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CN101907573B - High-sensitivity integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip - Google Patents

High-sensitivity integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip Download PDF

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CN101907573B
CN101907573B CN2010102554333A CN201010255433A CN101907573B CN 101907573 B CN101907573 B CN 101907573B CN 2010102554333 A CN2010102554333 A CN 2010102554333A CN 201010255433 A CN201010255433 A CN 201010255433A CN 101907573 B CN101907573 B CN 101907573B
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rolling circle
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CN101907573A (en
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陈国平
郭红斌
秦亚杰
洪志良
刘冉
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Fudan University
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Abstract

本发明属于生物医学检测技术领域，具体为一种高灵敏度集成CMOS光学生物芯片。该芯片含有基于CMOS工艺的光电探测器,光电探测器包括光电转换电路、光电流读出电路和模数转换电路；目标分子固定于光电探测器表面，分子探针结合到目标分子上；所述分子探针链接有一段引物链，经过滚环扩增后分子探针上连接有由数百个相同重复结构单位组成的超长链，每一个重复结构单位通过核苷酸互补配对作用，再连接上具有过氧化物酶催化化学发光功能的DNAzyme结构，加入底物后发生化学发光，光信号由光电探测器转换为电信号。整个芯片系统基于CMOS工艺，没有光学元件，背景噪声低，系统结构简单，成本降低；采用滚环扩增技术和特定DNAzyme结构，极大提高了检测灵敏度。

Figure 201010255433

The invention belongs to the technical field of biomedical detection, in particular to a high-sensitivity integrated CMOS optical biochip. The chip contains a photodetector based on CMOS technology, and the photodetector includes a photoelectric conversion circuit, a photocurrent readout circuit and an analog-to-digital conversion circuit; the target molecule is fixed on the surface of the photodetector, and the molecular probe is bound to the target molecule; Molecular probe links have a primer chain. After rolling circle amplification, the molecular probe is connected to an ultra-long chain composed of hundreds of identical repeating structural units. Each repeating structural unit is connected by nucleotide complementary pairing. The DNAzyme structure with peroxidase-catalyzed chemiluminescence function, chemiluminescence occurs after adding the substrate, and the light signal is converted into an electrical signal by the photodetector. The entire chip system is based on CMOS technology, without optical components, low background noise, simple system structure, and low cost; using rolling circle amplification technology and specific DNAzyme structure, the detection sensitivity is greatly improved.

Figure 201010255433

Description

A kind of highly sensitive integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip
Technical field
The invention belongs to biomedical detection technique field, be specifically related to a kind of integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip, be used for highly sensitive detections such as antigen-antibody, nucleic acid molecules based on the large scale integrated circuit technology.
Background technology
Biochip technology is 20th a century microelectric techniques and new technique of biotechnology mixing together; It turns to principal character with array; In conjunction with meticulous mechanical scanning, sensitive optical detection, single-minded software processes and friendly visualization interface; Be used widely at biomedical sector, the era gene in the back carries out function information for the magnanimity genetic fragment and locatees a kind of very important instrument that provides especially.
Biochip roughly can be divided into electrical detection and two kinds of methods of optical detection according to detection method; Wherein optical detecting method uses the most general because of factor such as highly sensitive, that antijamming capability is strong, mark is convenient; And have commercial product successfully to introduce to the market, in clinical medicine, biomedical research, be used widely.In the optical type biochip system; Apparatus structure is very complicated; Light path design requires than higher; Such as the stability laser instrument all very high with monochromaticity (laser instruments of some biochip even several kinds of different excitation wavelengths of needs), optical filter, spectroscope, diaphragm, condenser lens etc. are arranged, special-purpose mechanical scanning system also is equipped with, realize opto-electronic conversion by highly sensitive photodetector (like photomultiplier).Therefore equipment price is expensive, and testing cost is also very high, and architecture is huge.Therefore how to develop a kind of low price, flexible and convenient to use, the focus that can become present research to the biochip of application-specific object,, low-power consumption portable for developing, biochip simple in structure also have important value very much.The lsi technology technology provides possibility for mass large-scale production IC-components, on the one hand through mass production, reduces the cost of single electron device greatly; On the other hand, all devices all are under same environmental conditions, to accomplish on the chip, can guarantee as far as possible that the performance parameter of device is consistent.
Summary of the invention
The object of the present invention is to provide a kind of portable, low-power consumption, integrated CMOS biochip simple in structure.
The highly sensitive integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip that the present invention proposes comprises:
(1) a kind of CMOS photodetector based on the preparation of large scale integrated circuit technology;
(2) be fixed in the target molecule of CMOS photodetector surfaces;
(3) can with the interactional detection molecules of target molecule generation specificity, realize target molecule is discerned; Said detection molecules contains a primer, causes the product that duplicates of one or more rolling circle amplifications, duplicates product and still is connected the detection molecules surface;
(4) G-quadruplex-hemin composite structure is fixed on through linking arm on the product of rolling circle amplification;
(5) under G-quadruplex-hemin catalysis, luminol and oxydol generation chemiluminescence produce light signal, carry out opto-electronic conversion by the CMOS photodetector, realize the evaluation of one or more target molecule.
Among the present invention, said CMOS photodetector is integrated photoelectric switching circuit module, photocurrent sensing circuit module and analog to digital conversion circuit module; Wherein, photodiode, the avalanche photodide of CMOS technology or the phototriode of CMOS technology of the described photoelectric switching circuit module CMOS technology that is array; Described photocurrent sensing circuit module is resistive transimpedance amplifier or capacitive character transimpedance amplifier, and it converts photocurrent into voltage signal; Described analog to digital conversion circuit module is to convert the voltage signal that the current read circuit module produces into digital signal, is convenient to follow-up further digitized processing.
Among the present invention, said target molecule is nucleic acid (DNA or RNA), oligonucleotide chain or polynucleotide chain.Corresponding detection molecules is nucleic acid, oligonucleotide chain or polynucleotide chain, this detection molecules some can with described target molecule complementary pairing, another part produces one or more rolling circle amplification products as primer.
Among the present invention, said target molecule also can be antigen-antibody, polypeptide or protein.Corresponding detection molecules is antibody antigen or other parts, and detection molecules should can specificity interact and combine with described target molecule, and this detection molecules is modified with one section primer, to produce one or more rolling circle amplification products.
Among the present invention, said rolling circle amplification is that linear amplification duplicates product.
Among the present invention; Said G-quadruplex-hemin is the quadruplex structure that forms in many guanines (G) nucleotide chain molecule by containing; Have a peroxidase catalysis structure with hemin (protohemin) is compounded to form, this composite structure couples together through linking arm and rolling circle amplification product.
Among the present invention, said linking arm is an oligonucleotide chain, is linked in the product that described rolling circle amplification duplicates through the base complementrity matching method.
The biochip test method ultimate principle that the present invention relates to is following:
Adopt the lsi technology technical design to go out photodetection chip layout, then flow and carry out optical performance test based on CMOS technology.This chip comprises photoelectric switching circuit module, photocurrent sensing circuit module and analog to digital conversion circuit module.The photoelectric switching circuit module converts light signal into photocurrent; Photocurrent sensing circuit module converts photocurrent into voltage signal; Analog-to-digital conversion module converts the magnitude of voltage of simulation into digital voltage signal, so that the follow-up analyzing and testing of carrying out.
The photodetection chip surface covers goes up SiO 2, can protect chip on the one hand, can fix target molecule on the other hand.The photodetection chip surface is through the fixing target molecule of going up of modes such as chemical modification, physisorption, self assembly.Detection molecules interacts through intermolecular specificity and is attached to target molecule, thereby realizes the identification to target molecule.Detection molecules is connected with the section of DNA chain, and this chain can cause the amplification of DNA isothermal rolling-circle as primer.
Rolling circle amplification is a kind of isothermal duplication process; With the section of DNA chain that connects on the detection molecules is primer; With the cyclic DNA chain is the amplification masterplate, under the archaeal dna polymerase effect, dNTP is carried out the prolongation that polyreaction reaches the DNA chain; Thereby on detection molecules, produce the long-chain of forming by hundreds of the repetitive structure units that connect repeatedly, each repetitive structure unit all with cyclic DNA chain complementary pairing.After the rolling circle amplification process, connecting a length dna strand on the detection molecules, and detection molecules still is fixed in the photodetection chip surface.
G-quadruplex is the nucleotide chain that contains specific poly guanine (G), and the poly guanine is mutual chelating in the space, forms special space structure.After adding hemin (protohemin), hemin and G-quadruplex form G-quadruplex-hemin composite structure (being DNAzyme), and this structure has the peroxidase catalysis, catalysis H 2O 2With luminol chemiluminescence takes place, photodetection core device detects this light signal.DNAzyme is connected with the rolling circle amplification product through linking arm.Linking arm is one section oligonucleotide chain, with repetitive structure unit's complementary pairing of rolling circle amplification product, thereby DNAzyme is connected on the long-chain of rolling circle amplification generation.
The present invention has significant technical progress and use value, and its beneficial effect embodies as follows:
Adopt the lsi technology technology to make photodetector, large-scale production in batches reduces the price of single biochip greatly, even can be made into disposable biochip; In the testing circuit of traditional biochip; Photodetector module, photocurrent read module and analog-to-digital conversion module all is made up of discrete device; Increase system noise, reduced the sensitivity that detects, and photoelectric switching circuit module of the present invention, photocurrent sensing circuit module and analog to digital conversion circuit module are integrated in the chip; Increase the integrated level of functional module, reduced noise greatly;
The so-called biochip of the present invention does not contain any optical element (like condenser lens, optical filter, grating, optics enhanced system and light source etc.), and system architecture is compact;
The chemiluminescence method of the DNAzyme catalysis that the present invention adopts; Need not laser instrument etc. as light source; Reduce ground unrest greatly, improve detection sensitivity, simultaneously owing to combine the rolling circle amplification technology; Detection molecules is passed through to combine last hundreds of DNAzyme molecules behind the isothermal amplification technique; Be equivalent to connect on the detection molecules hundreds of horseradish peroxidase molecules, and the ELISA of traditional superoxide enzymatic is technological, the ratio of detection molecules (like antigen, antibody) and peroxidase is basically at 1:1～1:3; Chemiluminescence intensity is linear with the concentration of enzyme molecule to a certain extent, therefore combines greatly to have improved chemiluminescence detection sensitivity after the rolling circle amplification technology.
Description of drawings
Highly sensitive integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip outside drawing of Fig. 1 and structural drawing.
The highly sensitive integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip structure function of Fig. 2 figure.
The highly sensitive integrated CMOS (Complementary Metal Oxide Semiconductor) optical biological chip of Fig. 3 detects schematic diagram.Wherein, (1) target molecule is fixed to the CMOS photodetector surfaces; (2) detection molecules (being connected with primer) combines with the target molecule specificity; (3) the DNA chain elongation of detection molecules behind the rolling circle amplification; (4) DNA chain and the G-quadruplex-hemin molecule after the prolongation combines; (5) add luminol and H 2O 2Chemiluminescence takes place in the back; (6) chemiluminescent optical signals CMOS photodetector converts electric signal into, and carries out subsequent treatment and analysis.
(camber line ab, bc, cd, de, ef etc. are the repetitive structure unit that connects repeatedly to Fig. 4 rolling circle amplification reaction synoptic diagram; Each repetitive structure unit can both with ring-like DNA chain complementary pairing; Be the copy of ring-like DNA chain, for the purpose of distinguishing, be drawn as arc, actual is linear nucleotide chain).
Fig. 5 G-qudadruplex-hemin (DNAzyme) synoptic diagram (left side is space structure figure, and right figure is a reduced graph).
Long-chain DNA's is connected synoptic diagram behind Fig. 6 DNAzyme and the rolling circle amplification.
Fig. 7 DNAzyme catalytic chemistry luminescence-producing reaction formula.
Label among the figure: 1, DNAzyme (G-quadruplex-hemin); 2, detection molecules; 3, photoelectric switching circuit module; 4, photocurrent sensing circuit module; 5, analog to digital conversion circuit module; 6, rolling circle amplification extended chain; 7, target molecule; 8, silicon dioxide layer; 9, primer; 10, the repetitive structure unit of rolling circle amplification generation; 11, the linking arm of DNAzyme; 12, Hemin molecule;
Embodiment
The making of CMOS photodetector array.Each CMOS photodetector is integrated in photoelectric switching circuit module 3, photocurrent sensing circuit module 4 and analog to digital conversion circuit module 5 on the chip piece, has reduced noise, improves the ability that detects faint optical signal.Each chip size arrives the hundreds of micron at tens microns, and chip array is at interval at tens microns.Adopt based on the photodetector of CMOS technology on the N trap CMOS technology basis of SMIC 0.18 μ m, as photoelectric conversion module 3, convert light signal into photocurrent with the N+/Psub type photoelectric diode of CMOS process compatible.The maximum photoelectricity converting sensitivity of this photoelectric diode is 0.206A/W, and the peak response wavelength is 480nm, is 0.15A/W in the sensitivity of 420nm place.Because the CMOS photoelectric diode does not have internal gain, photoelectric transformation efficiency is low, therefore need improve detection sensitivity through integrated subsequent conditioning circuit.Photocurrent sensing circuit module 4 converts photocurrent into voltage signal, adopts pseudo-differential capacitor type transimpedance amplifier.The capacitor type transimpedance amplifier is made up of an amplifier, reset switch and integrating capacitor.Pseudo-differential sensing circuit module contains main detector and redundancy detector constitutes difference channel jointly.Main detector is mainly realized the photoelectric diode of opto-electronic conversion, and redundancy detector is the photoelectric diode of surface coverage metal, is used for eliminating the influence of dark current, thereby suppresses the common mode interference of CMOS photodetector.The voltage that photocurrent sensing circuit module 4 produces is analog quantity, makes its digitizing through analog to digital conversion circuit module 5.The analog-digital converter structure of 12-bit, 10-MS/s is adopted in analog-to-digital conversion module 5 designs.
The CMOS photodetector surfaces covers layer of silicon dioxide 8; Its finishing is mainly through APTES and glutaraldehyde chemical reaction; Concrete steps are following: earlier with ethanol and acetone photodetector silicon dioxide 8 surfaces, feed the APTES solution 1～2 hour of 2% (weight) then, clean with ethanol; Thereby formed the organosilicon strand in photodetector surfaces, this organosilicon strand contains uncle's ammonia.Add then and contain the glutaraldehyde of 2.5% (weight) and the NaBH of 4mM 3CN solution 0.8 ~ 1.2 hour, using pH then is that 7～7.6 PBS (phosphate buffer) cleans, thereby with pentanedial decoration to the organosilicon molecular surface.The significant protein PSA of prostate cancer is dripped to the photodetector surfaces that the organosilicon strand is modified through a model machine; Constant temperature is hatched about 30 minutes for 37 ℃; Using pH then is that 7～7.6 PBS (damping fluid) cleans repeatedly; Wash away unbinding protein, thereby form target molecule 7 in photodetector surfaces.Do not sealed with bovine serum albumin(BSA) (BSA) by the avtive spot of PSA branch subcovering.Add then goat-anti human monoclonal antibodies IgG-DNA with it 37 ℃ hatch half an hour.Wherein goat-anti human monoclonal antibodies IgG is a detection molecules 2, and the DNA chain of coupling couplet is a primer strand 9 with it.The molecule that falls not to be adsorbed with the PBS buffer solution elution; Adding rolling circle amplification reactant liquor (containing dNTP, phi29 damping fluid, phi29 polymerase and ring-like dna molecular chain) then hatched about 45 minutes; Thereby connect rolling circle amplification extended chain 6, the long-chain that this chain is made up of hundreds of the repetitive structure units 10 that connect repeatedly in detection molecules 2.After falling the rolling circle amplification reactant liquor with buffer solution for cleaning, add G-quadruplex-hemin solution, G-quadruplex chain molecular structure is following: 5 '- ATGCGCATGCTCAATTT GGGTAGGGCGGGTTGGG-3 '(SIQ.ID.NO.1); Wherein drawing horizontal line partly is exactly G-quadruplex; Being linked to each other by three continuous guanines forms specific molecule inner injection and closes structure, and with hemin molecule 12 formation G-quadruplex-hemin (being DNAzyme) structures 1, schematic arrangement is seen Fig. 5.At G-quadruplex molecular structure bend partly is DNAzyme linking arm 11, repetitive structure unit's 10 complementary pairings in linking arm 11 and the rolling circle amplification product, thus the DNAzyme molecule 1 is attached on the rolling circle amplification extended chain 6, see Fig. 6.The DNAzyme molecule 1 has the luminous function of HRPO catalytic chemistry, and the luminous reaction equation of its catalytic chemistry is seen Fig. 7.The optical signals CMOS photodetector that chemiluminescence produces converts electric signal into, and carries out the follow-up signal analysis.Because chemiluminescence intensity is relevant with the concentration of detection molecules 1, and there are the specificity relation in 7 of detection molecules 1 and target molecules, thereby realize target molecule 7 is carried out qualitative and quantitative analysis.Because during this chip design; Adopt the array of CMOS photodetector; And target molecule 7 also is the curing of array point sample; Therefore can be at arrayed optical electric explorer zones of different point sample different target molecule 7, through each detector in the photodetector array is carried out the chemiluminescence signal analysis, thereby different target molecule 7 is discerned.

Claims (9)

1.一种高灵敏度的集成CMOS光学生物芯片，其特征在于该芯片包括： 1. A highly sensitive integrated CMOS optical biochip, characterized in that the chip comprises: （1）一种基于大规模集成电路技术制备的CMOS光电探测器； (1) A CMOS photodetector based on large-scale integrated circuit technology; （2）固定于CMOS光电探测器表面的目标分子； (2) Target molecules immobilized on the surface of CMOS photodetectors; （3）可与目标分子发生特异性相互作用的检测分子，实现对目标分子进行识别；所述检测分子含有一引物，引发一种或者多种滚环扩增的复制产物，该滚环扩增的复制产物仍然连接在检测分子表面； (3) A detection molecule that can specifically interact with the target molecule to recognize the target molecule; the detection molecule contains a primer that triggers one or more replication products of rolling circle amplification, and the rolling circle amplification The replication product is still attached to the surface of the detection molecule; （4）G-quadruplex-hemin复合结构，通过连接臂固定在滚环扩增的复制产物上； (4) G-quadruplex-hemin composite structure, which is fixed on the replication product of rolling circle amplification through the tether; （5）在G-quadruplex-hemin催化下，luminol和双氧水发生化学发光，产生光信号，由CMOS光电探测器进行光电转换，实现一种或者多种的目标分子的鉴定。 (5) Under the catalysis of G-quadruplex-hemin, luminol and hydrogen peroxide undergo chemiluminescence to generate light signals, which are converted by CMOS photodetectors to realize the identification of one or more target molecules. 2.如权利要求1所述的集成CMOS光学生物芯片，其特征在于所述CMOS光电探测器集成了光电转换电路模块、光电流读出电路模块和模数转换电路模块；其中，所述的光电转换电路模块为阵列化的CMOS工艺的光电二极管、CMOS工艺的雪崩光电二极管或者CMOS工艺的光电三极管；所述的光电流读出电路模块为电阻性跨阻抗放大器或者电容性跨阻抗放大器，它将光电流转换为电压信号；所述的模数转换电路模块是将光电流读出电路模块产生的电压信号转换为数字信号，便于后续进一步数字化处理。 2. The integrated CMOS optical biochip as claimed in claim 1, wherein said CMOS photodetector has integrated a photoelectric conversion circuit module, a photocurrent readout circuit module and an analog-to-digital conversion circuit module; wherein said photoelectric The conversion circuit module is a photodiode of an arrayed CMOS process, an avalanche photodiode of a CMOS process, or a phototransistor of a CMOS process; the photocurrent readout circuit module is a resistive transimpedance amplifier or a capacitive transimpedance amplifier, which will The photocurrent is converted into a voltage signal; the analog-to-digital conversion circuit module converts the voltage signal generated by the photocurrent readout circuit module into a digital signal, which is convenient for subsequent further digital processing. 3.如权利要求1所述的集成CMOS光学生物芯片，其特征在于所述目标分子为核酸、寡核苷酸链或者多核苷酸链。 3. The integrated CMOS optical biochip according to claim 1, characterized in that the target molecule is a nucleic acid, an oligonucleotide chain or a polynucleotide chain. 4.如权利要求3所述的集成CMOS光学生物芯片，其特征在于所述检测分子为核酸、寡核苷酸链或者多核苷酸链，该检测分子有一部分能与所述的目标分子互补配对，另一部分作为引物，产生一种或者多种滚环扩增的复制产物。 4. integrated CMOS optical biochip as claimed in claim 3, is characterized in that described detection molecule is nucleic acid, oligonucleotide chain or polynucleotide chain, and this detection molecule has a part to be complementary pairing with described target molecule , and the other part serves as a primer to generate one or more replication products of rolling circle amplification. 5.如权利要求1所述的集成CMOS光学生物芯片，其特征在于所述目标分子为抗原/抗体、多肽或者蛋白质。 5. The integrated CMOS optical biochip according to claim 1, characterized in that the target molecule is an antigen/antibody, polypeptide or protein. 6.如权利要求5所述的集成CMOS光学生物芯片，其特征在于所述检测分子为抗体/抗原或者其他配体，该检测分子与所述的目标分子能特异性相互作用而结合在一起，而且该检测分子修饰有一段引物，以产生一种或多种滚环扩增的复制产物。 6. The integrated CMOS optical biochip as claimed in claim 5, wherein the detection molecule is an antibody/antigen or other ligands, and the detection molecule can specifically interact with the target molecule to bind together, Furthermore, the detection molecule is modified with a primer to generate one or more replication products of rolling circle amplification. 7.如权利要求1所述的集成CMOS光学生物芯片，其特征在于所述滚环扩增的复制产物是线性扩增复制产物。 7. The integrated CMOS optical biochip according to claim 1, characterized in that the replication product of the rolling circle amplification is a linear amplification replication product. 8.如权利要求1所述的集成CMOS光学生物芯片，其特征在于所述G-quadruplex-hemin是由含多鸟嘌呤（G）核苷酸链分子内形成的quadruplex结构，与hemin复合形成的具有过氧化酶催化功能的结构。 8. The integrated CMOS optical biochip according to claim 1, characterized in that the G-quadruplex-hemin is composed of a quadruplex structure formed in the molecule containing polyguanine (G) nucleotide chains, and compounded with hemin Structure with peroxidase catalytic function. 9.如权利要求1所述的集成CMOS光学生物芯片，其特征在于所述连接臂是一寡核苷酸链，通过碱基互补配对方法连接到所述的滚环扩增的复制产物中。 9. The integrated CMOS optical biochip according to claim 1, characterized in that the connecting arm is an oligonucleotide chain, which is connected to the replication product of the rolling circle amplification by complementary base pairing.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104774921A (en) * 2015-01-27 2015-07-15 济南大学 Chemiluminescent sensor for detecting trivalent arsenic, and manufacturing method thereof

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102732610B (en) * 2012-03-23 2014-01-29 章晓联 Visualized detection probes and application thereof in tuberculosis rifampicin resistance mutation detection
CN118853850A (en) * 2018-12-01 2024-10-29 深圳华大智造科技股份有限公司 Methods and structures for improving light collection efficiency of biosensors
CN114544965B (en) * 2020-11-11 2023-04-28 艾克发(北京)生物技术有限公司 Multiple signal amplification system and application thereof in immunoadsorption competition method detection
CN116519618B (en) * 2023-06-28 2023-09-22 深圳高性能医疗器械国家研究院有限公司 Optical biosensing module and optical biosensing device

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE414169T1 (en) * 1998-03-05 2008-11-15 Johnson & Johnson Res Pty Ltd METHODS FOR DETECTING NUCLEIC ACIDS USING ZYMOGENS AND ASSOCIATED KITS
WO2003024314A2 (en) * 2001-09-19 2003-03-27 The Regents Of The University Of Michigan Methods and compositions for detection of single nucleotide polymorphisms
CN100463973C (en) * 2006-09-30 2009-02-25 东南大学 Molecular seal sequencing device and sequencing method
CN101260431A (en) * 2008-04-24 2008-09-10 华南师范大学 Method for detection of transgenic species based on rolling circle amplification technique
CN101705277B (en) * 2009-11-13 2012-05-23 南开大学 A class of primers for detecting telomerase activity

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Joerg Albers ET AL.Electrical biochip technology–a tool for microarrays and continuous monitoring.《Anal Bioanal Chem》.2003,第377卷(第3期),521–527. *
刘青杰等.滚环DNA 扩增技术及其应用.《辐射研究与辐射工艺学报》.2007,第25 卷(第1 期),5-9. *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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