CN1408884A - Device and method for detecting gene sequence - Google Patents
Device and method for detecting gene sequence Download PDFInfo
- Publication number
- CN1408884A CN1408884A CN 01140901 CN01140901A CN1408884A CN 1408884 A CN1408884 A CN 1408884A CN 01140901 CN01140901 CN 01140901 CN 01140901 A CN01140901 A CN 01140901A CN 1408884 A CN1408884 A CN 1408884A
- Authority
- CN
- China
- Prior art keywords
- gene
- chip
- gene sequence
- reaction
- detecting
- 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.)
- Granted
Links
Images
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The present invention provides a device and a method for detecting gene sequence, combines detecting system based on nano particle principle and electric field device to control and speed micro matrix detection and provides an autoamtic control process via analysis of the feedback signal of nano particle probes on the chip. The present invention also relates to the relevant gene sequence detecting method. The present invention also provides the autoamtic feedback and automatic regulation device and method for the crossing and de-crossing process of the micro matrix gene chip. The present invention has high detection speed, high sensitivity and low cost compared with fluorescent probe method.
Description
Invention field
The present invention relates to the apparatus and method of detecting gene sequence, more specifically, relate to the apparatus and method of utilizing electronics biological gene chip to come detecting gene sequence.
Background of invention
The DNA gene chip is that DNA with hundreds of, thousands of or tens thousand of somes sub-threads is as probe.Employed DNA mainly contains two kinds: Nucleotide and existed with gene pool in complementary nucleotide (cDNA).They are formed on the chip with highdensity dot matrix.
Micromatrix DNA gene chip is applied to diagnosing dissimilar diseases and medically studies with the pharmacological gene later stage at present.As long as with the micromatrix bioprobe on the chip piece, just can handle the data on a large amount of genes and the molecular science, particularly about genetic gene mutation and expression.So just, the research and the performance history of diagnosis inherited disease and promotion medicine of future generation can have been accelerated.This can also help to find out the mechanism of disease and drug reaction on molecular level.
Now, the detecting probe that is used for micromatrix chip and other gene chip is the fluorescent sign.Fluorescent molecule Cy3 and Cy5 are arranged on the probe, detected so can utilize its fluorescent that sends.The fluorescent detection system is quite expensive.This has limited this scientific and technological widespread use, especially at methods for clinical diagnosis.In some cases, sample need pass through the amplification of Polymerase Chain Reaction in advance, could utilize the fluorescent probe to go to detect.
Before several years, Nanogen, (SanDiego, CA USA) have proposed to use some disclosed technical knowledges to produce with the fluorescent probe with electrochemical strength and have come controlling gene chip prototype Inc..Their instrument has utilized the process that the fluorescent signal goes to control hybridization and impurity elimination friendship of surveying.This instrument (NanoChip
TMMolecular Biology Workstation) principle is with surveying luminous above-mentioned hybridization and the impurity elimination friendship process controlled of fluorescent.NanoChip
TMChip is that the electronics of commercial unique existence quickens the micromatrix chip.The capacity of chip is every 100 gene probes.Described that workstation is allowed and is utilized electrochemical strength to go to accelerate to hybridize the process of handing over impurity elimination.Electrification strength is to be used for guiding thymus nucleic acid in the detected sample to the discrete electrode, changes the process of hybridization and impurity elimination friendship with this.In fluorescent detector at that time, there is its technical benefit in this system.
But its harm also clearly.At first, must before electrification guiding and hybridization program afterwards, utilize the amplification of fluorescent Polymerase Chain Reaction in advance owing to detect the gene content of sample, and need on amplified material, add vitamin H.Like this, detected result just false positive or false negative might occur.Because in amplification process, have basic error.These errors are that the check and correction sum of errors that comes from the amplification procedure is inserted incorrect Nucleotide.The price of adding the Polymerase Chain Reaction detecting instrument has also limited this The Application of Technology.Next is that Polymerase Chain Reaction amplifies sample in advance and needs the long time, and is not suitable for scene (on-site) and uses, and for example clinic, food, environment or other need the high test of susceptibility.The 3rd, the cost of fluorescent detector far surpasses the gene chip detector of other type.The 4th, the process of electrochemical strength guiding is very time-consuming.Under electrochemical strength guiding, a reaction probably needs one minute, and prepares a sample for NanoChip
TMWhat chip used can more extend total time.Because the every bit on the chip all must will repeat dna probe solution is added chip, electrochemical strength guides each dna probe and each electrochemical strength guiding reaction backlash to wash the process of indivedual probes off.In this example, 100 on the gene chip just must be repeated same program 100 times.Because complicated like this detection system, workload is very large, also therefore is not evolved into portable in present possibility in a short time.
