLC, USA, which is mainly equipped with 660nm led light source, CCD image collector and sensor chip with microfluidic channel, which displays the change of reflected light intensity with time at each monitoring point and records as SPR curve.
"nM" herein refers to "nmol/L" and "mM" refers to "mmol/L" unless specifically stated otherwise.
The peptoid molecule has the characteristics of low immunogenicity, good tissue permeability, high stability, easy modification, low manufacturing cost and the like. However, in the application of molecular probes, the binding capacity of the peptoid small molecules and the biosensor is not strong, so that the peptoid small molecules cannot be used as probe molecules; the antibody has the characteristic of tightly combining with the biosensor, but the arrangement of the antibody molecules is disordered, and the arrangement direction of the antibody molecules on the surface of the sensor is randomly difficult to control, so that the specificity of the antibody is low, and the cost of the antibody is high. The inventor of the present disclosure found that an oligomer formed from a peptoid small molecule and an antibody can well bind the peptoid small molecule and the antibody, i.e., the peptoid oligomer has the characteristic that the antibody can be tightly bound with a biosensor, and the peptoid small molecule can be orderly formed on the surface of the sensor. In addition, the molecular probe formed by the oligomer has strong affinity with a target, and the oligomer cannot be subjected to enzymolysis, so that the activity of a natural living sample can be ensured.
Compared with polypeptide, polypeptide takes alpha amino acid as structural unit, and N-substituted glycine as structural unit. The peptoid compound has good biological activity and pharmacological properties, can effectively detect or inhibit deterioration in vivo experiments, and has good cell membrane penetrability. Currently, the mature peptoid synthesis technology is the "subunit synthesis" technology.
At least one embodiment of the present disclosure further provides a peptide-like oligomer having a molecular structural formula:
wherein, 10 is more than or equal to n1 is more than or equal to 3, 10 is more than or equal to n2 is more than or equal to 3, n1=n2, and both n1 and n2 are natural numbers.
For example, the oligomer includes: beta-phenylethylamine subunit, 3-aminopropionic acid subunit and ethylenediamine subunit.
For example, the structural formula of each subunit is as follows:
for example, in an oligomer provided in at least one embodiment of the present disclosure, the oligomer comprises subunits arranged in the following order: [ beta-phenethylamine subunit-3-aminopropionic acid subunit]n 2 -probe- [ beta-phenylethylamine subunit-ethylenediamine subunit]n 1 。
At least one embodiment of the present disclosure also provides a method of preparing an oligomer comprising synthesizing subunits by solid phase synthesis.
For example, fig. 1 is a flowchart of a method for preparing a peptoid oligomer according to one embodiment of the disclosure, the method comprising the steps of:
step S1: ligating a first subunit of the oligomer to the solid support according to the order of ligation of the subunits of the oligomer;
step S2: reacting bromoacetic acid with an amino group of a first subunit attached to a solid support under activation of an activator to form an amide bond;
step S3: reacting the donor of the second subunit of the peptoid oligomer with the product obtained in the step S2 to replace bromine atoms and complete the connection of the second subunit;
step S4: repeating the connection of bromoacetic acid and the subsequent subunits until the connection of all subunits is completed;
step S5: the synthesized oligomer is cleaved from the solid phase carrier to obtain the peptide oligomer.
For example, the oligomer comprises a side chain formed by the left side peptide-like compound and the right side peptide-like compound, and further comprises various probes embedded in the peptide-like compound for detection, wherein the left side chain comprises amino groups, the right side chain comprises carboxyl groups, the side chain helps the oligomer to form a two-dimensional lamellar structure, so that the middle probes are exposed on the surface of a sensor for detecting various targets, and the side chain can further enable the oligomer to be arranged more orderly.
For example, in the oligomer, n1=n2=3, n1=n2=4, n1=n2=6, n1=n2=8, or n1=n2=10.
It should be noted that when n1 and n2 are smaller than 3, there is a problem that the chain length is too short to be assembled; when n1 and n2 are greater than 10, the chains formed are too long, and the density of the intermediate inserted peptoid compound of the oligomer is too low, a decrease in affinity occurs, and thus specific binding to the target molecule cannot be achieved.
Example one
The molecular structure is as follows:
the preparation method of the oligomer with n1=n2=4, n1=n2=6 or n1=n2=8 specifically comprises the following steps:
(1) Rink amide AM resin (initial resin for polypeptide synthesis, substitution level 0.3 mmol/g) was swelled and deprotected with piperidine, and beta-phenethylamine was equimolar mixed with 1-hydroxybenzotriazole and coupled under activation of N-methylmorpholine.
(2) 10mL of bromoacetic acid with the concentration of 2mol/L and 10mL of N, N' -Diisopropylcarbodiimide (DIC) with the concentration of 3.2mol/L are added into Rink amide AM resin, and the mixture is reacted for 30min at 38 ℃ to acylat the amino groups at the tail ends of the resin;
(3) Adding 2mol/L primary amine, reacting for 90min at 37 ℃, and replacing bromine atoms through nucleophilic substitution reaction to complete synthesis of one subunit;
(4) Repeating the steps (2) and (3) until synthesis of the rest units is completed;
(5) After the synthesis was completed, the side chain protecting groups were removed and the oligomer was cleaved from the resin with 95% trifluoroacetic acid, 2.5% ultrapure water and 2.5% triisopropylsilane, respectively, by mass percent, for further use.
In the process of forming the oligomer with the structure, subunit feeding sequences are as follows:
beta-phenethylamine, 3-aminopropionic acid, beta-phenethylamine, 3-aminopropionic acid; beta-phenethylamine, 3-aminopropionic acid, beta-phenethylamine, 3-aminopropionic acid; beta-phenethylamine, 3-aminopropionic acid, beta-phenethylamine, 3-aminopropionic acid; beta-phenethylamine, 3-aminopropionic acid, beta-phenethylamine, 3-aminopropionic acid; acetic acid amine, butanediamine, alpha-methylbenzylamine, butanediamine, isobutylamine, piperonyl amine, butanediamine; beta-phenethylamine, ethylenediamine, biphenylethylamine, ethylenediamine; beta-phenethylamine, ethylenediamine, biphenylethylamine, ethylenediamine; beta-phenethylamine, ethylenediamine, biphenylethylamine, ethylenediamine; beta-phenethylamine, ethylenediamine, biphenylethylamine, ethylenediamine.
For example, the oligomer may be dissolved to a material in an amount ratio of dimethyl sulfoxide: water=2:1 dimethyl sulfoxide (DMSO) and water (H 2 O) to a concentration of 2mM.
The preparation method of the two-dimensional nano sheet material provided by the embodiment of the invention comprises the following steps:
(1) The peptoid oligomer is distributed at a gas-liquid interface through amphipathy;
(2) Applying lateral pressure to the molecular chains of the peptoid oligomer to form a compact monomolecular layer;
(3) By further increasing the lateral pressure applied to the critical point, the monolayer collapses into the aqueous solution to form a bilayer.
For example, fig. 2 is a schematic diagram of a two-dimensional oligomer forming process according to an embodiment of the present disclosure, and as shown in fig. 2, the two-dimensional oligomer forming process includes: placing an oligomer provided by an embodiment of the present disclosure in a langmuir tank, the oligomer comprising a hydrophilic end and a hydrophobic end, the oligomer being arranged disordered at an interface of a gas and a liquid in the absence of an external force; then applying an external force to the unordered oligomers, wherein the oligomers are orderly arranged at a gas-liquid interface; further, an external force is applied to the ordered arrangement of oligomers, which are extruded under the gas-liquid interface, under which hydrophilic ends are exposed to the outside and hydrophobic ends are formed to the inside, thereby forming a two-dimensional structure.
The formation process of the oligomer nano-sheet layer is as follows: the oligomer obtained in example one above, at a concentration of 2mM, was dissolved in a solution containing 10mM 4-hydroxyethyl piperazine ethanesulfonic acid, 100mM sodium chloride, ph=8.0, diluted to a sheet forming buffer to a final concentration of 1-100 μm, for example, 20 μm, and then manually shaken: the peptoid solution is stably stored for 22 hours at room temperature, then is manually and gently shaken for 30 seconds, is further stabilized for 1 minute, and the shaking-stabilizing process is repeated for 5 times; or a machine shaking method: the peptoid solution was slowly spun (0.6 rpm) in the tube from horizontal to vertical, once every 450 seconds; the resulting peptoid nanoplatelet solution was added to nile red to a final concentration of 1 μm, and the solution was placed on 1% agar and observed using a fluorescence microscope (ver. A1, carl Zeiss Far East, germany) as shown in fig. 3, and a distinct nanoplatelet structure was observed.
