CN103293191A - Biochemical detection unit and biochemical instrument thereof - Google Patents
Biochemical detection unit and biochemical instrument thereof Download PDFInfo
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- CN103293191A CN103293191A CN2013101832369A CN201310183236A CN103293191A CN 103293191 A CN103293191 A CN 103293191A CN 2013101832369 A CN2013101832369 A CN 2013101832369A CN 201310183236 A CN201310183236 A CN 201310183236A CN 103293191 A CN103293191 A CN 103293191A
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Abstract
The invention relates to a biochemical detection unit used for detecting specimens. The biochemical detection unit comprises a light guide material plate, a receptor and a resistance sensing element. The receptor is specifically adhered to the specimen, so that the light guide material plate is changed by illumination intensity, and the resistance value of the light guide material of the light guide material plate is further changed.
Description
Technical field
The invention relates to a kind of biochemistry detection unit; Particularly, the invention relates to a kind of biochemistry detection unit with light-guide material.
Background technology
Biochip, in a broad sense, refer to that on materials such as glass, silicon chip, plastic cement utilize industrial technologies such as microelectronics, micromechanics to make the product that is applied to biochemical analysis, its effective object can be any separable compound that gets in gene, protein, cell tissue or the environment.The principal feature of biochip technology is that it analyzes confidence level and accuracy height, analysis speed is fast, and employed sample and reagent are few, can obtain the experimental data of globality (parallelization).
The concept of biochip originates from the twentieth century later stage eighties, American-European many research units realize the condensation products---biochip in conjunction with microelectronics, micromechanics, life science and biological message etc., and its development and application will bring a biotechnology revolution for 21st century.On the whole, biochip research still belongs to the initial stage developing stage in the world, but existing many great achievements, as gene wafer (Genechip, DNAchip or Microarray), protein chip (protein chip), microfluid wafer (Microfluidics) and laboratory wafer (Lab-on-a-chip).Wherein comparatively ripe with the development of gene wafer, the biochip of research and development at present or living skill industry indication mostly refers to the gene wafer.
The gene wafer can be divided into two kinds again according to the mode difference of DNA specimen preparation.First kind of light guiding in-situ synthesis (light-directed synthesis) that the photolithography method (photolithography) that is Affymetrix company develops combines with chemical synthesis.Second kind is Stanford university employed contact point sample method, be to utilize in advance synthetic good DNA to be fixed on the glass sheet so that robotic arm is quick, highdensity, the wafer of this high density proper alignment, it is microarray technology (Microarray) for a lot of persons, and this is the most popular present industry just.
The gene microarray technology of " international standard " is with probe (Probe), normally with thousands of or tens thousand of DNA or cDNA, be fixed on the glass carrier surface that the surface chemistry coating was handled with the high density dot matrix, tested sample then is cDNA target nucleic acid (target).Again glass sheet and sample are carried out cross experiment (Hybridization).Because the single-minded characteristic that DNA is complementary for the bifilar helix structure has, just as the character as the slide fastener, the target nucleic acid in the sample can be hybridized the point of the probe that is fixed on the cDNA microarray nucleotide sequence that contains complementation on glass; To remove less than the sample nucleic acid of hybridization through cleaning again, just can note the position of the point of hybridization reaction, carry out cat scanner and analysis by the flag thing on the probe (probe) (for example: fluorescent, radiating matter, ferment colour generation etc.) more afterwards.
Owing to contain on a slice biochip thousands ofly to ten thousand gene sampling point, so color form (pattern) of producing of flag thing needs suitably record and careful comparison, and may change with the reaction time in the color form, therefore.The judgement of the comparison of color and reaction sampling point just becomes very big challenge.In view of this, the inventor is in order to improve and to solve above-mentioned shortcoming, and deep thinking research and cooperate academic theoretical running, and proposes a kind of reasonable in design and effectively improve the present invention of above-mentioned shortcoming.
Summary of the invention
A purpose of the present invention is to provide a kind of biochemistry detection unit, integration by light-guide material and acceptor, and then when a corpse or other object for laboratory examination and chemical testing adheres to acceptor, the illumination of light-guide material plate will be subjected to a corpse or other object for laboratory examination and chemical testing and cover and change, because illumination changes, but the resistance sensing element then resistance value of the light-guide material of sensing photoconduction plate of material changes, and therefore critically a sensing corpse or other object for laboratory examination and chemical testing adheres to special receptor, and the present invention just so can avoid the shortcoming because of color comparison error.
Another object of the present invention is to provide a kind of biochemical instrument of release first affinity agent, characteristic by the first affinity agent reactive end and adhesion end, and make first affinity agent that the acceptor that has adhered to a corpse or other object for laboratory examination and chemical testing can be adhered to single-mindedly, and then avoid pseudo-positive reaction (False Positive Reaction).
Another object of the present invention is to provide a kind of biochemical instrument with quantitative function, setting by sprue, runner and separative element, can suitably a corpse or other object for laboratory examination and chemical testing be scattered in the differential responses zone, produce supersaturation reaction (Oversaturation) to avoid a corpse or other object for laboratory examination and chemical testing to concentrate on some conversion zone especially.