Before the several years, Motorola, Inc. (USA) have demonstrated and have utilized conducting probe and electrochemical strength to go to control the method for a gene chip prototype.Utilize this method, cost is with respect to NanoChip
TMSystem has just reduced many.It also provides trace routine efficiently and need not the sample Polymerase Chain Reaction is done in advance amplification.In addition, the Motorola system also can real-time detection.Unfortunately, it is very complicated making the electric step of leading anoxic Nucleotide, and the characteristic of used material is more likely harmful to operator and environment.This manufacturing processed need with electricity lead traditional more expensive of ultimate ratio, so cost also increases immediately.
Therefore, expensive instrument, intensive application technician and process have lowered above system greatly in the coml magnetism.Therefore, in the technology of this area, wish to develop faster, more cheap and more high sensitive micromatrix row chip and relevant instrument.
Goal of the invention
Therefore the purpose of this invention is to provide a kind of energy detects segmental arrangement for detecting of gene order and method fast and reliablely.
That our another goal of the invention provides is faster, more cheap, the automatic detection instrument of high sensitive, the biochip used easily more.The price of chip will significantly reduce, so the price of Auto-Sensing and monitoring instrument also will significantly reduce.
Gene chip has purposes widely, the application's method with chip arrangement for detecting for different purposes provide an excellence, platform flexibly.
Summary of the invention
Therefore in sum, the invention provides a kind of device of detecting gene sequence, it combines based on the detection system of nanoparticle principle with electric field and controls and accelerate the device of the detecting process of micromatrix, and the feedback signal of the nanoparticle probe on can analysis chip and control these processes automatically.The invention still further relates to method according to the said apparatus detecting gene sequence.The invention relates to the micromatrix gene chip has automatic feedback and automatic adjustment system in the process of hybridization and impurity elimination friendship apparatus and method.
Most biomolecules has positive charge or negative charge naturally, orientation movement can occur under effect of electric field.Therefore each reflecting point (that is, each single-stranded dna fragment) at gene chip adds electric field, can quicken the speed that moves and accelerate DNA combination (hybridization) of dna fragmentation to be measured to gene chip.Under the control of device of the present invention, fast 1000 times of the hybridization speed of dna fragmentation than the hybridization speed of the natural method of routine.
Utilizing the nanoparticle probe to remove to survey bio signal once was used for hybridizing in position research and removed to survey gene and thymus nucleic acid.Now, it by the applicant as the detecting probe on the gene chip.
The cost that utilizes the nanoparticle probe technique to reduce to purchase detector instrument and increase the range of application of micromatrix chip is allowed that medical diagnosis carries out a common clinic, and be need not to send to the laboratory that has particular device.Detection system based on the nanoparticle principle provides than the susceptibility of fluorescent probe height with hundred times.In addition, this system also can be with some better simply Detecting devices, as the black and white scanner.These scanners can remove detection signal with the form of the black and white color (gray scales) of a scope.Therefore, the nanoparticle detection system provides above benefit, and existing fluorescent probe be can not provide.
In the application's scheme, utilize one section single-stranded dna fragment, design its sequence and target sequence complementation, can hybridize, that is, the DNA of demarcation and target dna are interosculated, relend the mensuration that helps the nanoparticle probe and detect target dna and whether exist.
Therefore, according to the device that is used for detecting gene sequence of the present invention, comprising:
1. reaction chamber provides the place that makes gene chip and testing gene serial response;
2. gene chip contains gene probe corresponding with the testing gene sequence and electrode array, and the substrate of gene chip can be made by glass, silicon and/or plastics;
3. the electric field bringing device is applied to gene chip with electric current, to quicken the speed that moves and accelerate DNA combination (hybridization) of dna fragmentation to be measured to gene chip;
4. gene order (being sample) adding set adds the testing gene sequence to reaction chamber;
5. nanoparticle probe adding set adds and contains the appearance liquid of nanoparticle probe to reaction chamber;
6. stabilized light source, infrared rays, ultraviolet ray, laser and visible light all can be light source.The accent that this light source also can be made power, but when detecting, light source needs to send the light of strength of stability;
7. detector, the color signal in the detection reaction chamber changes; Detector can be made up of CCD camera.The image that Kamera is taken gained is sent to amplifier, delivers to controller then; Detector also can be formed by other suitable light-sensitive detector.
8. controller, the signal that comes according to detector, thereby the speed of the temperature of strength of electric field that control applies and reaction chamber control reaction, and the order output of handling the input of every data and formulating every program.It can be formed by computer, controls with the object oriented language program software.
According to the device that is used for detecting gene sequence of the present invention, can also comprise: signal amplifies the liquid adding set, is used to add signal and amplifies liquid, to strengthen the detection signal of nanoparticle, makes detected result more obvious; Reaction chamber of the present invention can contain heating unit can regulate its temperature, comprising: hygrosensor, and the temperature that is used on the detection chip arrives interface system to data transmission; And well heater, be used to make each reaction solution before entering the chip reaction chamber, liquid is promoted to suitable temperature of reaction.
Below simple structure and the principle of work thereof of describing gene chip.The gene chip that the present invention uses comprises one by glass, silicon or plastic substrate, and electronic circuit and electrode array are arranged in substrate.On electrode, then have thymus nucleic acid, complementary DNA (cDNA) or other oligonucleotide probe.On gene chip, also contain a bar code area, storage and its structure and the relevant information of gene fragment on it.
Electric field with chip places the electronics clamp circuit by feedback detection system repacking to be produced under specific experiment condition, can cause the process of hybridization and impurity elimination friendship, thereby produce elite property signal.The nanoparticle detection system just can detect these signals.Described system carries out the specificity test to target gene and RNA sequence is tested by 5 ' the tail utmost point or 3 ' tail utmost point inspection and by various oligonucleotide probe.Device of the present invention combines gene chip and utilizes electrochemical strength to go to quicken to hybridize the process of handing over impurity elimination and utilize the nanoparticle probe mark.
In the solution of the present invention, according to the difference of the gene probe that loads on the gene chip, can be used to discern the range gene sequence, thereby can detect various diseases, for example: the gene order of hepatitis B virus, cancer cells, transgenic cell, tissue matching etc., and gene sequencing etc.
The invention still further relates to and utilize the nanoparticle probe to go to implement nucleic acid preface inspection analysis.This analytical applications electric field quicken nanoparticle probe mark varitrol.In addition, can implement also on this chip that the double focusing compound is synthetic, antibody/antigen reaction and other clinical diagnosis function.
The present invention also can be applicable to non-clinical applications such as genetically modified food detection, environmental pollution detection, water quality detection, Animal diseases detection.
The invention still further relates to a kind of method of utilizing video nanoparticle detection system and electronics biological gene chip detecting gene sequence, it may further comprise the steps:
1. form the gene chip that contains the dna fragmentation corresponding with the testing gene sequence, it contains a bar code area of substrate, dna fragmentation and the electrode array information relevant with the gene fragment on it with its structure with storage.
2. the reagent mix that makes said gene chip and tested person applies electric field in the reaction process kind reaction is quickened so that dna fragmentation on the said gene chip and testing gene serial response.
3. when reaction, add the solution that contains the nanoparticle probe.
4. observe the expressed colour-change of chip surface, judge whether the reagent of tested person contains the testing gene sequence.
5. according to above-mentioned colour-change, the electric field of control reaction and other parameter such as temperature, light source etc. are with the speed of control reaction.
The working process and the principle of gene chip detection method of the present invention are described below.
At first, the gene chip of suitably being furnished with the barcode data is carried in the system, computer reads the data of barcode immediately, cleans and start-up procedure so that load the software and the order instrument of correlation detection program.Meanwhile, computer display operation personnel import relevant material and confirm test event (as data such as name, age, sex, numberings), so that publish the result after a while.
The operator places test sample book in the instrument with needle tubing or screw socket centrifuge tube, afterwards just with unattended operation.Clean gene chip, put an amount of damping fluid then into, make hybridization after a while.The test sample book of preload is injected in the chip, imported fixed current immediately and make electrification and quicken hybridization.
Because DNA is electronegative, under effect of electric field, dna fragmentation just pushes be placed in advance probe on the electrode under the effect by electrochemical strength to make hybridization.Tens of seconds to after several minutes, crossover process finishes, just flushing residue and the sample of hybridization not, and then add the nanoparticle probe solution, similarly import fixed current, quicken hybridization, make the position of existing hybridization just now by electrochemical strength, mark with the nanoparticle probe, the result of hybridization can be detected.
After several minutes, the flushing chip, effect is that other nanoparticle probe that does not carry out chemical process is cleaned up.Add the nanoparticle signal again and amplify liquid, the nanoparticle volume is increased, make signal more obvious, easier detected equipment is surveyed.Whole signal amplification process takes several minutes, need carry out in the dark, and this is because amplifying signal solution is photosensitive.After reaction finishes, clean chip again.Check with the CCD image acquisition system whether crossover process is normal, enters anti-crossover process then.
The input fixed current but with opposite electric charge (being negative charge) in chip and controlled temperature because this process is that the dna fragmentation of incorrect hybridization is removed away, temperature is the variable of major control.And the carrying out that this process is just quickened in the electric current supply of negative pole.Chip is done regularly to clean, make CCD camera do supervision in real time well, need to determine whether the change temperature of reaction.After having passed through real-time feedback trace routine, whole testing process comes to an end.Can print out report, the record entire reaction course.
The apparatus and method of utilizing electronics biological gene chip to come detecting gene sequence of the present invention, its advantage is:
First aspect is to go to accelerate the process of detecting gene sequence with electric field controls nanoparticle probe micromatrix, and detection speed significantly improves.
Second aspect is than the detection method of using the fluorescent probe higher susceptibility to be arranged.
The third aspect is lower than the cost of the detection system of traditional use fluorescent probe.
Fourth aspect is to compare with the detection system of using the fluorescent probe to omit the step that some Polymerase Chain Reactions amplify, this can simplify the equipment operation in the laboratory simultaneously, and can reduce the false positive results that program produced that amplifies at traditional Polymerase Chain Reaction.
By understanding technical scheme of the present invention and advantage better with reference to detailed embodiment of the present invention and accompanying drawing.
The accompanying drawing summary
Fig. 1 is the structured flowchart of the device of detecting gene sequence of the present invention;
Fig. 2 is the structural representation of gene chip of the present invention;
Preferred embodiment is described
The preferred embodiments of the present invention are described with reference to the accompanying drawings.
With reference to accompanying drawing 1, a device according to detecting gene sequence of the present invention has been described, wherein gene chip is placed in the reaction chamber.Reaction chamber and the electric field bringing device in the reaction chamber, gene order (being sample) adding set and nanoparticle probe adding set do not draw among the figure.In fact electric field can perhaps apply by an electrostatic field or electromagnetic field by applying on the electrode that voltage is applied to gene chip, and its size is that the gene order (being sample) that is enough to make interpolation takes place significantly directed mobile just passable.The nanoparticle probe is the form with solution, joins in the reaction chamber after gene chip and gene order (being sample) hybridization to be measured.Here use lamp as the light source irradiation gene chip, with the colour-change of CCD detection gene chip, grey scale change in other words.Stepper-motor among the figure is the focusing that is used for controlling the CCD detector.Before the CCD detector spectral filter is arranged, effect is filtering stray light and unwanted light, improves the tolerance range of detector.The signal of CCD amplifies through an amplifier, delivers to controller by interface circuit again.
In reaction chamber, also contain having heaters and Temperature Detector, be used for the speed of hybridization between gene fragment on the controlling gene chip and the gene fragment to be measured, and nanoparticle probe and gene chip in conjunction with speed.They are also controlled by interface circuit by controller.
The damping fluid 1 and 2 of Fig. 1 below is applied in the reaction chamber by pump, and they are that a kind of signal amplifies liquid, are used to strengthen the strength of signal of nanoparticle probe, make the result of reaction be easier to detected.
Fig. 2 is a kind of surface view of gene chip.Middle portion is the gene order fragment, and peripheral part is an electrod-array.When being applied to voltage on the electrod-array, therefore intermediary gene order fragment also has electromotive force, can attract gene fragment to be measured directed mobile to gene chip, thereby accelerate hybridization speed.
As previously mentioned, the gene order fragment on the gene chip and the form and the kind of electrod-array can change along with the difference of gene fragment to be measured.
According to the apparatus and method of detecting gene sequence of the present invention, can significantly accelerate the speed of hybridization and detection, lowered cost simultaneously.
Those of ordinary skill in the art can make various changes and improvement in the technology of such scheme and spirit, these changes and improving all should be regarded as falling within the application's the scope of claim.
Claims (17)
1. the device of a detecting gene sequence comprises:
A reaction chamber provides the place that makes gene chip and testing gene serial response;
A gene chip contains gene probe corresponding with the testing gene sequence and electrode array, a bar code area of the information relevant with the gene fragment on it with the structure of gene chip with a storage;
An electric field bringing device is applied to gene chip with electric field, to quicken the speed that moves and accelerate gene fragment hybridization of testing gene fragment to gene chip;
A gene order sample adding set adds the testing gene sequence to reaction chamber;
A nanoparticle probe adding set, interpolation contains the appearance liquid of nanoparticle probe to reaction chamber;
A stabilized light source can send infrared rays, ultraviolet ray, laser or the visible light of strength of stability;
A detector, the color signal in the detection reaction chamber changes;
A controller is according to the signal that detector comes, the strength of electric field that control applies and the speed of response of reaction chamber.
2. according to the device of the detecting gene sequence of claim 1, it is characterized in that also comprising: signal amplifies the liquid adding set, is used to add signal and amplifies liquid, to strengthen the detection signal of nanoparticle, makes detected result more obvious.
3. according to the device of the detecting gene sequence of claim 1, it is characterized in that described reaction chamber can contain heating unit its temperature can be regulated, and comprise: hygrosensor is used for temperature on the detection chip being sent to controller; And well heater, be used to make each reaction solution before entering the chip reaction chamber, liquid is promoted to suitable temperature of reaction.
4. according to the device of the detecting gene sequence of claim 1, it is characterized in that described electric field bringing device can directly be connected or electromagnetic coupled or condenser coupling with described gene chip, so that electric field is applied to gene chip.
5. according to the device of the detecting gene sequence of one of claim 1-4, it is characterized in that described controller can be the computer that is equipped with by the object oriented language written program.
6. according to the device of the detecting gene sequence of one of claim 1-4, it is characterized in that the difference along with the gene fragment that will survey, the gene fragment on the described gene chip can be the different gene fragment corresponding with the gene fragment that will survey.
7. according to the device of the detecting gene sequence of one of claim 1-4, it is characterized in that the difference along with the gene fragment that will survey, described nanoparticle probe can be the different nanoparticle probe corresponding with the gene fragment that will survey.
8. according to the device of the detecting gene sequence of one of claim 1-4, it is characterized in that described detector is a CCD shooting acquisition system, the colour-change of its observing response liquid judges whether the reagent of tested person contains the testing gene sequence.
9. the device of detecting gene sequence according to Claim 8 is characterized in that described controller according to above-mentioned colour-change, and the electric field of control reaction and other parameter such as temperature, light source are with the speed of control reaction.
10. the method for a detecting gene sequence, it may further comprise the steps:
Formation contains the gene chip of the dna fragmentation corresponding with the testing gene sequence, and it contains a bar code area of substrate, dna fragmentation and the electrode group information relevant with the gene fragment on it with its structure with storage;
The reagent mix that makes said gene chip and tested person applies electric field reaction is quickened so that dna fragmentation on the said gene chip and testing gene serial response in reaction process;
When reaction, add the solution that contains the nanoparticle probe;
Observe the expressed colour-change of chip surface, judge whether the reagent of tested person contains the testing gene sequence;
According to above-mentioned colour-change, make feedback control or impurity elimination friendship process is controlled.
11. method according to the detecting gene sequence of claim 10, be characterised in that: it is characterized in that also comprising: after solution that adding contains nanoparticle is as the step of nanoparticle probe, comprise that also signal amplifies liquid and adds step, be used to add signal and amplify liquid, to strengthen the detection signal of nanoparticle, make detected result more obvious.
12. method according to the detecting gene sequence of claim 10, it is characterized in that in described reaction process, can making its temperature to regulate, and the temperature on the detection chip and be sent to controller, with make each reaction solution before entering the chip reaction chamber, liquid is promoted to the step of suitable temperature of reaction.
13. method according to the detecting gene sequence of claim 10, it is characterized in that described described in reaction process, apply can utilize in the step that electric field quickens reaction the electric field bringing device directly is connected or electromagnetic coupled or condenser coupling with described gene chip, so that electric field is applied to gene chip.
14. the method according to the detecting gene sequence of one of claim 10-13 is characterised in that the difference along with the gene fragment that will survey, the gene fragment on the described gene chip can be the different gene fragment corresponding with the gene fragment that will survey.
15. the method according to the detecting gene sequence of one of claim 10-13 is characterised in that the difference along with the gene fragment that will survey, described nanoparticle probe can be the different nanoparticle probe corresponding with the gene fragment that will survey.
16. according to the method for the detecting gene sequence of one of claim 1-4, be characterised in that the colour-change of using CCD shooting acquisition system to come observing response liquid, judge whether the reagent of tested person contains the testing gene sequence.
17., it is characterized in that in the step of described speed in described control reaction that according to above-mentioned colour-change, the electric field of control reaction and other parameter such as temperature, light source are with the speed of control reaction according to the method for the detecting gene sequence of claim 16.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01140901 CN1258602C (en) | 2001-09-22 | 2001-09-22 | Device and method for detecting gene sequence |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01140901 CN1258602C (en) | 2001-09-22 | 2001-09-22 | Device and method for detecting gene sequence |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1408884A true CN1408884A (en) | 2003-04-09 |
| CN1258602C CN1258602C (en) | 2006-06-07 |
Family
ID=4676024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 01140901 Expired - Fee Related CN1258602C (en) | 2001-09-22 | 2001-09-22 | Device and method for detecting gene sequence |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1258602C (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100516212C (en) * | 2004-05-07 | 2009-07-22 | 柯尼卡美能达医疗印刷器材株式会社 | Testing microreactor, testing device and testing method |
| CN1886663B (en) * | 2003-11-27 | 2010-08-18 | 爱信精机株式会社 | Biometric information check system |
| CN102174384A (en) * | 2011-01-05 | 2011-09-07 | 深圳华因康基因科技有限公司 | Method and system for controlling sequencing and signal processing of gene sequencer |
| CN103092090A (en) * | 2012-09-14 | 2013-05-08 | 盛司潼 | Sequencing control system |
| CN111040942A (en) * | 2019-12-05 | 2020-04-21 | 深圳清华大学研究院 | Gene sequencing device and gene sequencing method |
| CN112098493A (en) * | 2020-09-15 | 2020-12-18 | 绍兴市达冷肯生物科技有限公司 | Electrochemical gene detection device and method |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102146442B (en) * | 2010-12-31 | 2014-10-22 | 深圳华因康基因科技有限公司 | Method and system for controlling sequencing process of gene sequencer |
-
2001
- 2001-09-22 CN CN 01140901 patent/CN1258602C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1886663B (en) * | 2003-11-27 | 2010-08-18 | 爱信精机株式会社 | Biometric information check system |
| CN100516212C (en) * | 2004-05-07 | 2009-07-22 | 柯尼卡美能达医疗印刷器材株式会社 | Testing microreactor, testing device and testing method |
| CN102174384A (en) * | 2011-01-05 | 2011-09-07 | 深圳华因康基因科技有限公司 | Method and system for controlling sequencing and signal processing of gene sequencer |
| CN102174384B (en) * | 2011-01-05 | 2014-04-02 | 深圳华因康基因科技有限公司 | Method and system for controlling sequencing and signal processing of gene sequencer |
| CN103092090A (en) * | 2012-09-14 | 2013-05-08 | 盛司潼 | Sequencing control system |
| CN103092090B (en) * | 2012-09-14 | 2015-04-08 | 盛司潼 | Sequencing control system |
| CN111040942A (en) * | 2019-12-05 | 2020-04-21 | 深圳清华大学研究院 | Gene sequencing device and gene sequencing method |
| CN111040942B (en) * | 2019-12-05 | 2023-06-27 | 深圳清华大学研究院 | Gene sequencing device and gene sequencing method |
| CN112098493A (en) * | 2020-09-15 | 2020-12-18 | 绍兴市达冷肯生物科技有限公司 | Electrochemical gene detection device and method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1258602C (en) | 2006-06-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210265018A1 (en) | Knowledge Distillation and Gradient Pruning-Based Compression of Artificial Intelligence-Based Base Caller | |
| US8023113B2 (en) | Biological analysis arrangement and approach therefor | |
| US20030168579A1 (en) | Signal offset for prevention of data clipping in a molecular array scanner | |
| CA2341896A1 (en) | Support for a method for determining an analyte and a method for producing the support | |
| CN1940511A (en) | Light amount measuring apparatus and light amount measuring method | |
| US20230343414A1 (en) | Sequence-to-sequence base calling | |
| CN1258602C (en) | Device and method for detecting gene sequence | |
| CN1793862A (en) | Optical detection method for membrane protein molecule interaction | |
| CN1245218A (en) | Solid-phase one-by-one base nucleic acid analysis method and its instrument | |
| EP2824444B1 (en) | Determination method, determination device, determination system, and program | |
| CN1605861A (en) | Preparation and detection method for electrochemical quantitative polymerase chain reaction detecting chip | |
| Marcy et al. | Innovative integrated system for real-time measurement of hybridization and melting on standard format microarrays | |
| WO1998008083A1 (en) | Method and apparatus for detecting predetermined molecular structures in a sample | |
| CN1886663A (en) | Biometric information check system | |
| US20050048551A1 (en) | Analyte evaluating device, method for evaluating analyte and method for manufacturing analyte evaluating device | |
| CN114088953B (en) | Drug target screening protein chip kit | |
| Attoye et al. | Electrochemical DNA Detection Methods to Measure Circulating Tumour DNA for Enhanced Diagnosis and Monitoring of Cancer | |
| JP2006300797A (en) | Biological data processor, biological data measuring method, program, recording medium and substrate | |
| EP3677690A1 (en) | Method and device for analysing nucleic acids | |
| WO2010024524A2 (en) | Nano-scale biochip scanner | |
| US20050026306A1 (en) | Method and system for generating virtual-microarrays | |
| US20040038214A1 (en) | Method and system for reading a molecular array | |
| CN1699601A (en) | Surface for detection of interaction between substances and corresponding sensor chip, sensing device and detection method | |
| Vo-Dinh | Multifunctional and multispectral biosensor devices and methods of use | |
| US20050238354A1 (en) | System, method, and product for increased signal and reduced noise detection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: HAIKANG LIFE SCIENCES CO., LTD. Free format text: FORMER NAME OR ADDRESS: HONGKONG GENE WAFER DEVELOPMENT CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: Hongkong China Shaukeiwan Kung Ngam Village Road No. 18 Hengtong resource center 8 floor Patentee after: Hai Kang Life Corp. Ltd. Address before: 2, Yip Yip Street, Kowloon, Hongkong Patentee before: Hongkang Gene Wafer Development Co., Ltd. |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1055318 Country of ref document: HK |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060607 Termination date: 20190922 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |