CN101201350A - Biochip system capable of rapidly hybridization and detection of biomolecule with high sensibility and method thereof - Google Patents
Biochip system capable of rapidly hybridization and detection of biomolecule with high sensibility and method thereof Download PDFInfo
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- CN101201350A CN101201350A CNA2007100593435A CN200710059343A CN101201350A CN 101201350 A CN101201350 A CN 101201350A CN A2007100593435 A CNA2007100593435 A CN A2007100593435A CN 200710059343 A CN200710059343 A CN 200710059343A CN 101201350 A CN101201350 A CN 101201350A
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Abstract
The invention relates to a biochip system and a method to cross and detect biomolecules quickly and sensitively. The biochip system comprises a lining board; an electrode array; and at least a variety of biomolecules arranged on electrodes, among electrodes, on a porous membrane arranged on or above the electrodes and/or on a cover board; a control system; at least a component system which can change the impedance, the capacitance, the electric current, the direction of current and/or the voltage of the electrodes or among the electrodes; and at least a detection component system which can detect the impedance, the capacitance, the signal to noise ratio, the resistance, the electric current and/or voltage change of the electrodes or among the electrodes. The electrode array is probably crossed with the substance or molecules to be detected in the solution touched. The methods concerned are electric assisted cross and electronic detection.
Description
Technical field
The invention belongs to life science and biological technical field, relate generally to be used for chemistry and biochemical analysis, chemistry and bio-sensing, the synthetic and miniature instrument that detects, relate in particular to the biochip system and the method that can fast high-sensitive carry out biomolecule hybridization, detection of a kind of biology, chemistry and medicine experiment detection range.
Background technology
Biochip is the new and high technology that grows up the eighties in last century, it melts microelectronics, biology, physics, chemistry, materialogy, computer science, forming processing technology is an one, can pair cell, DNA, biological components such as protein carry out accurately, the check and analysis of quick and large information capacity, treat in medical diagnosis on disease, the disease forecasting prevention, the new drug research exploitation, crop breeding, many-side such as environment measuring and food safety monitoring has extensive use, market potential is huge, becomes one of the most important growth point of international life science and biotechnology industry and focus of the competition.
Common biochip is divided three classes at present: the first kind is a micro-array chip, comprises genetic chip, protein chip, cell chip and organization chip; Second class is micro-fluidic chip (belonging to active chip), comprises all kinds of specimen preparation chips, polymerase chain reaction (PCR) chip, capillary electrophoresis chip and chromatogram chip etc.; The 3rd class is the integrated analytic system based on biochip, i.e. chip lab (Lab-on-chip)." chip lab " can be realized on the small chip being integrated in such as the pre-treatment of sample (sample), specimen preparation, determinand separation, reagent conveying, biochemical reaction, detection as a result etc., and rely on some detection methods such as electrochemical assay and optical detection, convert chemical signal to electric signal or optical signalling, machine or other signal processing apparatus make an explanation as calculated again.These micro integrated analytic systems are easy to carry, can be used for urgent occasion, field operation even are placed on the spacecraft.
Yet, before the biochip large-scale application, also have many difficult problems to need to solve, comprising: for the reduction of the discovery of the fundamental research of diseases such as cancer, gene, production cost, the detection of fast high-sensitive ground etc.Especially, the research and development that biochemical reaction and result thereof are detected at present both at home and abroad nearly all concentrate on to handle with fluorescence to be carried out sex change and is that results of hybridization detects with very expensive fluorescent scanning instrument or optical instrument to biochemical reaction.Therefore, be difficult to be used widely, especially be difficult to enter family, be difficult to individualize at aspects such as medical diagnosis on disease treatment, disease forecasting prevention, food safety monitorings based on the biochip of this class technology.