The microfluidic chip is used for biomedical detection and diagnosis, except that the nonspecific binding is one of the most main factors causing false positive or false negative, so that the shielding of nonspecific adsorption has great scientific and commercial significance. Although the blocking reagent such as BSA, ethanolamine and the like in the traditional sense can reduce partial non-specific binding, the effect is not ideal, and particularly for targets with extremely low content, the requirements on sensitivity and specificity are more strict, so that the detection sensitivity and specificity are improved by a chip surface modification technology, and the method has extremely important scientific significance.
The embodiment of the disclosure provides a method for finishing the surface modification of a glass chip by combining the peptide-like nano-sheet layer through covalent connection, wherein 3-glycidol ether oxygen propyl methyl diethoxy silane (GPTMS) and 12-mercapto dodecanoic acid form a complete functional molecular layer through three-step reaction.
Wherein, GPTMS formula is:
the structural formula of the 12-mercapto dodecanoic acid is as follows:
as shown in fig. 4, the main steps of epoxy modification of the surface of the glass chip of the present invention are as follows:
(1) In an aqueous solution system, the methyl of GPTMS and water molecules are subjected to hydrolysis reaction to generate Si-OH;
(2) The GPTMS molecule containing Si-OH and Si-OH on the surface of the glass chip undergo condensation reaction to form Si-O-Si bond.
The glass chip modified by the epoxy is modified by a dense monomolecular layer by using 12-mercapto dodecanoic acid, the surface of the chip is effectively sealed, and-COOH required by the coupling of the peptide-like nanosheet is provided, and the specific steps are as follows:
(1) Placing the epoxy modified chip in pure water for full cleaning;
(2) Placing the chip in 1M 12-mercaptododecanoic acid water solution for full reaction for 24 hours to form a dense monomolecular layer;
(3) The chip was depth-washed with 10 XPBS, 1 XPBS, and ultra-pure water, respectively, for use.
The functional layer modification is carried out by utilizing the nano-sheet layer assembled by the peptide-like oligomer with the probe to form a complete chip structure, as shown in fig. 5, the specific steps are as follows:
(1) Sequentially performing deep cleaning on the epoxy modified and sealed chip by using 10 XPBS, 1 XPBS and ultrapure water;
(2) EDC/NHS is added in the ratio of 1:1 to carry out carboxyl activation;
(3) And (5) spotting the peptoid nanosheets, and washing the chip after incubation overnight.
The chip structure is shown in fig. 5, and is sequentially provided with an oligomer nanosheet layer, a GPTMS and 12-mercaptododecanoic acid modified functional molecule layer, a structural layer, a PVX layer, a Gate (integrated circuit layout) layer and a glass substrate layer from top to bottom. Wherein the structural layer, the PVX layer, the Gate layer and the glass substrate layer are the basic structure of the biochip.
The oligomer provided by the embodiment of the disclosure has simple synthesis process and strong binding capacity with Abeta 42, and has extremely high affinity modification on the surface of the glass-based chip, so that the capture of Abeta 42 can be effectively realized, and the blood diagnosis of Alzheimer disease can be further realized.
For example, FIG. 6 is a graph showing the results of the non-specific binding signals of the chips of the present invention and the comparative example over time, wherein bio-chip is the chip containing the peptoid oligomer and the modified functional molecule layer provided in the above-described examples, and control is the chip containing the peptoid oligomer without GPTMS and 12-mercaptododecanoic acid modification. The modified chip can be seen to greatly reduce the nonspecific binding signal and improve the specificity and the signal-to-noise ratio. The test steps for reducing the nonspecific binding signal after the chip is modified by using the enzyme-labeled instrument are as follows:
(1) Sequentially performing deep cleaning on the modified chip by using 10 XPBS, 1 XPBS and ultrapure water;
(2) EDC/NHS is added in the ratio of 1:1 to carry out carboxyl activation;
(3) Performing peptide-like nanosheet spotting, sufficiently incubating overnight, cleaning the chip, and using the chip directly coated with the probe and the chip blocked by 2.5% BSA and 5% ethanolamine as a control;
(4) The PBS solution of FITC-HSA is prepared, the test chip and the control chip of the step (3) are introduced at the flow rate of 2 mu L/s, and fluorescent signals are collected every minute.