The invention provides a kind of biochemistry detection unit that is used for detecting a corpse or other object for laboratory examination and chemical testing, it comprises light-guide material plate, acceptor and resistance sensing element.Acceptor is arranged on the light-guide material plate, and comprises the affinity end, and it can contain certain distance between affinity end and the light-guide material plate for adhere to a corpse or other object for laboratory examination and chemical testing single-mindedly.In other words, the affinity end directly is not connected with the light-guide material plate.
Resistance sensing element of the present invention, be and the electric coupling of light-guide material plate, therefore can sense factor receptor and adhere to the change of illumination on the light-guide material plate that a corpse or other object for laboratory examination and chemical testing causes, because illumination changes the resistance value that will influence light-guide material and changes, so the resistance sensing element can change for the resistance value of sensing photoconduction plate of material.
Description of drawings
Figure 1A is shown as the synoptic diagram of biochemistry detection unit;
Figure 1B is shown as the synoptic diagram of biochemistry detection unit process;
Fig. 2 A is shown as the reaction synoptic diagram of biochemical instrument;
Fig. 2 B is shown as the synoptic diagram of biochemical instrument reaction embodiment;
Fig. 3 is shown as the synoptic diagram of biochemical instrument reactions change embodiment;
Fig. 4 is shown as the synoptic diagram that biochemical instrument reacts other embodiment;
Fig. 5 A is shown as the synoptic diagram that biochemical instrument is avoided pseudo-positive embodiment;
Fig. 5 B is shown as the synoptic diagram that biochemical instrument is avoided pseudo-positive other embodiment;
Fig. 6 A is shown as the synoptic diagram that covers embodiment of biochemistry detection unit;
Fig. 6 B is shown as the synoptic diagram that covers alternate embodiment of biochemistry detection unit;
Fig. 7 A is shown as the synoptic diagram of biochip;
Fig. 7 B is shown as the synoptic diagram of biochip Z axle embodiment one;
Fig. 7 C is shown as the synoptic diagram of biochip Z axle embodiment two;
Fig. 7 D is shown as the synoptic diagram of biochip Z axle embodiment three;
Fig. 7 E is shown as the synoptic diagram of biochip X-Y axle embodiment one;
Fig. 7 F is shown as the synoptic diagram of biochip X-Y axle embodiment two;
Fig. 8 is shown as the synoptic diagram of biochemistry detection unit variable color embodiment;
Fig. 9 A is the synoptic diagram of biochemical instrument separative element embodiment one;
Fig. 9 B is the synoptic diagram of biochemical instrument separative element embodiment two;
Fig. 9 C is the synoptic diagram of biochemical instrument separative element embodiment three.
The main element symbol description
1 biochemistry detection unit, 60 releasing units
15 reaction compartments, 601 first accommodation spaces
17 closing lids, 603 second accommodation spaces
2 biochemical instruments 605 the 3rd accommodation space
20 corpse or other object for laboratory examination and chemical testing, 70 first affinity agents
21 epi-positions 701 are sticked end, first and are sticked end
26 sprues, 702 reactive end
261 openings, 702 ' fluorescent reactive end, the reaction of first fluorescent
27 runner ends
28 separative elements, 704 ferment
30 light-guide material plates, 71 second affinity agents
35 reactants 711 second stick end
40 resistance sensing elements, 712 second fluorescent reactive end
41 resistance change signal 80 luminescence-producing reaction agent
50 receptor 9s, 0 outer light source
The fluorescent of 51 affinity end x, first wavelength coverage
The fluorescent of 511 shielded area y, second wavelength coverage
52 abutting ends
Embodiment
The corpse or other object for laboratory examination and chemical testing that biochemistry detection of the present invention unit can be used to detect comprises Amino acid monomer, Amino acid fragment, Amino acid polymkeric substance, protein, organic compound, mineral compound, metallic compound (comprising oxide, sulfide, nitro compound), metal alloy, organic polymer monomer and various organic polymer.
Among the embodiment shown in Figure 1A, the present invention is used for detecting the biochemistry detection unit 1 of a corpse or other object for laboratory examination and chemical testing 20, and it comprises light-guide material plate 30, acceptor 50 and resistance sensing element 40.Acceptor 50 shown in Figure 1A, preferable being arranged on the light-guide material plate 30, acceptor 50 is preferably immunoglobulin (Ig), yet in other embodiments, acceptor 50 also can be other Amino acid fragments, as has the Amino acid fragment that selectivity adheres to a corpse or other object for laboratory examination and chemical testing 20.Among the embodiment shown in Figure 1A, acceptor 50 comprises affinity end 51 and abutting end 52, affinity end 51 can be for adhere to a corpse or other object for laboratory examination and chemical testing 20 single-mindedly, and " adhering to " of this place speech refers to that the affinity that affinity end 51 Amino acid fragments can be passed through between hydrogen bond, Fan Dewali equimolecular and the molecule adheres to single-mindedly.Among the embodiment shown in Figure 1A, abutting end 52 is preferably the Fc zone of immunoglobulin (Ig), and the mode that abutting end 52 is preferably with chemical bonded refractory is connected in light-guide material plate 30; Yet in other embodiment (not shown), the annexation between abutting end 52 and the light-guide material plate 30 also can be connected with affinity between the molecule by hydrogen bond, Fan Dewali equimolecular.Therefore, contain distance between affinity end 51 and the light-guide material plate 30, this distance is variant with size with the structure of factor receptor 50, and distance is preferably between the 0.1 μ m to 0.1cm, is more preferred between the 1 μ m to 1mm, between 10 μ m to the 100 μ m.
Shown in the embodiment of Figure 1A, biochemistry detection unit 1 comprises resistance sensing element 40, and resistance sensing element 40 and 30 electric coupling of light-guide material plate are for the resistance value change of sensing light-guide material 30.Resistance sensing element 40 is preferably avometer or other can be for instrument or the device of measured resistance value change.
Among the embodiment as shown in Figure 1B, acceptor 50 can be designed to have the affinity that adheres to a corpse or other object for laboratory examination and chemical testing 20 single-mindedly, acceptor 50 can design because affinity adheres to a corpse or other object for laboratory examination and chemical testing 20 and produce structural change (conformational change) this moment, and weaken affinity between abutting end 52 and the light-guide material plate 30, because affinity weakens and will abutting end 52 be separated easily with light-guide material plate 30, when treating that acceptor 50 together separates with light-guide material plate 30 with a corpse or other object for laboratory examination and chemical testing 20, light-guide material plate 30 increases because of light-receiving area, thereby allows the resistance value of resistance sensing element 40 sensing light-guide materials 30 change.Herein resistance value changes can comply with different light-guide materials 30, is designed to descend or rise because illuminance increases the resistance value that causes different light-guide materials, and then makes the resistance sensing element 40 change signal 41 that has a resistance.In other words, resistance changes signal 41 and refers to the change of resistance value, but not singly refers to decline or the rising of resistance value.
Light-guide material of the present invention (photoconductor) is defined as the material that can be converted into electromagnetic radiation electric current, and electromagnetic radiation is often referred to ultraviolet light, visible light and infrared light.In general behind this class material static electrification, be subjected to the illumination of special wavelength to penetrate the back and just static can be changed into electric current.In other words, these materials must be good insulating bodies darkling, are subjected to become good conductor at once behind the light.The light-guide material of light-guide material plate 30 of the present invention mainly can be divided into organic light-guide material and inorganic light-guide material.Organic light-guide material be selected from polyvinylcarbazole, phthalocyanine complex, azo-compound, this overstates the potpourri of quinoline compound and above-mentioned substance.And inorganic light-guide material is the potpourri that is selected from selenium, selen-tellurjum alloy, cadmium sulfide, zinc paste, vulcanized lead, indium antimonide and above-mentioned substance.Light-guide material plate 30 of the present invention can be made of the light-guide material that pure organic light-guide material, pure inorganic light-guide material or organic-inorganic mix.In addition, the hybrid mode of organic-inorganic hybrid lightguide material is including but not limited to modes such as stacking, mixed crystallization, coating and chemical vapor depositions.
Among the embodiment shown in Fig. 2 A, use the biochemical instrument 2 preferable releasing units 60 that comprise of biochemistry detection unit.In this embodiment, releasing unit 60 comprises first accommodation space 601 and second accommodation space 603, releasing unit 60 is not limited to only comprise two accommodation spaces, also can only comprise an accommodation space or more than one accommodation space, when for example only containing an accommodation space, single accommodation space gets final product ccontaining different material for reaction.In this embodiment, releasing unit 60 is preferably controllable reagent input media, this installs available biochemical instrument 2 built-in wafers and controls the accommodation space that it comprises, the concrete mode of control is opened the time of accommodation space, the mode of release accommodation space content as control, and the order of opening each accommodation space respectively.Among the embodiment shown in Fig. 2 A, 603 ccontaining luminescence-producing reaction agent 80 of first accommodation space, 601 ccontaining first affinity agent, 70, the second accommodation spaces.First affinity agent 70 comprises and sticks end 701 and reactive end 702.In preferred embodiment, first affinity agent 70 is to be another strain antibody, and this antibody adheres to the antibody of acceptor 50 single-mindedly than Canon.Yet in other embodiments, first affinity agent 70 must not be antibody, also can be the Amino acid sequence or the protein that have the selectivity affinity with acceptor 50.In this embodiment, accommodation space is preferably the cavity that the reagent input media includes; Yet in other embodiment (not shown), releasing unit 60 is for can controlling the capsule of release time, and first accommodation space 601 and second accommodation space 603 can be respectively the tiny capsules with identical or different dissolution time that comprises in releasing unit 60 large capsules.In the embodiment of this capsule, releasing unit 60 also has same above-mentioned control mode, and control concrete mode and open the time of accommodation space, the mode of release accommodation space content as control, and the order of opening each accommodation space respectively.
Shown in the embodiment of Fig. 2 A, sticking of first affinity agent 70 holds 701 can adhere to the affinity end 51 that adheres to a corpse or other object for laboratory examination and chemical testing 20 single-mindedly.Therefore first affinity agent 70 can be avoided and acceptor 50, because of non-narrow spectrum combination, and the light-guide material resistance value of biochemistry detection of the present invention unit 1 sensing photoconduction plate of material 30 is changed, and then pseudo-positive (False Positive) reaction when avoiding observational measurement.In addition, non-narrow spectrum in conjunction with producing pseudo-positive reaction with acceptor 50 for fear of first affinity agent 70, shown in the embodiment of Fig. 2 B, luminescence-producing reaction agent 80 is (as 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) or 3,3 ', 5,5 '-Tetramethyl benzidine) can with ferment 704 (as the peroxidase peroxidase) reaction of reactive end 702 ends of first affinity agent 70 after send the fluorescent of particular range of wavelengths, this reaction also is called ferment immunoassay (ELISA).In this embodiment, the wavelength coverage sent of fluorescent is preferably and is selected from 620～750nm, 495～570nm and 358～461nm; Yet in other embodiments, the best is to be selected from 575～900nm, 470～610nm, 300～480nm.After above-mentioned fluorescent exposes to light-guide material plate 30, cooperate suitable light-guide material and resistance sensing element 40, can change signal 41 by resistance and detect the affinity end 51 that a corpse or other object for laboratory examination and chemical testing 20 adheres to acceptor 50 really.In other words, behind a corpse or other object for laboratory examination and chemical testing 20 adhesion receptors 50, the fluorescent by luminescence-producing reaction agent 80 and ferment 704 reactions are sent can excite photoconduction plate of material 30 and the resistance value of change light-guide material.Because a corpse or other object for laboratory examination and chemical testing 20 generally is entrained by fluid, the scope of fluid is including but not limited to air, liquid and semisolid (colloid).Because fluid except a corpse or other object for laboratory examination and chemical testing 20 being carried into acceptor 50, also can not carried outside there being first affinity agent 70 that adheres to.
Among the embodiment as shown in Figure 3, the biochemical instrument 2 of using the biochemistry detection unit further comprises releasing unit 60, and the releasing unit 60 of this embodiment comprises first accommodation space 601, is single accommodation space in this embodiment.First accommodation space, 601 ccontaining first affinity agents 70, releasing unit 60 can be controlled first accommodation space 601 and discharge at least one first affinity agent, 70, the first affinity agents 70 and comprise and stick end 701 and reactive end 702.In this embodiment, adhere to end 701 and adhere to the affinity end 51 that adheres to a corpse or other object for laboratory examination and chemical testing 20.It is different with previous embodiment that to be in, the reactive end 702 that first affinity agent 70 comprises be from the light wave that sends particular range of wavelengths.Particularly, this principle is radiommunoassay (radioimmunoassay).In this embodiment, reactive end 702 be preferably with merge isotope (as
12C,
14C,
131I) Amino acid is the unit; Yet in other embodiments, adhere to end 701 also can be designed to adhere to specific isotope (as
12C,
14C,
131I) Amino acid sequence, so reactive end 702 is the isotope material at this moment.In this embodiment, if reactive end 702 is when be isotope, its oneself light wave of sending including but not limited to α, β or gamma-rays.In other embodiments, reactive end 702 also can be self luminous fluorescent albumen, and in this embodiment, the particular range of wavelengths that reactive end 702 is sent is preferably and is selected from 620～750nm, 495～570nm and 358～461nm; Yet in other embodiments, the best is to be selected from 575～900nm, 470～610nm, 300～480nm.Among the embodiment as shown in Figure 3, when 702 of reactive end from the x radiation xs that send during to light-guide material plate 30, resistance sensing element 40 can be responded to light-guide material and excited by ray and the resistance value that changes, and then the change signal 41 that has a resistance.
Among the embodiment as shown in Figure 4, the biochemical instrument 2 of using the biochemistry detection unit further comprises releasing unit 60 and outer light source 90, and releasing unit 60 disengages at least one first affinity agent, 70, the first affinity agents 70 and comprises to stick and hold 701 and fluorescent reactive end 702 '.Stick end 701 and adhere to the affinity end 51 that adheres to a corpse or other object for laboratory examination and chemical testing 20.Different with previous embodiment be in, after fluorescent reactive end 702 ' was subjected to outer light source 90 illumination, fluorescent reactive end 702 ' can be sent the fluorescent of particular range of wavelengths, this fluorescent can excite photoconduction plate of material 30 and change the resistance value of light-guide material plate 30.In this embodiment, outer light source 90 is including but not limited to radium-shine, white light and other monochromatic source.In addition, fluorescent reactive end 702 ' can be designed to send the fluorescent albumen (as green fluorescent Protein G FP, red fluorescent albumen HcRed, yellow fluorescent albumen ZsYellow etc.) of different wavelength range, and the particular range of wavelengths of the fluorescent reactive end 702 ' light wave that sends is preferably and is selected from 620～750nm, 495～570nm and 358～461nm; Yet in other embodiments, the best is to be selected from 575～900nm, 470～610nm, 300～480nm.By the light-guide material that collocation design is fit to, light-guide material plate 30 can be excited by fluorescent and change resistance value, so resistance sensing element 40 can be responded to and the change signal 41 that has a resistance.
In qualitative analysis, pseudo-positive reaction regular meeting causes the erroneous judgement of testing result, in order to reduce the generation of pseudo-positive reaction.Shown in the embodiment of Fig. 5 A, the releasing unit 60 of using the biochemical instrument 2 of biochemistry detection unit comprises first accommodation space 601 and second accommodation space 603.First accommodation space, 601 ccontaining first affinity agent, 70, the first affinity agents 70 comprise first and stick the end 701 and first fluorescent reactive end 702 '.Second accommodation space, 603 ccontaining second affinity agent, 71, the second affinity agents 71 comprise second and stick the end 711 and second fluorescent reactive end 712.First adheres to the affinity end 51, the second that adheres to a corpse or other object for laboratory examination and chemical testing 20 with sticking end 701 selectivitys sticks adhesion shielded area 511, end 711 selectivitys ground, and shielded area 511 is defined as acceptor 50 parts that cover when a corpse or other object for laboratory examination and chemical testing 20 adheres to affinity ends 51.In this embodiment, the biochemical instrument 2 of using the biochemistry detection unit comprises outer light source 90 in addition, and the light wavelength scope that outer light source 90 sends as previously mentioned.After second affinity agent 71 sticks shielded area 511, when being subjected to light that outer light source 90 sends and exposing to the second fluorescent reactive end 712, the second fluorescent reactive end 712 will exhale the fluorescent x of first wavelength coverage, because in the adjacent biochemistry detection unit 1, first of first affinity agent 70 stick the end 701 adhere to the affinity end 51 that adheres to a corpse or other object for laboratory examination and chemical testing 20 after, be connected in fluorescent reactive end 702 ' because first adheres to end 701, after the fluorescent x that this fluorescent reactive end 702 ' is subjected to first wavelength coverage excites, the fluorescent y of second wavelength coverage will be sent, and then excite the photoconduction material and change the resistance value of light-guide material plate 30, thereby have a resistance and change signal 41.Change signal 41 because adjacent two biochemistry detection unit 1 have only one of them to have a resistance, therefore can get rid of the pseudo-positive reaction that all there is the change signal 41 that has a resistance adjacent two biochemistry detection unit 1 by this.Because understanding, the affinity end 51 of acceptor 50 and the distance of light-guide material plate 30 influence the illumination that the second wavelength coverage fluorescent y shines the light-guide material plate 30 that is connected in second affinity agent 71.Therefore under faint illumination, the biochemistry detection unit 1 that second affinity agent 71 engages can't have a resistance and change signal 41; In addition, in other embodiment (not shown), also can the polaroid that can filter the second wavelength coverage fluorescent y be set between adjacent biochemistry detection unit 1, make the fluorescent y of second wavelength coverage can only in the biochemistry detection unit 1 that first affinity agent 70 engages, produce reaction.In this design, can get rid of the pseudo-positive reaction that all there is the change signal 41 that has a resistance adjacent two biochemistry detection unit 1.In this embodiment, the fluorescent of first wavelength coverage and second wavelength coverage is preferably and is selected from 620～750nm, 495～570nm and 358～461nm; Yet in other embodiments, the best is to be selected from 575～900nm, 470～610nm, 300～480nm, but first wavelength coverage is not overlapped in second wavelength coverage.For example, if when first wavelength coverage of fluorescent x is 620～750nm, second wavelength coverage of fluorescent y then can be designed to 495～570nm or 358～461nm.
In the alternate embodiment shown in Fig. 5 B, the releasing unit 60 of using the biochemical instrument 2 of biochemistry detection unit comprises first accommodation space 601, second accommodation space 603 and the 3rd accommodation space 605.First accommodation space 601 comprises first affinity agent, 70, the second accommodation spaces, 603 ccontaining second affinity agents 71, and the 3rd accommodation space 605 comprises at least one luminescence-producing reaction agent 80.When first affinity agent 70 and second affinity agent 71, after adhering to biochemistry detection unit 1 among the embodiment as described above, releasing unit 60 discharge that at least one luminescence-producing reaction agent 80 will be spread gradually and with 712 effects of the second fluorescent reactive end after, send the fluorescent x of first wavelength coverage, and the first wavelength coverage fluorescent x can further excite the first fluorescent reactive end 702 ' and send the fluorescent y of second wavelength coverage.In this embodiment, can get rid of adjacent two biochemistry detection unit 1 all has the pseudo-positive reaction of the change signal 41 that has a resistance, but this embodiment is the source that provides fluorescent to excite mutually with luminescence-producing reaction agent 80, and the source that the mode of light source 90 provides fluorescent to excite mutually not.In the alternate embodiment shown in Fig. 5 B, the fluorescent of first wavelength coverage and second wavelength coverage is preferably and is selected from 620～750nm, 495～570nm and 358～461nm; Yet in other embodiments, the best is to be selected from 575～900nm, 470～610nm, 300～480nm, but first wavelength coverage is not overlapped in second wavelength coverage.
Among the embodiment as shown in Figure 6A, a kind of biochemistry detection unit 1 that is used for detecting a corpse or other object for laboratory examination and chemical testing 20 comprises outer light source 90, light-guide material plate 30, acceptor 50 and resistance sensing element 40.Outer light source 90 shines in acceptor 50, light-guide material plate 30, in this embodiment, the affinity end 51 of acceptor 50 can adhere to a bigger corpse or other object for laboratory examination and chemical testing 20, because a corpse or other object for laboratory examination and chemical testing 20 is too big or have a bigger area coverage, so that light subject 20 covers and produces capture-effect, make light-guide material plate 30 not have to have a resistance because of the irradiation that does not receive light and change signal 41.Shown in the embodiment of Fig. 6 B, a corpse or other object for laboratory examination and chemical testing 20 epi-positions (epitope) difference that 51 at the affinity end of the acceptor 50 of adjacent biochemistry detection unit 1 can adhere to, but because a large-scale corpse or other object for laboratory examination and chemical testing 20 has different epi-position 21, therefore if design in the time of to adhere to the adjacent biochemistry detection unit 1 of a large-scale corpse or other object for laboratory examination and chemical testing 20 different epi-positions 21, the light of outer light source 90 will produce capture-effect because of a large-scale corpse or other object for laboratory examination and chemical testing 20, and then reduce Fig. 6 A embodiment and adhere to the non-selectivity capture-effect that other a non-corpse or other object for laboratory examination and chemical testing 20 materials produce because of non-selectivity, and then reduce pseudo-negative (False Negative) reaction.
Biochemistry detection of the present invention unit 1 is namely as above-mentioned light-guide material plate 30, acceptor 50 and the resistance sensing element 40 of comprising.By assembling many biochemistry detection unit 1, can form and detect wafer or be referred to as biochip.Preferable in the biochip have 106 to 1012 biochemistry detection unit 1, yet in other different design wafers, the quantity of biochemistry detection unit 1 is not as limit.In the preferred embodiment of biochip, the design of biochemistry detection unit 1 is not identical.For example, the embodiment shown in Fig. 6 B, adjacent biochemistry detection unit 1 is just inequality.Because biochip shown in the embodiment of Fig. 7 A, comprises a plurality of biochemistry detection unit 1.In addition, shown in Fig. 7 B, if with the Z axle, each biochemistry detection unit 1 from top to bottom can be docile and obedient order and be arranged, then having reaction compartment 15 between every row biochemistry detection unit 1 can be for the fluid that carries a corpse or other object for laboratory examination and chemical testing 20, fluid comprises air, liquid and semisolid (colloid), and when fluid is transported to 1 place, biochemistry detection unit with a corpse or other object for laboratory examination and chemical testing 20, acceptor 50 will stick according to selectivity affinity and a corpse or other object for laboratory examination and chemical testing 20.Among the embodiment shown in Fig. 7 C and Fig. 7 D, the arrangement mode of biochemistry detection unit 1 also can have other modes, and the alternating expression shown in Fig. 7 C is arranged.Alternating expression is arranged the unit reaction compartment 15 that can increase biochemistry detection unit 1, also can avoid biochemistry detection unit 1 too approaching simultaneously, to such an extent as to produce pseudo-positive reaction as far as possible.Closed type shown in Fig. 7 D is arranged the volume that can reduce biochip, be easy to be convenient for carrying, because each biochemistry detection unit 1 is too approaching, therefore need the setting of closing lid 17, the closing lid 17 preferable tops that are arranged at every row biochemistry detection unit 1 are with the pseudo-positive reaction that prevents that the fluorescent scattering from being produced.In addition, closed type is arranged the unit's of causing reaction compartment 15 is reduced, therefore for the fluid that contains a large amount of corpse or other object for laboratory examination and chemical testing 20 or just more suitable than sensitive biochemistry detection unit 1.This is owing under the constant prerequisite of a corpse or other object for laboratory examination and chemical testing 20 quantity in the per unit fluid, and unit reaction compartment 15 reduces, and biochemistry detection unit 1 then reduces with the collision probability of a corpse or other object for laboratory examination and chemical testing 20, in order to produce suitable detecting result, then needs to increase the quantity of a corpse or other object for laboratory examination and chemical testing 20 in the per unit fluid.
In addition, shown in the embodiment of Fig. 7 E and Fig. 7 F, the arrangement of biochemistry detection unit 1, with the X-Y axle, light-guide material plate 30 is uninevitable shown in Fig. 7 F, constituted and arranged by the light-guide material plate 30 of identical material, shown in the embodiment of Fig. 7 E, also can be arranged alternately by the light-guide material plate 30 of different light-guide material.The pseudo-positive reaction that different mutual arrangement mode shown in Fig. 7 E produces in the time of can further avoiding the fluorescent scattering.This is because the fluorescent frequency of scattering can not excite different light-guide material plates 30, and the scattering fluorescent is for the illumination difference of every light-guide material plate 30, even light-guide material plate 30 too far away can be excited by this fluorescent frequency, but because the illumination deficiency also can't make resistance sensing element 40 produce induction.
As shown in Figure 8, the biochemistry detection unit 1 that is used for detecting a corpse or other object for laboratory examination and chemical testing 20 comprises outer light source 90, light-guide material plate 30, reactant 35 and resistance sensing element 40.Reactant 35 is to be arranged on the light-guide material plate 30, when treating a corpse or other object for laboratory examination and chemical testing 20 contact reaction agent 35,35 of reactants can produce chemical change and variable color, because the reactant 35 after the variable color can influence the light illumination that outer light source 90 throws, therefore will weaken outer light source and shine in the illumination of light-guide material plate 30.Because illumination changes, resistance sensing element 40 mats and 30 electric coupling of light-guide material plate and the change signal 41 that has a resistance.In an embodiment, because reactant 35 directly is arranged on the light-guide material plate 30, therefore reactant 35 also can be considered a kind of acceptor 50, though reactant 35 generally has selectivity for a corpse or other object for laboratory examination and chemical testing 20 in this embodiment, but in other embodiments, reactant 35 but has reactivity for a corpse or other object for laboratory examination and chemical testing 20 but must not have selectivity.This is because reactant 35 can be designed to and specific compound reaction, or is designed to and the particular functional radical reaction, so reactant 35 can detect the simplification compound, also can detect specific derivatives.
Among the embodiment shown in Fig. 9 A, the biochemical instrument 2 of using the biochemistry detection unit further comprises sprue 26, at least one runner 27 and separative element 28.Runner 27 is communicated with sprue 26 in opening 261.In this embodiment, light-guide material plate 30 is arranged at the end of runner 27; Yet in other embodiment (not shown), light-guide material plate 30 is arranged in runner 27 or the sprue 26.Because biochemical instrument 2 has separative element 28 and is arranged at opening 261, selectively allows a corpse or other object for laboratory examination and chemical testing 20 to enter runner 26.Therefore, if the excessive concentration of a corpse or other object for laboratory examination and chemical testing 20 and may cause supersaturation the time, separative element 28 selectively makes a corpse or other object for laboratory examination and chemical testing 20 can't enter runner 26, therefore a corpse or other object for laboratory examination and chemical testing 20 can't produce supersaturation with 1 reaction of biochemistry detection unit, analyzes quantitative effect and the biochemical instrument 2 of using the biochemistry detection unit can be reached.Among the embodiment shown in Fig. 9 A, separative element 28 is valve, valve 28 electric signals connect resistance sensing element 40, when the adhesive reaction of the biochemistry detection unit 1 of runner 27 ends and a corpse or other object for laboratory examination and chemical testing 20 or metachromasia have been tending towards saturated, when resistance sensing element 40 changes the sensing resistor value above predetermined value, resistance sensing element 40 will be exported the control signal to valve 28, make valve 28 close opening 261.Therefore, the design of valve 28 of the present invention can avoid a corpse or other object for laboratory examination and chemical testing 20 and biochemistry detection unit 1 to produce oversaturated reaction, thereby the quantitative effect of analysis of attainable cost invention.
Among the embodiment shown in Fig. 9 B, the biochemical instrument 2 of using the biochemistry detection unit comprises sprue 26 and a plurality of runner 27 as N
1, N
2N
nEach runner 27 is opening 261 with the junction of sprue 26, in this embodiment, be positioned at the preferable separative element 28 that arranges in opening 261 places, separative element 28 can be the electrode group, electrode group 28 will produce dielectrophoretic force (dielectrophoretic force), the dielectrophoretic force that is produced by electrode group 28 can use and screen a suitable corpse or other object for laboratory examination and chemical testing 20 and enter runner 27, therefore dielectrophoretic force selectively allows a corpse or other object for laboratory examination and chemical testing 20 to enter runner 27, and arrive runner 27 terminal and with 1 reaction of biochemistry detection unit.Yet in other embodiments, separative element 28 also can be optics folder (optical tweezer), and optics folder 28 separates different corpse or other object for laboratory examination and chemical testing 20.The present invention can be apt to the technical approach with optics folder 28, optionally allows a corpse or other object for laboratory examination and chemical testing 20 to enter runner 27, and then avoids a corpse or other object for laboratory examination and chemical testing 20 and the supersaturation of biochemistry detection unit 1 to react.
Among the embodiment shown in Fig. 9 C, use and to be connected to opening 261 between the sprue 26 of biochemical instrument 2 of biochemistry detection unit and the runner 27.In this embodiment, separative element 28 is for being arranged at the semi-permeable diaphragm at opening 261 places, semi-permeable diaphragm 28 is the corpse or other object for laboratory examination and chemical testing 20 of penetrating different sizes optionally, and can be because the concentration of an osmotic pressure influence corpse or other object for laboratory examination and chemical testing 20 in runner 27 of a corpse or other object for laboratory examination and chemical testing 20, therefore a corpse or other object for laboratory examination and chemical testing 20 concentration in the runner 27 will be reached certain balance, and be unlikely to make a corpse or other object for laboratory examination and chemical testing 20 and biochemistry detection unit 1 to produce the supersaturation reaction.And the quantitative effect of analysis of attainable cost invention.
The present invention is described by above-mentioned related embodiment, yet above-described embodiment is only for implementing example of the present invention.Must be pointed out that the embodiment that has disclosed does not limit the scope of the invention.On the contrary, being contained in the modification of the spirit of claim and scope and equalization arranges and all is contained in the scope of the present invention.
Claims (4)
1. biochemistry detection unit that is used for detecting a corpse or other object for laboratory examination and chemical testing comprises:
One outer light source;
One light-guide material plate, this outer light source shine in this light-guide material plate;
One reactant is arranged on this light-guide material plate, when treating that this corpse or other object for laboratory examination and chemical testing contacts this reactant, and this reactant variable color and weaken this outer light source and shine in the illumination of this light-guide material plate; And
One resistance sensing element, with this light-guide material plate electric coupling, the resistance value that produces because this light-guide material plate illumination changes for sensing changes.
2. an application further comprises as asking the biochemical instrument of 1 a described biochemistry detection unit:
One sprue;
At least one runner is communicated with this sprue in an opening, and this light-guide material plate is arranged at this sprue or this runner; And
One separative element is arranged at this opening, selectively allows this corpse or other object for laboratory examination and chemical testing to enter this runner.
3. as request 2 a described biochemical instrument, wherein this separative element comprises a semi-permeable diaphragm.
4. as request 2 a described biochemical instrument, wherein this separative element comprises a valve, this valve electric signal connects this resistance sensing element, when this resistance value of this resistance sensing element sensing changes above predetermined value, this resistance sensing element output one is controlled signal to this valve, this opening of this valve closing.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010101384937A CN102192902B (en) | 2010-03-19 | 2010-03-19 | Biochemical detection unit and biochemical apparatus thereof |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2010101384937A Division CN102192902B (en) | 2010-03-19 | 2010-03-19 | Biochemical detection unit and biochemical apparatus thereof |
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| CN103293191A true CN103293191A (en) | 2013-09-11 |
| CN103293191B CN103293191B (en) | 2015-07-29 |
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| CN201310183236.9A Expired - Fee Related CN103293191B (en) | 2010-03-19 | 2010-03-19 | Biochemistry detection unit and biochemical instrument thereof |
| CN2010101384937A Expired - Fee Related CN102192902B (en) | 2010-03-19 | 2010-03-19 | Biochemical detection unit and biochemical apparatus thereof |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4334880A (en) * | 1980-10-20 | 1982-06-15 | Malmros Mark K | Analytical device having semiconductive polyacetylene element associated with analyte-binding substance |
| CN2363281Y (en) * | 1998-08-26 | 2000-02-09 | 中国科学院南京地理与湖泊研究所 | Carbonate content automatic analyzer |
| CN1515898A (en) * | 2003-01-08 | 2004-07-28 | 力捷电脑股份有限公司 | Biological chip capable of raising measurement reliability and its method |
| US20060205060A1 (en) * | 2005-01-11 | 2006-09-14 | Young-Il Kim | Biosensor, biosensor system and method of using thereof |
| CN101152650A (en) * | 2006-09-25 | 2008-04-02 | 明基电通股份有限公司 | Fluid fine particle separating device |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3547599B2 (en) * | 1997-12-10 | 2004-07-28 | 独立行政法人 科学技術振興機構 | Gene sensor |
| DE102005018337A1 (en) * | 2005-04-20 | 2006-11-02 | Micronas Gmbh | Micro-optical detection system and method for determining temperature-dependent parameters of analytes |
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2010
- 2010-03-19 CN CN201310183236.9A patent/CN103293191B/en not_active Expired - Fee Related
- 2010-03-19 CN CN2010101384937A patent/CN102192902B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4334880A (en) * | 1980-10-20 | 1982-06-15 | Malmros Mark K | Analytical device having semiconductive polyacetylene element associated with analyte-binding substance |
| CN2363281Y (en) * | 1998-08-26 | 2000-02-09 | 中国科学院南京地理与湖泊研究所 | Carbonate content automatic analyzer |
| CN1515898A (en) * | 2003-01-08 | 2004-07-28 | 力捷电脑股份有限公司 | Biological chip capable of raising measurement reliability and its method |
| US20060205060A1 (en) * | 2005-01-11 | 2006-09-14 | Young-Il Kim | Biosensor, biosensor system and method of using thereof |
| CN101152650A (en) * | 2006-09-25 | 2008-04-02 | 明基电通股份有限公司 | Fluid fine particle separating device |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102192902A (en) | 2011-09-21 |
| CN103293191B (en) | 2015-07-29 |
| CN102192902B (en) | 2013-12-11 |
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