Chinese patent prospectus CN02112625.9 has related to a kind of collection of the biological chip fluorescent picture with filter wheel, and the scanning that is used for fluoroscopic image on the biochip detects.This system mainly is made up of the X-Y platform and the support of laser excitation light path, fluorescence receiving light path and placement biochip.Two laser beam in the laser excitation light path arrive same light path by light-combining prism, after passing the through hole at hollow total reflective mirror center, focus on a point on the biochip through laser condensing lens, laser excitation light path and two fluorescence receiving light paths are shared, by the two dimensional motion of X-Y platform, can obtain the two-dimentional fluoroscopic image on a plurality of biochips.
Chinese patent prospectus CN200410009044.7 discloses a kind of biochip test method and detection system thereof that light intensity detects in real time that have, in the exciting light light path, add an optical density dish, to adjust light intensity, an optical detection system is installed below slide holder, the light intensity of the light on the detected print of arrival that detection is sent by xenon source, this light intensity value has reflected the truth of excitation source light intensity really, this light intensity value record to some extent in computing machine, when this light intensity value change, computer system is judged according to the signal that testing circuit provides, in time take measures, adjust the exposure of optical density dish or adjustment print, to guarantee to detect the true and reliable of data.This invention both can be adjusted light intensity by the optical density dish, also can adjust the exposure of biological print, so just can avoid in biochip test changing the detection error that causes, guarantee that the detection data of biological chips detection system are true and reliable owing to the light intensity difference XOR homogeneity of exciting light sources.
Yet above-mentioned disclosed biochip and related detection method and detection system thereof all can be very expensive.
Chinese patent ZL01129100.1 discloses a kind of gene chip preparation method, is characterized in that a. has the dna probe point on the basic point of carrier of thin metal layer in spraying plating, finishes the fixing of DNA; The solution point that b. will contain electrochemical active group makes fixing DNA sample 5 ' end be with an electrochemical active group on fixing DNA surface; The structure of described dna probe is: 5 '-NH
2-(CH
2) n-
* * * * *++ ++ ++ ++ ++ ++ +++
* * * * *-(CH
2) n-SH-and the above-mentioned metal surface that has the electronic gene chip of electrochemical active group further is dipped in SH-(CH
2)
6Spend the night in-OH the solution, this invents resulting electronic gene chip is to adopt electronic detectors to detect the signal of genetic chip.
Chinese patent ZL01129104.4 relates to a kind of detection method of electronic gene chip, be characterized in that the genetic chip and the sample DNA that will have electrochemical active group hybridize, detect with of the variation of electronic detectors replacement fluorescent scanning instrument then, judge whether contain DNA fragment specific to be detected in the detected sample electric signal before and after the gene chip hybridization.
But this invention can not be widely used in biochip and carry out high-sensitivity detection.
Summary of the invention
The purpose of this invention is to provide a kind of low cost, high flux, fast, efficient, biomolecule with high sensibility hybridization, the biochip system that detects, to overcome the defective of existing biochip or its system.
Another object of the present invention provides a kind of quick biomolecule hybridization of implementing in this biochip system, carry out the method that biomolecule hybridization detects reliably, efficiently, in high sensitivity, to overcome the defective that exists in existing biomolecule hybridization, the detection method.
A distinguishing feature of the present invention is: the resulting biochip system of the present invention can be without fluorescent scanning instrument or optical instrument and is adopted electricity to help hybridization, detection of electrons; According to the present invention, can increase substantially hybridization speed, detection sensitivity and the degree of accuracy of existing biochip or its system, enlarge the range of application of existing biochip or its system significantly and enlarge its test sample kind.
Another distinguishing feature of the present invention is: whole technical proposal of the present invention is made up of biochip system and method two parts of biomolecule hybridization, detection, is applicable to biomolecule hybridization and detection high-throughout, any kind of.
Another distinguishing feature of the present invention is: biochip system of the present invention is easy to enter family, is easy to individualize, be easy to microminaturization, is easy to carry, and can be used for urgent occasion, field operation.
What the present invention relates to can carry out biomolecule hybridization, the biochip system that detects and method based on classical principle of electrophoresis by fast high-sensitive, both in electrolyte solution, charged particle under electric field action, with different speed to its phenomenon of electrically charged reverse direction migration; Also based on some classical results of study, for example: the migration velocity of solute is by its electrically charged number of institute and the decision of molecular weight size, also be subjected to the multiple factor affecting such as composition, character, p H value of damping fluid in addition, again for example: protein molecule is that existing acidic-group (COOH), has basic group (NH again
2) ampholyte, in a certain solution the positive and negative charge of being with equate that promptly the net charge of molecule equals zero, at this moment, protein is no longer mobile in electric field, the isoelectric point that this pH value of solution is this protein (isoelctric point, pI).If pH value of solution is in isoelectric point acid side, i.e. pH＜p1, then the protein belt positive charge moves to negative pole in electric field.If pH value of solution is in isoelectric point alkali side, i.e. pH＞p1, then the protein belt negative charge moves to positive pole.The pH of solution is far away more from p1, and net charge that particle is with is many more, and electrophoretic mobility is big more.
The inventor has considered that also electric current is by flowing across the base between the dna double chain, but not the flowing along the double helix chain like that of people's imagination, if the order that 4 kinds of bases are arranged among the DNA is changed the achievement in research recently that the speed of electric current also changes to some extent.
The biochip system that the present invention relates to comprises a liner plate, one has at least two electrode arrays that are arranged on liner plate surface or electrode inside, at least a being arranged on the electrode, between electrode, above them/on the perforated membrane of top and/or the cover plate, the biomolecule that may hybridize with test substance in the solution that will contact or molecule, a control system, at least one is connected with electrode, can make electrode or interelectrode impedance, electric capacity, electric current, the element system of direction of current and/or change in voltage and/or at least one are connected with electrode, energy detecting electrode or interelectrode impedance, electric capacity, signal to noise ratio (S/N ratio), resistance, the detecting element system of electric current and/or change in voltage; Wherein, liner plate is selected from macromolecular material, glass, pottery, silicon, mica or one or more the potpourri in them, and cover plate is selected from one or more in macromolecular material, biodegradation, inorganic material, the metal particle.
Cover plate can be one deck can be topped the film of whole or partial electrode array, also can be the film that one deck has open-work, so that electrode can be among the open-work.
Related perforated membrane is one or more layers compound, as to contain streptavidin, nucleic acid, amino acid, metal particle and/or enzyme molecule multiporous biological or organic polymer film; Its gross thickness greater than 1 nanometer less than 300 microns, average pore size less than 20 microns, porosity greater than 30%.
Related biomolecule comprises: through amplification, without in amplification, modified or not adorned DNA, RNA, protein, peptide class, polysaccharide, enzyme, nucleic acid, oligonucleotide, antigen/antibody, cell, virus, organic molecule, synthetic molecules, natural biological molecule, drug molecule, the compound one or more.
Related test substance or molecule comprise through amplification, without amplification, DNA, RNA, protein, peptide class, polysaccharide, enzyme, nucleic acid, oligonucleotide, antigen/antibody, cell, virus, organic molecule, synthetic molecules, natural biological molecule, drug molecule through particulate is modified or do not modified by particulate, in the compound one or more.Also comprise the chemical substance that some are little, as microbiotic, agricultural chemicals etc.
Comprise test substance or molecule in the solution that the present invention relates to, charged species, lithium boric acid, phosphate, borate contains the alkali solvent, contains sour solvent, water, deionized water and/or organic solvent.
Charged species comprises one or more in the oligonucleotide of being modified by particulate, amino acid, DNA, RNA, protein, peptide class, polysaccharide, nucleic acid or their fragment that has with the different electrical properties of solution.
Particulate comprises that diameter is greater than non-metal particle, metal particle, insulator, magnetic thing, the radiation of 1 nanometer less than 1000 nanometers.
The electrode that the present invention relates to or its link material are selected from solid-state or liquid metal, metallic compound, metal mixture and/or conduction high polymer.The surface configuration of electrode is to comprise interdigital random geometry; Wherein, electrode separation and/or interdigital spacing are less than 250 microns, and electrode diameter or interdigital width are less than 500 microns.
The electrode that the present invention relates to and then also comprise carbon nanotube electrode.
Electrode array involved in the present invention can have up to ten thousand electrodes, and the distribution of electrode can have rule, also can be random unordered.The electrode array can be by multi-group electrode, and single group electrode and/or single electrode are formed, and every group of electrode has at least two electrodes and/or accumulate an electrode.
Relate in the literary composition in the present invention, " between electrode " mean in the electrode array between any two electrodes, arbitrarily between electrode and other electrode, between some electrodes and some other electrode or in the electrode array between certain electrode/some electrode and the specific current electrode, and this above current electrode/top may not be provided with biomolecule.
Relate in the literary composition in the present invention, " electrode or its link material " can be selected from any conducting metal in principle, but is preferably copper, aluminium, gold, silver, platinum, tin.
The control system that the present invention relates to can be used for the initialization system operating parameter or distributes these operating parameters, connect alternative, expand element or system, report, analyte detection process or result.Control system can be an EPROM or a simple computer system.
The biomolecule hybridization that the present invention relates to, the method that detects comprise the following steps:
1) on perforated membrane that is provided with biomolecule and/or cover plate, puts into perforated membrane and/or cover plate and the electrode immersion solution that solution maybe will be provided with biomolecule;
2) before the detection of biological molecule contacts with solution or contact back but on the electrode before hybridizing/impedance, electric capacity, resistance, electric current and/or voltage;
3) select
Step (a): make in the electrod-array above wherein one or more/there is the electrode of certain biomolecule the top for anodal, other electrode is that the negative pole energising was not less than for 1 second (so that electronegative test substance or molecule are shifted to positive pole rapidly under the electroline effect between electric field, and with anodal above/biomolecule of upper fixed reacts, if both react, then produce the hydridization phenomenon, electric current on this electrode or impedance etc. then have to differ from be electric current electric current before the hydridization or impedance etc.), make again after the outage another or other above/electrode that the top is provided with atypical biomolecule is for anodal, other electrode, current electrode and/or to remove as anodal excessively electrode be that the negative pole energising was no less than for 1 second, class this, with above all/electrode that there are variety classes biomolecule or a setting in the top is one by one as anodal, other electrode, current electrode and/or to remove as anodal excessively electrode be the negative pole energising, all be no less than for 1 second each conduction time and electric current or impedance are changed according to biomolecule and/or particle species or size, help finish hybridization reaction;
Step (b): make in the electrod-array above wherein one or more/electrode of certain biomolecule is arranged is negative pole in the top, other electrode was not less than for 1 second (so that positively charged test substance or molecule are shifted to negative pole rapidly under the electroline effect between electric field for anodal energising, and with above the negative pole/biomolecule of upper fixed reacts, if both react, then produce the hydridization phenomenon, electric current on this electrode or impedance etc. then have to differ from be electric current electric current before the hydridization or impedance etc.), make again after the outage another or other above/electrode that the top is provided with atypical biomolecule is a negative pole, other electrode, current electrode and/or remove as anodal excessively electrode and be no less than for 1 second for anodal energising, class this, with above all/there is the electrode of variety classes biomolecule or setting the top one by one as negative pole, other electrode, current electrode and/or remove as anodal excessively electrode and be anodal energising, all be no less than for 1 second each conduction time and electric current or impedance are changed according to biomolecule and/or particle species or size, help finish hybridization reaction; Or
Step (c): repeating step (a) or step (b), or intersection carries out step (a) and step (b) helps finish hybridization reaction;
4) relatively by step 2) with step 3) or thereafter/remove behind the unreacting substance detected top/top is equipped with on the electrode of biomolecule/electric current, impedance, electric capacity, signal to noise ratio (S/N ratio), resistance and/or voltage, wherein, reset procedure comprises solvent, solution or the cataphoresis method of adopting; And/or
5) by top/top be equipped with on the electrode of biomolecule/electric current, impedance, electric capacity, signal to noise ratio (S/N ratio), resistance and/or change in voltage or change numerical value and determine material or molecular species and/or quantity in the solution identical with biomolecule.
The biochip system that the present invention relates to can form two interelectrode arch formations to strengthen detection signal in crossover process, improve detection sensitivity.Very little in spacing between electrodes, for example under the situation less than 1000 nanometers, biomolecule is not set between electrode, also can obtain interelectrode preferably arch formation.
Miniature heat and/or device for cooling, temperature control equipment can be set, can control the hydridization temperature of some hybridization reaction in the biochip system that the present invention relates to.
Description of drawings
Accompanying drawing 1 is the diagrammatic cross-section that is provided with the biochip system of biomolecule on a kind of perforated membrane on electrode involved in the present invention.
Accompanying drawing 2 is diagrammatic cross-sections that are provided with the another kind of biochip system of biomolecule on the perforated membrane on the electrode involved in the present invention.
Accompanying drawing 3 is diagrammatic cross-sections that a kind of electrode involved in the present invention is provided with the biochip system in the liner plate.
Accompanying drawing 5 is the synoptic diagram that produce the hybridization phenomenon on the biochip system involved in the present invention.
Embodiment
Accompanying drawing 1 to accompanying drawing 6 is synoptic diagram of the biochip system of several forms that spirit constitutes according to the present invention.But the biochip system that the present invention relates to is not limited in these legends.
To shown in the accompanying drawing 6, the embodiment of the invention comprises as accompanying drawing 1: liner plate (1), electrode (2,2a), perforated membrane (3), biomolecule (4) can make the element system (5) of electrode or interelectrode impedance, electric capacity, electric current, direction of current and/or change in voltage, control system (6), the detecting element system (7) of energy detecting electrode or interelectrode impedance, electric capacity, signal to noise ratio (S/N ratio), resistance, electric current and/or change in voltage, line (8), cover plate (9), test substance or molecule (10), particulate (11).
The present invention is further described below in conjunction with drawings and Examples, but the present invention is not limited in the embodiment declared range.
Embodiment 1
Biochip system as shown in Figures 1 and 2 comprises a liner plate (1), one has two electrodes (2 that are arranged on liner plate (1) surface, electrode array (not shown) 2a), a kind of electrode (2 that is arranged on, on the perforated membrane 2a) (3), the biomolecule (4) that may hybridize with test substance in the solution that will contact (not shown) or molecule (10), a control system (6), one by line (8) and electrode (2,2a) be connected, can make electrode or interelectrode impedance, electric capacity, electric current, the element system of direction of current and/or change in voltage (5), one by line (8) and electrode (2,2a) be connected, energy detecting electrode or interelectrode impedance, electric capacity, signal to noise ratio (S/N ratio), resistance, the detecting element system (7) of electric current and/or change in voltage.The difference of these two kinds of biochip systems is: the electrode connecting line of the biochip system shown in the accompanying drawing 1 (8) passes liner plate (1), and the electrode connecting line of the biochip system shown in the accompanying drawing 2 (8) is arranged on the liner plate (1).The set-up mode of these two kinds of lines (8) all is suitable for the biochip system that the present invention relates to.
Biochip system as shown in Figure 3 comprises a liner plate (1), one has two and is arranged on liner plate (1) electrode (2 inside, electrode array (not shown) 2a), a kind of electrode (2 that is arranged on, 2a) and on the perforated membrane (3) on the liner plate (1), the biomolecule (4) that may hybridize with test substance in the solution that will contact (not shown) or molecule (10), a control system (6), one by line (8) and electrode (2,2a) be connected, can make electrode or interelectrode impedance, electric capacity, electric current, the element system of direction of current and/or change in voltage (5), one by line (8) and electrode (2,2a) be connected, energy detecting electrode or interelectrode impedance, electric capacity, signal to noise ratio (S/N ratio), resistance, the detecting element system (7) of electric current and/or change in voltage.
Biochip system as shown in Figure 4 comprises a liner plate (1), one has two electrode arrays (not shown) that are arranged on the electrode (2) on liner plate (1) surface, a kind of electrode (2 that is arranged on, perforated membrane 2a) (3) is last and liner plate (1) upper cover plate (9), the biomolecule (4) that may hybridize with test substance in the solution that will contact (not shown) or molecule (10), a control system (6), one by line (8) and electrode (2,2a) be connected, can make electrode or interelectrode impedance, electric capacity, electric current, the element system of direction of current and/or change in voltage (5), one by line (8) and electrode (2,2a) be connected, energy detecting electrode or interelectrode impedance, electric capacity, signal to noise ratio (S/N ratio), resistance, the detecting element system (7) of electric current and/or change in voltage.
Biochip system as shown in Figure 5 be as shown in Figure 4, that carried out biomolecule (4) hybridization but do not produce electrode (2, the 2a) biochip system of the arch formation between.
Biochip system as shown in Figure 6 be as shown in Figure 4, carry out biomolecule (4) hybridize and produced electrode (2, the 2a) biochip system of the arch formation between.
1) on perforated membrane that is provided with biomolecule (4) (3) and/or cover plate (9), put into solution (not shown) maybe will be provided with the perforated membrane (3) of biomolecule (4) and/or cover plate (9) and electrode (2,2a) immerse solution (not shown);
2) before detection of biological molecule (4) contacts with solution (not shown) or contact back but electrode before hybridizing (2,2a) on/impedance, electric capacity, resistance, electric current and/or voltage;
3) make in the electrod-array (not shown) above wherein one or more/there is the electrode (2) of certain biomolecule (4) top for anodal, other electrode (2a) was not less than for 1 second (so that electronegative test substance or molecule (10) are shifted to positive pole rapidly under the electroline between electric field (not shown) effect for the negative pole energising, and with anodal above/biomolecule (4) of upper fixed reacts, if both react, then produce the hybridization phenomenon, electric current on this electrode (2) or impedance etc. then have to differ from be electric current electric current before the hydridization or impedance etc.), finish hybridization reaction;
4) relatively by step 2) with step 3) detected above/top is equipped with electric current, impedance, electric capacity, signal to noise ratio (S/N ratio), resistance and/or the voltage on the electrode (2) of biomolecule (4);
5) by electric current, impedance, electric capacity, signal to noise ratio (S/N ratio), resistance and/or change in voltage on the electrode (2) or change numerical value and determine material or molecule (10) kind and/or quantity in the solution (not shown) identical with biomolecule (4).
Embodiment 3 (embodiment)
On the PMMA liner plate, 2 platinum electrodes of spot printing, its diameter is about 150 microns, and spacing is about 120 microns; Spray the PS foam films that one decks contain golden particulate and biology enzyme at two electrode surfaces, its thickness is about 100 microns; Fixing DNA probe on the PS film; Itself and electrode are partly immersed with silver-colored particulate and through the solution of the same DNA of amplification, electrode with intrinsic dna probe is a working electrode, switches on to hybridizing in 0.5 minute, and the hybridization back is under the greenhouse, measure the current value variation of hybridization front and back down of 500mV voltage, this changing value is 11%.
Claims (10)
1. an energy fast high-sensitive carries out biomolecule hybridization, the biochip system that detects, it is characterized in that: this biochip system comprises a liner plate, one has at least two electrode arrays that are arranged on liner plate surface or electrode inside, at least a being arranged on the electrode, between electrode, above them/on the perforated membrane of top and/or the cover plate, the biomolecule that may hybridize with test substance in the solution that will contact or molecule, a control system, at least one is connected with electrode, can make electrode or interelectrode impedance, electric capacity, electric current, the element system of direction of current and/or change in voltage and/or at least one are connected with electrode, energy detecting electrode or interelectrode impedance, electric capacity, signal to noise ratio (S/N ratio), resistance, the detecting element system of electric current and/or change in voltage; Wherein, liner plate is selected from macromolecular material, glass, pottery, silicon, mica or one or more the potpourri in them, and cover plate is selected from one or more in macromolecular material, biodegradation, inorganic material, the metal particle.
2. the biochip system that energy fast high-sensitive according to claim 1 carry out biomolecule hybridization, detect, it is characterized in that: described perforated membrane is one or more layers compound, as to contain streptavidin, nucleic acid, amino acid, metal particle and/or enzyme molecule multiporous biological or organic polymer film; Its gross thickness greater than 1 nanometer less than 300 microns, average pore size less than 20 microns, porosity greater than 30%.
3. the biochip system that can fast high-sensitive carry out biomolecule hybridization, detect according to claim 1, it is characterized in that: described biomolecule comprises: through amplification, without in amplification, modified or not adorned DNA, RNA, protein, peptide class, polysaccharide, enzyme, nucleic acid, oligonucleotide, antigen/antibody, cell, virus, organic molecule, synthetic molecules, natural biological molecule, drug molecule, the compound one or more.
4. the biochip system that can fast high-sensitive carry out biomolecule hybridization, detect according to claim 1 is characterized in that: described test substance or molecule comprise through amplification, without amplification, DNA, RNA, protein, peptide class, polysaccharide, enzyme, nucleic acid, oligonucleotide, antigen/antibody, cell, virus, organic molecule, synthetic molecules, natural biological molecule, drug molecule through particulate is modified or do not modified by particulate, in the compound one or more.
5. the biochip system that energy fast high-sensitive according to claim 1 carry out biomolecule hybridization, detect, it is characterized in that: comprise test substance or molecule in the described solution, charged species, lithium boric acid, phosphate, borate, contain the alkali solvent, contain sour solvent, water, deionized water and/or organic solvent.
6. the biochip system that can fast high-sensitive carry out biomolecule hybridization, detect according to claim 5 is characterized in that: described charged species comprises one or more in the oligonucleotide of being modified by particulate, amino acid, DNA, RNA, protein, peptide class, polysaccharide, nucleic acid or their fragment that has with the different electrical properties of solution.
7. carry out the biochip system that biomolecule is hybridized, detected according to claim 4 or 6 described energy fast high-sensitives, it is characterized in that: described particulate comprises that diameter is greater than non-metal particle, metal particle, insulator, magnetic thing, the radiation of 1 nanometer less than 1000 nanometers.
8. the biochip system that energy fast high-sensitive according to claim 1 carry out biomolecule hybridization, detect, it is characterized in that: described electrode or its link material are selected from solid-state or liquid metal, metallic compound, metal mixture and/or conduction high polymer.
9. the biochip system that energy fast high-sensitive according to claim 1 carry out biomolecule hybridization, detect, it is characterized in that: the surface configuration of described electrode is to comprise interdigital random geometry; Wherein, electrode separation and/or interdigital spacing are less than 250 microns, and electrode diameter or interdigital width are less than 500 microns.
10. the method that biochip system as claimed in claim 1 carries out biomolecule hybridization, detects, it is characterized in that: its method comprises the following steps:
1) on perforated membrane that is provided with biomolecule and/or cover plate, puts into perforated membrane and/or cover plate and the electrode immersion solution that solution maybe will be provided with biomolecule;
2) before the detection of biological molecule contacts with solution or contact back but on the electrode before hybridizing/impedance, electric capacity, resistance, electric current and/or voltage;
3) select
Step (a): make in the electrod-array above wherein one or more/there is the electrode of certain biomolecule the top for anodal, other electrode is that the negative pole energising was not less than for 1 second, make again after the outage another or other above/electrode that the top is provided with atypical biomolecule is for anodal, other electrode, current electrode and/or to remove as anodal excessively electrode be that the negative pole energising was no less than for 1 second, class this, with above all/electrode that there are variety classes biomolecule or a setting in the top is one by one as anodal, other electrode, current electrode and/or to remove as anodal excessively electrode be the negative pole energising, all be no less than for 1 second each conduction time, helps finish hybridization reaction;
Step (b): make in the electrod-array above wherein one or more/electrode of certain biomolecule is arranged is negative pole in the top, other electrode was not less than for 1 second for anodal energising, make again after the outage another or other above/electrode that the top is provided with atypical biomolecule is a negative pole, other electrode, current electrode and/or remove as anodal excessively electrode and be no less than for 1 second for anodal energising, class this, with above all/there is the electrode of variety classes biomolecule or setting the top one by one as negative pole, other electrode, current electrode and/or remove as anodal excessively electrode and be anodal energising, all be no less than for 1 second each conduction time, helps finish hybridization reaction; Or
Step (c): repeating step (a) or step (b), or intersection carries out step (a) and step (b) helps finish hybridization reaction;
4) relatively by step 2) with step 3) or thereafter/remove behind the unreacting substance detected top/top is equipped with on the electrode of biomolecule/electric current, impedance, electric capacity, signal to noise ratio (S/N ratio), resistance and/or voltage, wherein, reset procedure comprises solvent, solution or the cataphoresis method of adopting; And/or
5) by top/top be equipped with on the electrode of biomolecule/electric current, impedance, electric capacity, signal to noise ratio (S/N ratio), resistance and/or change in voltage or change numerical value and determine material or molecular species and/or quantity in the solution identical with biomolecule.
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| CNA2007100593435A CN101201350A (en) | 2007-08-29 | 2007-08-29 | Biochip system capable of rapidly hybridization and detection of biomolecule with high sensibility and method thereof |
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| CNA2007100593435A CN101201350A (en) | 2007-08-29 | 2007-08-29 | Biochip system capable of rapidly hybridization and detection of biomolecule with high sensibility and method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101975810A (en) * | 2010-11-01 | 2011-02-16 | 福州大学 | High-pass detection electrode of complex sample and preparation method thereof |
| US8507208B2 (en) | 2009-07-23 | 2013-08-13 | University Of Wyoming | Methods and compositions for detection of biological materials using microfluidic devices |
| CN107589254A (en) * | 2016-07-08 | 2018-01-16 | 奈尔公司 | A kind of manufacture method of immunoliposome complex nano-particle biochip and application |
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| US11402376B2 (en) | 2018-03-23 | 2022-08-02 | University Of Wyoming | Methods and devices for detection of biological materials using electric field assisted rapid analyte capture |
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| US8507208B2 (en) | 2009-07-23 | 2013-08-13 | University Of Wyoming | Methods and compositions for detection of biological materials using microfluidic devices |
| CN101975810A (en) * | 2010-11-01 | 2011-02-16 | 福州大学 | High-pass detection electrode of complex sample and preparation method thereof |
| CN101975810B (en) * | 2010-11-01 | 2013-04-17 | 福州大学 | High-pass detection electrode of complex sample and preparation method thereof |
| CN107589254A (en) * | 2016-07-08 | 2018-01-16 | 奈尔公司 | A kind of manufacture method of immunoliposome complex nano-particle biochip and application |
| US11491483B2 (en) | 2018-02-15 | 2022-11-08 | Ohio State Innovation Foundation | Microfluidic devices and methods for high throughput electroporation |
| US11402376B2 (en) | 2018-03-23 | 2022-08-02 | University Of Wyoming | Methods and devices for detection of biological materials using electric field assisted rapid analyte capture |
| CN108344678A (en) * | 2018-04-25 | 2018-07-31 | 北京怡天佳瑞科技有限公司 | A kind of particulate matter detection means and detection method |
| CN108344678B (en) * | 2018-04-25 | 2021-03-26 | 北京怡天佳瑞科技有限公司 | Particulate matter detection device and detection method |
| US11467081B2 (en) | 2018-04-25 | 2022-10-11 | Nanjing Yitian Biotechnology Co., Ltd. | Particle detection device and detection method |
| CN109136087A (en) * | 2018-09-11 | 2019-01-04 | 京东方科技集团股份有限公司 | Separating chips and separation method |
| CN114260038A (en) * | 2022-01-27 | 2022-04-01 | 郭景桓 | Microarray chip, preparation method and application thereof |
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