For example, the procedure for testing the binding capacity between oligomer and aβ42 using surface plasmon resonance imaging techniques is as follows:
(1) Dissolving the oligomer-assembled nanoplatelets to ddH 2 The concentration of the oligomer in O is 1-1000 mu M;
(2) The oligomer solution is spotted on the surface of a chip which is modified by epoxy and is sealed, each sample is repeated for 3 spots, after the sample is placed for 12 hours at the temperature of 4 ℃, the chip is cleaned by 10 XPBS, 1 XPBS and ultrapure water in sequence, then the chip is sealed by 1M aminoethanol hydrochloride for 30 minutes, then the chip is cleaned by ultrapure water for 5 times, and finally the chip is dried by nitrogen;
(3) Mounting a chip on an SPRi instrument, measuring an SPRi angle and adjusting the SPRi angle to an optimal optical position, selecting related detection points including sample points and blank points in a detection area, and setting an experimental flow rate to be 3 mu L/s;
(4) PBS was selected as buffer solution and passed through the flow cell until the baseline was stable, and then sequentially passed through concentrations of 5.68nM, 11.4nM, 22.8nM, 45.6nM and 91.2nM, the binding time was 300 seconds, the dissociation time was 300 seconds, and phosphoric acid was passed through each concentration to regenerate.
For example, fig. 7 is a graph of the results of surface plasmon resonance detection of oligomers bound to aβ42 at concentrations of 5.68nM, 11.4nM, 22.8nM, 45.6nM and 91.2nM, respectively, in example one of the present disclosure, where a.u. represents the binding signal of the mobile phase after passing through the array minus the baseline signal of the initial PBS buffer, the curve is the test results for PlexArray HT, the fitted line is a biaevaluation 4.1 fit, 91.2nM detection line, 45.6nM detection line, 22.8nM detection line, 11.4nM detection line and 5.68nM detection line, in order from top to bottom. The a.u. is a unit for reflecting the strength of the binding signal in surface plasmon resonance imaging, and is a dimensionless unit. Fitted, the equilibrium dissociation constant KD is 1.57×10 -10 Molar/liter, which indicates that the peptide-like nanosheet with probe has a fairly high affinity level for aβ42.
For example, the oligomer is a two-dimensional nanoplatelet material, which allows the oligomer to be coupled to the sensor and the peptoid oligomer with affinity to be displayed on the surface of the sensor.
Two-dimensional peptoid nanomaterials play an increasingly important role in biology and electronics, such as sensing, growth and filtration of templates, and testing of proteins for their molecular recognition and catalytic ability as mimics of proteins. The Langmuir trough experimental device reveals that the formation of the peptoid nanosheet layer is an unusual thermodynamic equilibrium process of self-assembly of peptoid molecules and conversion of external mechanical energy into chemical energy of the peptoid molecules.
For example, the pharmaceutical composition further comprises: the peptoid oligomer of any one of the foregoing claims; pharmaceutically acceptable auxiliary materials.
For example, the adjuvant includes any one or a combination of at least two of an excipient, a diluent, a carrier, a flavoring agent, a binder, and a filler.
For example, the excipient may be, for example, an emulsion or oily suspension, or a polyalkylene glycol such as polypropylene glycol.
The embodiment of the invention provides a peptide-like oligomer, a preparation method of the peptide-like oligomer, a pharmaceutical composition containing the peptide-like oligomer and a microfluidic chip. Has at least one of the following beneficial effects:
(1) In the peptoid nanosheet layer provided in at least one embodiment of the present disclosure, the peptoid nanosheet layer with the probe has a strong binding capacity with the target molecule, and the equilibrium dissociation constant KD in the binding kinetic constant of the nanosheet layer and the target molecule obtained by the surface plasmon resonance technology is 10 -10 On the order of moles/liter;
(2) In the chip modification technology provided by at least one embodiment of the present disclosure, chip epoxidation and carboxylation can be effectively performed;
(3) In the chip modification technology provided by at least one embodiment of the present disclosure, a chip based on the modification technology can effectively reduce non-specific binding to substances other than a target;
(4) The synthesis method of the peptoid oligomer provided by at least one embodiment of the present disclosure is simple, the preparation efficiency is high, and the manufacturing cost is low;
(5) The assembling method of the peptoid nano-sheet layer provided by at least one embodiment of the present disclosure is simple, the preparation efficiency is high, and the manufacturing cost is low.
The following points need to be described:
(1) The drawings of the embodiments of the present invention relate only to the structures related to the embodiments of the present invention, and other structures may refer to the general designs.
(2) In the drawings for describing embodiments of the present invention, the thickness of layers or regions is exaggerated or reduced for clarity, i.e., the drawings are not drawn to actual scale.
(3) The embodiments of the invention and the features of the embodiments can be combined with each other to give new embodiments without conflict.
The above description is only specific embodiments of the present invention, but the scope of the present invention should not be limited thereto, and the scope of the present invention should be determined by the claims.
Claims (3)
1. A microfluidic chip is characterized in that the microfluidic chip comprises a nano sheet layer and a functional layer,
the nano-sheet layer contains a peptoid oligomer shown in a formula I,
the functional layer comprises GPTMS-guided epoxy modification and 12-mercapto dodecanoic acid-guided closed activation layer modification;
i type
Wherein, n1 is more than or equal to 10 and more than or equal to 3, n2 is more than or equal to 10 and more than or equal to 3, n1=n2, and n1 and n2 are both natural numbers;
the main steps of epoxy modification are as follows:
(1) In an aqueous solution system, the methyl of GPTMS and water molecules are subjected to hydrolysis reaction to generate Si-OH;
(2) The GPTMS molecule containing Si-OH and Si-OH on the surface of the glass chip undergo condensation reaction to form Si-O-Si bond;
the modification of the blocking activation layer comprises the following steps:
(1) Placing the epoxy modified chip in pure water for full cleaning;
(2) The chip was placed in a 1m aqueous solution of 12-mercaptododecanoic acid to react well to form a dense monolayer.
2. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises a nano-sheet layer, a functional layer, a structural layer, a PVX layer, a Gate layer and a glass substrate layer from top to bottom.
3. The microfluidic chip according to claim 1, wherein in formula i, n1=n2=3, n1=n2=4, n1=n2=6, n1=n2=8, or n1=n2=10.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011633232.2A CN112834740B (en) | 2020-12-31 | 2020-12-31 | Peptide-like oligomer, preparation method thereof, pharmaceutical composition and microfluidic chip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011633232.2A CN112834740B (en) | 2020-12-31 | 2020-12-31 | Peptide-like oligomer, preparation method thereof, pharmaceutical composition and microfluidic chip |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112834740A CN112834740A (en) | 2021-05-25 |
| CN112834740B true CN112834740B (en) | 2023-10-24 |
Family
ID=75925901
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011633232.2A Active CN112834740B (en) | 2020-12-31 | 2020-12-31 | Peptide-like oligomer, preparation method thereof, pharmaceutical composition and microfluidic chip |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112834740B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113275049A (en) * | 2021-05-18 | 2021-08-20 | 京东方科技集团股份有限公司 | Preparation method of biochip, biochip and detection device |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101363870A (en) * | 2008-09-18 | 2009-02-11 | 清华大学 | Bio-sensing chip and method for making same |
| CN101745495A (en) * | 2008-12-12 | 2010-06-23 | 中国科学院理化技术研究所 | Method for inhibiting non-specific adsorption on solid material surface |
| CN105753940A (en) * | 2016-02-05 | 2016-07-13 | 国家纳米科学中心 | Peptoid inhibitor as well as preparation method and application thereof |
| CN106866794A (en) * | 2017-02-15 | 2017-06-20 | 国家纳米科学中心 | One species peptide and its preparation method and application |
| CN110818777A (en) * | 2018-08-10 | 2020-02-21 | 国家纳米科学中心 | Peptide-like nanosheet layer, and preparation method and application thereof |
| CN110981936A (en) * | 2018-09-28 | 2020-04-10 | 北京京东方技术开发有限公司 | Peptoid compound, preparation method thereof, oligomer, pharmaceutical composition and kit |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4264002B2 (en) * | 2001-07-17 | 2009-05-13 | バイオ−ラド ラボラトリーズ インコーポレイテッド | Latex-based adsorption chip |
-
2020
- 2020-12-31 CN CN202011633232.2A patent/CN112834740B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101363870A (en) * | 2008-09-18 | 2009-02-11 | 清华大学 | Bio-sensing chip and method for making same |
| CN101745495A (en) * | 2008-12-12 | 2010-06-23 | 中国科学院理化技术研究所 | Method for inhibiting non-specific adsorption on solid material surface |
| CN105753940A (en) * | 2016-02-05 | 2016-07-13 | 国家纳米科学中心 | Peptoid inhibitor as well as preparation method and application thereof |
| CN106866794A (en) * | 2017-02-15 | 2017-06-20 | 国家纳米科学中心 | One species peptide and its preparation method and application |
| CN110818777A (en) * | 2018-08-10 | 2020-02-21 | 国家纳米科学中心 | Peptide-like nanosheet layer, and preparation method and application thereof |
| CN110981936A (en) * | 2018-09-28 | 2020-04-10 | 北京京东方技术开发有限公司 | Peptoid compound, preparation method thereof, oligomer, pharmaceutical composition and kit |
Non-Patent Citations (2)
| Title |
|---|
| Antibody-Mimetic Peptoid Nanosheet for Label-Free Serum-Based Diagnosis of Alzheimer’s Disease;Ling Zhu 等;《Adv. Mater.》;20170612;第1-7页 * |
| Structure-Rheology Relationship in Nanosheet-Forming Peptoid Monolayers;Ellen J.Robertson等;《Langmuir》;20161231;第A-M页，图1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112834740A (en) | 2021-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2281424T3 (en) | MICROMATRICES TO CARRY OUT PROTEOMIC ANALYSIS. | |
| EP2541248B1 (en) | Preparation method of antigen-immobilized immunofluorescence slide, and immunofluorescence slide prepared thereby | |
| WO2003005013A1 (en) | Filtration-based microarray chip | |
| Ha et al. | Oriented immobilization of antibodies with GST-fused multiple Fc-specific B-domains on a gold surface | |
| JP5538726B2 (en) | Sol composition for a sol-gel biochip for immobilizing a probe to a substrate that has not been surface-treated and a screening method thereof | |
| WO2017196969A1 (en) | Multivalent glycan microarray platform | |
| CN112834740B (en) | Peptide-like oligomer, preparation method thereof, pharmaceutical composition and microfluidic chip | |
| CN110981936B (en) | Peptoid compound, preparation method thereof, oligomer, pharmaceutical composition and kit | |
| Drozd et al. | Recent advancements in receptor layer engineering for applications in SPR-based immunodiagnostics | |
| De Girolamo et al. | Immobilization of aptamers on substrates | |
| CN102565415B (en) | Protein in situ expression chip, and constructing method and application thereof | |
| CN107486270B (en) | Preparation method of microarray chip based on ball-brush double-layer nanostructure substrate | |
| ES2797391T3 (en) | Surface functionalization procedure for analyte detection | |
| KR101489868B1 (en) | Method for modifying surface of solid phase for introducing biomolecules to the surface, nano-sized particle and sheet having surface modified thereby | |
| CN110325858A (en) | Biological substance process for fixation and its utilization | |
| ES2296297T3 (en) | MOLECULAR ORIENTATION OF MACROMOLECULES THROUGH THE ACTION OF A MENISCO ON HIGHLY SPECIFIC SURFACES. | |
| US20090221449A1 (en) | Presentation of Recognition Motifs by a Multivalent Matrix Grafted Onto a Solid Support | |
| KR101195253B1 (en) | Preparation method of antigen-immobilized immuno- fluorescence slide and the immuno-fluoroscence slide made by the method | |
| KR101317321B1 (en) | Molecular imprinting chip for serum amyloid p component protein | |
| JP2005221423A (en) | Substrate for manufacturing surface plasmon resonance antibody array sensor, and manufacturing method therefor | |
| CN113227117B (en) | Peptoid compound and detection chip with peptoid compound coupled to surface | |
| US20220154273A1 (en) | Incorporation and imaging mixes | |
| WO2008030071A1 (en) | Detecting method of dna hybridization using scattering | |
| US20130109591A1 (en) | Planar support having an ultraflat surface and a device for detecting antigens comprising said planar support | |
| Popot et al. | Amphipol-Mediated Immobilization of Membrane Proteins and Its Applications |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |