CN103293191B - Biochemistry detection unit and biochemical instrument thereof - Google Patents
Biochemistry detection unit and biochemical instrument thereof Download PDFInfo
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- CN103293191B CN103293191B CN201310183236.9A CN201310183236A CN103293191B CN 103293191 B CN103293191 B CN 103293191B CN 201310183236 A CN201310183236 A CN 201310183236A CN 103293191 B CN103293191 B CN 103293191B
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Abstract
The invention relates to a kind of biochemistry detection unit being 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 adheres to a corpse or other object for laboratory examination and chemical testing in specific manner and causes light-guide material plate to change by illuminance, and then causes the resistance value of the light-guide material of light-guide material plate to change.
Description
Technical field
The invention relates to a kind of biochemistry detection unit; Specifically, the invention relates to a kind of biochemistry detection unit with light-guide material.
Background technology
Biochip, in a broad sense, refer in the materials such as glass, silicon chip, plastic cement, utilize the industrial technology such as microelectronics, micromechanics to make the product being applied to biochemical analysis, its effective object can be the separable and compound obtained any in gene, protein, cell tissue or environment.The principal feature of biochip technology is that it analyzes confidence level and accuracy is high, analysis speed fast, the sample used and reagent few, the experimental data of globality (parallelization) can be obtained.
The concept of biochip originates from the twentieth century later stage eighties, American-European many research units realize condensation products---the biochip in conjunction with microelectronics, micromechanics, life science and bioinformatics etc., and its development and application will bring a Biotechnology for 21st century.On the whole, biochip research still belongs to 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 lab cards (Lab-on-a-chip).Wherein comparatively ripe with gene wafers progress, the biochip of current research and development or raw skill industry indication mostly refers to gene wafer.
The mode difference that gene wafer is prepared according to DNA sample can be divided into two kinds again.The light that the first optical lithography (photolithography) being Affymetrix company develops combines with chemical synthesis guides in-situ synthesis (light-directed synthesis).The second is the contact point sample method that Stanford university uses, utilize that pre-synthesis DNA is quick with robotic arm, highdensity to be fixed on glass sheet, the wafer of this high density proper alignment, a lot of person it be microarray technology (Microarray), this industry at present the most popular just.
The gene microarray technology of " international standard " is by probe (Probe), normally by thousands of or tens thousand of DNA or cDNA, be fixed on high density dot matrix and be coated with the glass carrier that processed on the surface through surface chemistry, tested sample is then cDNA target nucleic acid (target).Again glass sheet and sample are carried out cross experiment (Hybridization).Because DNA is that the double helix model has complementary single-minded characteristic, just as the character as slide fastener, the target nucleic acid in sample, can hybridize the point of the probe be fixed on containing complementary nucleotide sequence on cDNA microarray glass; Remove there is no the sample nucleic acid of hybridizing through cleaning again, just can record the position of the point of hybridization reaction, carry out cat scanner and analysis by the flag thing (such as: fluorescent, radiating matter, ferment colour generation etc.) on probe (probe) more afterwards.
Due on a slice biochip containing thousands of to ten thousand gene sampling point, the therefore colored forms (pattern) that produces of flag thing, needs suitably to record and carefully comparison, and may change with the reaction time in colored forms, therefore.The comparison of color and the judgement of reaction sampling point just become very large challenge.In view of this, the present inventor is in order to improve and solve above-mentioned shortcoming, and deep thinking is studied and coordinate the running of academic theory, and proposes a kind of reasonable in design and effectively improve the present invention of above-mentioned shortcoming.
Summary of the invention
An object of the present invention is to provide a kind of biochemistry detection unit, by the integration of 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 subject to a corpse or other object for laboratory examination and chemical testing and covers and change, because illumination changes, the resistance value that resistance sensing element then can sense the light-guide material of photoconduction plate of material changes, and therefore can critically sense a corpse or other object for laboratory examination and chemical testing and adhere to special receptor, just so the present invention can avoid the shortcoming because of color comparison error.
Another object of the present invention is to the biochemical instrument that a kind of release the first affinity agent is provided, by the first affinity agent reactive end and the characteristic adhering to end, and make the first affinity agent exclusively can adhere to the acceptor adhering to a corpse or other object for laboratory examination and chemical testing, 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, by the setting of sprue, runner and separative element, suitably a corpse or other object for laboratory examination and chemical testing can be scattered in differential responses region, 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 being 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 light-guide material plate, and comprises affinity end, and it for exclusively adhering to a corpse or other object for laboratory examination and chemical testing, can contain certain distance between affinity end and light-guide material plate.In other words, affinity end is not directly connected with light-guide material plate.
Resistance sensing element of the present invention, be and the electric coupling of light-guide material plate, therefore the change that factor receptor adheres to illumination on the light-guide material plate that causes of a corpse or other object for laboratory examination and chemical testing can be sensed, the resistance value affecting light-guide material changed because illumination changes, therefore resistance sensing element can change for the resistance value of sensing photoconduction plate of material.
Accompanying drawing explanation
Figure 1A is shown as the schematic diagram of biochemistry detection unit;
Figure 1B is shown as the schematic diagram of biochemistry detection unit process;
Fig. 2 A is shown as the reaction schematic diagram of biochemical instrument;
Fig. 2 B is shown as the schematic diagram of biochemical instrument reaction embodiment;
Fig. 3 is shown as the schematic diagram of biochemical instrument reactions change embodiment;
Fig. 4 is shown as the schematic diagram that biochemical instrument reacts other embodiment;
Fig. 5 A is shown as the schematic diagram that biochemical instrument avoids pseudo-positive embodiment;
Fig. 5 B is shown as the schematic diagram that biochemical instrument avoids pseudo-other embodiment positive;
Fig. 6 A is shown as the schematic diagram covering embodiment of biochemistry detection unit;
Fig. 6 B is shown as the schematic diagram covering alternate embodiment of biochemistry detection unit;
Fig. 7 A is shown as the schematic diagram of biochip;
Fig. 7 B is shown as the schematic diagram of biochip Z axis embodiment one;
Fig. 7 C is shown as the schematic diagram of biochip Z axis embodiment two;
Fig. 7 D is shown as the schematic diagram of biochip Z axis embodiment three;
Fig. 7 E is shown as the schematic diagram of biochip X-Y axle embodiment one;
Fig. 7 F is shown as the schematic diagram of biochip X-Y axle embodiment two;
Fig. 8 is shown as the schematic diagram of biochemistry detection unit electrochrome embodiment;
Fig. 9 A is the schematic diagram of biochemical instrument separative element embodiment one;
Fig. 9 B is the schematic diagram of biochemical instrument separative element embodiment two;
Fig. 9 C is the schematic diagram of biochemical instrument separative element embodiment three.
Main element symbol description
1 biochemistry detection unit 60 releasing unit
15 reaction compartment 601 first accommodation spaces
17 closing lid 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 sprue 702 reactive end
261 opening 702 ' fluorescent reactive end, the first fluorescent reaction
27 runner ends
28 separative element 704 ferment
30 light-guide material plate 71 second affinity agents
35 reactants 711 second stick end
40 resistance sensing element 712 second fluorescent reactive end
41 resistance change signal 80 luminescence-producing reaction agent
The outer light source of 50 receptor 90
The fluorescent of 51 affinity end x first wave length scopes
The fluorescent of 511 shielded area y second wave length scopes
52 abutting ends
Embodiment
The corpse or other object for laboratory examination and chemical testing that biochemistry detection unit of the present invention 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.
In embodiment as 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 as shown in Figure 1A, is goodly arranged on light-guide material plate 30, and acceptor 50 is preferably immunoglobulin (Ig), but in other embodiments, acceptor 50 also can be other Amino acid fragments, adheres to the Amino acid fragment of a corpse or other object for laboratory examination and chemical testing 20 as having selectivity.In embodiment as shown in Figure 1A, acceptor 50 comprises affinity end 51 and abutting end 52, affinity end 51 can for exclusively adhering to a corpse or other object for laboratory examination and chemical testing 20, and this place speech " exclusively adhering to " refers to that affinity end 51 Amino acid fragment adheres to by hydrogen bond, affinity between Fan Dewali equimolecular and molecule.In embodiment shown in Figure 1A, abutting end 52 is preferably the Fc region of immunoglobulin (Ig), and abutting end 52 is preferably and is connected to light-guide material plate 30 in the mode of chemical bonded refractory; But in other embodiment (not shown), the annexation between abutting end 52 with light-guide material plate 30 is also connected with the affinity between molecule by hydrogen bond, Fan Dewali equimolecular.Therefore, containing distance between affinity end 51 and light-guide material plate 30, this distance is variant by the structure of factor receptor 50 and size, and distance is preferably between 0.1 μm to 0.1cm, to be more preferred between 1 μm to 1mm, between 10 μm to 100 μm.
As illustrated in the embodiment of figure ia, biochemistry detection unit 1 comprises resistance sensing element 40, resistance sensing element 40 and light-guide material plate 30 electric coupling, and the resistance value for sensing light-guide material 30 changes.Resistance sensing element 40 is preferably avometer or other instrument that can change for measured resistance value or device.
In embodiment as shown in Figure 1B, acceptor 50 can be designed to have with a corpse or other object for laboratory examination and chemical testing 20 affinity exclusively adhered to, now 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), and the affinity weakened between abutting end 52 and light-guide material plate 30, to abutting end 52 be easily separated with light-guide material plate 30 because affinity weakens, when acceptor 50 is together separated with light-guide material plate 30 with a corpse or other object for laboratory examination and chemical testing 20, light-guide material plate 30 is because of light-receiving area increase, thus the resistance value allowing resistance sensing element 40 sense light-guide material 30 changes.Resistance value change herein can, according to different light-guide materials 30, be designed to cause because illuminance increases the resistance value of different light-guide material to decline or rise, and then makes resistance sensing element 40 produce resistance change signal 41.In other words, resistance changes the change that signal 41 refers to 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 electromagnetic radiation can be converted into electric current, and electromagnetic radiation is often referred to ultraviolet light, visible ray and infrared light.In general after this kind of material static electrification, electrostatic just can be changed into electric current after penetrating by the illumination by special wavelength.In other words, these materials must be good insulating bodies darkling, become good conductor after light at once.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 being selected from selenium, selenium-tellurium alloy, cadmium sulfide, zinc paste, vulcanized lead, indium antimonide and above-mentioned substance.The light-guide material that light-guide material plate 30 of the present invention can be mixed by pure organic light-guide material, pure inorganic light-guide material or organic-inorganic formed.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.
In embodiment as shown in Figure 2 A, the biochemical instrument 2 of application biochemistry detection unit is better comprises releasing unit 60.In this embodiment, releasing unit 60 comprises the first accommodation space 601 and the second accommodation space 603, releasing unit 60 is not limited to only comprise two accommodation spaces, also an accommodation space or more than one accommodation space can only be comprised, time such as only containing an accommodation space, single accommodation space gets final product accommodating different material for reaction.In this embodiment, releasing unit 60 is preferably controllable reagent input media, this device can control its accommodation space comprised with the wafer that biochemical instrument 2 is built-in, the concrete mode controlled opens the time of accommodation space, the mode of release accommodation space content as controlled, and opens the order of each accommodation space respectively.In embodiment as shown in Figure 2 A, the 603 accommodating luminescence-producing reaction agent 80 of accommodating first affinity agent 70, second accommodation space of the first accommodation space 601.First affinity agent 70 comprises and sticks end 701 and reactive end 702.In the preferred embodiment, the first affinity agent 70 is another strain antibody, and this antibody exclusively adheres to the antibody of acceptor 50 compared with Canon.But in other embodiments, the first affinity agent 70 must not be antibody, also can be Amino acid sequence or the protein with acceptor 50 with selectivity affinity.In this embodiment, accommodation space is preferably the cavity that reagent input media includes; But in other embodiment (not shown), releasing unit 60 is the capsules for controlling release time, and the first accommodation space 601 and the second accommodation space 603 can be respectively the tiny capsules with identical or different dissolution time comprised in releasing unit 60 large capsule.In the embodiment of this capsule, releasing unit 60 also has same above-mentioned control mode, controls concrete mode and opens the time of accommodation space, the mode of release accommodation space content as controlled, and open the order of each accommodation space respectively.
As illustrated in the embodiment of figure 2 a, the sticking end 701 and exclusively can adhere to the affinity end 51 adhering to a corpse or other object for laboratory examination and chemical testing 20 of the first affinity agent 70.Therefore the first affinity agent 70 can be avoided and acceptor 50, because of non-specific combination, and the light-guide material resistance value making biochemistry detection unit 1 of the present invention sense photoconduction plate of material 30 changes, and then the puppet positive (False Positive) during observational measurement is avoided to react.In addition, the combination non-specific with acceptor 50 in order to avoid the first affinity agent 70 produces pseudo-positive reaction, as shown in the embodiment of fig. 2b, luminescence-producing reaction agent 80 is (as 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) or 3,3 ', 5,5 '-Tetramethyl benzidine) can react with the ferment 704 (as peroxidase peroxidase) of reactive end 702 end of the first affinity agent 70 after send the fluorescent of particular range of wavelengths, this reaction is also called enzyme immunoassay (ELISA).In this embodiment, the wavelength coverage that fluorescent sends is preferably and is selected from 620 ~ 750nm, 495 ~ 570nm and 358 ~ 461nm; But in other embodiments, the best is selected from 575 ~ 900nm, 470 ~ 610nm, 300 ~ 480nm.After above-mentioned fluorescent exposes to light-guide material plate 30, coordinate suitable light-guide material and resistance sensing element 40, namely 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, after a corpse or other object for laboratory examination and chemical testing 20 adhesion receptor 50, react by luminescence-producing reaction agent 80 and ferment 704 fluorescent sent, photoconduction plate of material 30 can be excited and change the resistance value of light-guide material.Because a corpse or other object for laboratory examination and chemical testing 20 is generally entrained by fluid, the scope of fluid is including but not limited to air, liquid and semisolid (colloid).Because fluid is except being carried into acceptor 50 by a corpse or other object for laboratory examination and chemical testing 20, also can carry outside without the first affinity agent 70 adhered to.
In embodiment as shown in Figure 3, the biochemical instrument 2 of application biochemistry detection unit comprises releasing unit 60 further, and the releasing unit 60 of this embodiment comprises the first accommodation space 601, is single accommodation space in this embodiment.Accommodating first affinity agent 70 of first accommodation space 601, releasing unit 60 can control the first accommodation space 601 and discharge at least one first affinity agent 70, the first affinity agent 70 to comprise and stick end 701 and reactive end 702.In this embodiment, adhere to end 701 and adhere to the affinity end 51 adhering to a corpse or other object for laboratory examination and chemical testing 20.Different from previous embodiment be in, the reactive end 702 that the first affinity agent 70 comprises are light waves from sending particular range of wavelengths.Specifically, this principle is radiommunoassay (radioimmunoassay).In this embodiment, reactive end 702 be preferably with merge isotope (as
12c,
14c,
131i) Amino acid is unit; But in other embodiments, adhere to end 701 also can be designed to adhere to specific isotope (as
12c,
14c,
131i) Amino acid sequence, therefore reactive end 702 is now isotope species.In this embodiment, if when reactive end 702 is isotope, its light wave certainly sent is including but not limited to α, β or gamma-rays.In other embodiments, reactive end 702 also can be self luminous fluoroprotein, and in this embodiment, the particular range of wavelengths that reactive end 702 sends is preferably and is selected from 620 ~ 750nm, 495 ~ 570nm and 358 ~ 461nm; But in other embodiments, the best is selected from 575 ~ 900nm, 470 ~ 610nm, 300 ~ 480nm.In embodiment as shown in Figure 3, when the x radiation x that reactive end 702 sends certainly is to light-guide material plate 30, resistance sensing element 40 can respond to light-guide material by ray excite and the resistance value that changes, and then produce resistance and change signal 41.
In embodiment as shown in Figure 4, the biochemical instrument 2 of application biochemistry detection unit comprises releasing unit 60 and outer light source 90 further, and releasing unit 60 disengages at least one first affinity agent 70, first affinity agent 70 and comprises and stick end 701 and fluorescent reactive end 702 '.Stick end 701 and adhere to the affinity end 51 adhering to a corpse or other object for laboratory examination and chemical testing 20.Different from previous embodiment be in, after fluorescent reactive end 702 ' is subject to the illumination of outer light source 90, fluorescent reactive end 702 ' can send the fluorescent of particular range of wavelengths, and 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 the fluoroprotein (as Green Fluorescent Protein GFP, red fluorescent protein HcRed, yellow fluorescent protein ZsYellow etc.) sending different wavelength range, fluorescent reactive end 702 ' send light wave particular range of wavelengths be preferably and be selected from 620 ~ 750nm, 495 ~ 570nm and 358 ~ 461nm; But in other embodiments, the best is selected from 575 ~ 900nm, 470 ~ 610nm, 300 ~ 480nm.By the light-guide material that collocation design is applicable to, light-guide material plate 30 can change resistance value by fluorescent excites, and therefore resistance sensing element 40 can be responded to and produce resistance change signal 41.
In qualitative analysis, pseudo-positive reaction often can cause the erroneous judgement of testing result, in order to reduce the generation of pseudo-positive reaction.As shown in the embodiment of figure 5 a, the releasing unit 60 applying the biochemical instrument 2 of biochemistry detection unit comprises the first accommodation space 601 and the second accommodation space 603.Accommodating first affinity agent 70, first affinity agent 70 of first accommodation space 601 comprises first and sticks end 701 and the first fluorescent reactive end 702 '.Accommodating second affinity agent 71, second affinity agent 71 of second accommodation space 603 comprises second and sticks end 711 and the second fluorescent reactive end 712.First sticks end 701 adheres to the affinity end 51, the second having adhered to a corpse or other object for laboratory examination and chemical testing 20 in specific manner and sticks end 711 and adhere to shielded area 511 in specific manner, and shielded area 511 is defined as acceptor 50 part covered when a corpse or other object for laboratory examination and chemical testing 20 adheres to affinity end 51.In this embodiment, the biochemical instrument 2 of application biochemistry detection unit separately comprises outer light source 90, and the wavelength coverage of the light that outer light source 90 sends as previously mentioned.After the second affinity agent 71 sticks shielded area 511, be subject to light that outer light source 90 sends when exposing to the second fluorescent reactive end 712, second fluorescent reactive end 712 will exhale the fluorescent x of first wave length scope, due in adjacent biochemistry detection unit 1, first of first affinity agent 70 sticks after end 701 adheres to the affinity end 51 adhering to a corpse or other object for laboratory examination and chemical testing 20, because the first adhesion end 701 is connected to fluorescent reactive end 702 ', after the fluorescent x that this fluorescent reactive end 702 ' is subject to first wave length scope excites, the fluorescent y of second wave length scope will be sent, and then excite photoconduction material and change the resistance value of light-guide material plate 30, thus produce resistance and change signal 41.Change signal 41 because adjacent two biochemistry detection unit 1 only have one of them can produce resistance, therefore can get rid of adjacent two biochemistry detection unit 1 by this all has the pseudo-positive reaction producing resistance change signal 41.Because the affinity end 51 of acceptor 50 and the distance of light-guide material plate 30 can affect the illumination that second wave length scope fluorescent y irradiates the light-guide material plate 30 be connected in the second affinity agent 71.Therefore, under faint illumination, the biochemistry detection unit 1 that the second affinity agent 71 engages can't produce resistance and change signal 41; In addition, in other embodiment (not shown), also can the polaroid that can filter second wave length scope fluorescent y be set between adjacent biochemistry detection unit 1, in the biochemistry detection unit 1 that the fluorescent y of second wave length scope can only be engaged in the first affinity agent 70, produces reaction.In this design, adjacent two biochemistry detection unit 1 can be got rid of and all have the pseudo-positive reaction producing resistance change signal 41.In this embodiment, the fluorescent of first wave length scope and second wave length scope is preferably and is selected from 620 ~ 750nm, 495 ~ 570nm and 358 ~ 461nm; But in other embodiments, the best is selected from 575 ~ 900nm, 470 ~ 610nm, 300 ~ 480nm, but first wave length scope is not overlapped in second wave length scope.For example, if when the first wave length scope of fluorescent x is 620 ~ 750nm, the second wave length scope of fluorescent y then can be designed to 495 ~ 570nm or 358 ~ 461nm.
In alternate embodiment as shown in Figure 5 B, the releasing unit 60 of the biochemical instrument 2 of application biochemistry detection unit comprises the first accommodation space 601, second accommodation space 603 and the 3rd accommodation space 605.First accommodation space 601 comprises accommodating second affinity agent 71 of the first affinity agent 70, second accommodation space 603, and the 3rd accommodation space 605 comprises at least one luminescence-producing reaction agent 80.When the first affinity agent 70 and the second affinity agent 71, after adhering to biochemistry detection unit 1 in previous embodiment, releasing unit 60 discharge at least one luminescence-producing reaction agent 80 and will to spread gradually and after acting on the second fluorescent reactive end 712, send the fluorescent x of first wave length scope, and first wave length scope fluorescent x can excite the first fluorescent reactive end 702 ' further and send the fluorescent y of second wave length scope.In this embodiment, adjacent two biochemistry detection unit 1 can be got rid of and all have the pseudo-positive reaction producing resistance change signal 41, but this embodiment is the source providing fluorescent mutually to excite with luminescence-producing reaction agent 80, and not beyond the mode of light source 90 source that provides fluorescent mutually to excite.In alternate embodiment as shown in Figure 5 B, the fluorescent of first wave length scope and second wave length scope is preferably and is selected from 620 ~ 750nm, 495 ~ 570nm and 358 ~ 461nm; But in other embodiments, the best is selected from 575 ~ 900nm, 470 ~ 610nm, 300 ~ 480nm, but first wave length scope is not overlapped in second wave length scope.
In embodiment as shown in Figure 6A, a kind of biochemistry detection unit 1 being 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 irradiates in acceptor 50, light-guide material plate 30, in this embodiment, the affinity end 51 of acceptor 50 can adhere to a larger 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 large or have larger area coverage, so that light subject 20 covers and produces capture-effect, light-guide material plate 30 is made to change signal 41 because not receiving the irradiation of light without generation resistance.Shown in the embodiment of Fig. 6 B, a corpse or other object for laboratory examination and chemical testing 20 epi-position (epitope) that the affinity end 51 of the acceptor 50 of adjacent biochemistry detection unit 1 can adhere to is different, but because a large-scale corpse or other object for laboratory examination and chemical testing 20 has different epi-positions 21, if when therefore design can adhere to the adjacent biochemistry detection unit 1 of the different epi-position of a large-scale corpse or other object for laboratory examination and chemical testing 20 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 the non-specific capture-effect that minimizing Fig. 6 A embodiment produces because of other a non-corpse or other object for laboratory examination and chemical testing 20 materials of non-specific adhesion, and then reduce pseudo-negative (False Negative) reaction.
Namely biochemistry detection unit 1 of the present invention comprises light-guide material plate 30, acceptor 50 and resistance sensing element 40 as above-mentioned.By assembling many biochemistry detection unit 1, can be formed and detect wafer or be referred to as biochip.Better in biochip have 106 to 1012 biochemistry detection unit 1, but in the design wafer that other are different, the quantity of biochemistry detection unit 1 is not as limit.In the preferred embodiment of biochip, the design of biochemistry detection unit 1 non-equal.For example, embodiment as shown in Figure 6B, adjacent biochemistry detection unit 1 is just not identical.Due to biochip, as shown in the embodiment of Fig. 7 A, comprise a plurality of biochemistry detection unit 1.In addition, as shown in Figure 7 B, if with Z axis, each biochemistry detection unit 1 from top to bottom can arrange in order, often then having reaction compartment 15 between row biochemistry detection unit 1 can for the fluid carrying a corpse or other object for laboratory examination and chemical testing 20, fluid comprises air, liquid and semisolid (colloid), and when a corpse or other object for laboratory examination and chemical testing 20 is transported to biochemistry detection unit 1 place by fluid, acceptor 50 will stick according to selectivity affinity and a corpse or other object for laboratory examination and chemical testing 20.In embodiment as shown in Fig. 7 C and Fig. 7 D, the arrangement mode of biochemistry detection unit 1 also can have other modes, alternating expression arrangement as seen in figure 7 c.Alternating expression arrangement can increase the unit reaction compartment 15 of biochemistry detection unit 1, biochemistry detection unit 1 also can be avoided too close simultaneously as far as possible, to such an extent as to produce pseudo-positive reaction.Closed type arrangement as illustrated in fig. 7d can reduce the volume of biochip, be easy to be convenient for carrying, because each biochemistry detection unit 1 is too close, therefore the setting of closing lid 17 is needed, the better top being arranged at often row biochemistry detection unit 1 of closing lid 17, the pseudo-positive reaction produced to prevent fluorescent scattering.In addition, closed type arrangement unit reaction compartment 15 will be caused to reduce, therefore for the fluid containing an a large amount of corpse or other object for laboratory examination and chemical testing 20 or sensitiveer biochemistry detection unit 1 just more applicable.This is that unit reaction compartment 15 reduces due under the constant prerequisite of a corpse or other object for laboratory examination and chemical testing 20 quantity in per unit fluid, 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 the quantity increasing a corpse or other object for laboratory examination and chemical testing 20 in per unit fluid.
In addition, as shown in the embodiment of Fig. 7 E and Fig. 7 F, the arrangement of biochemistry detection unit 1, with X-Y axle, light-guide material plate 30 is uninevitable as shown in Figure 7 F, by identical material light-guide material plate 30 form and arrange, as 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.Different mutual arrangement mode as seen in figure 7e can avoid the pseudo-positive reaction produced during fluorescent scattering further.This is because the fluorescent frequency of scattering can not excite different light-guide material plates 30, and scattering fluorescent is different for the illumination of every sheet light-guide material plate 30, even if light-guide material plate 30 too far away can excite by this fluorescent frequency, but because illumination is not enough, resistance sensing element 40 also cannot be made to produce induction.
As shown in Figure 8, the biochemistry detection unit 1 being 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 arranged on light-guide material plate 30, when a corpse or other object for laboratory examination and chemical testing 20 contact reaction agent 35, reactant 35 can produce chemical change and variable color, because the reactant 35 after variable color can affect the light illumination that outer light source 90 projects, therefore will weaken the illumination of outer light source irradiation in light-guide material plate 30.Because illumination changes, resistance sensing element 40 mat and light-guide material plate 30 electric coupling and produce resistance and change signal 41.In an embodiment, because reactant 35 is directly arranged on light-guide material plate 30, therefore reactant 35 also can be considered a kind of acceptor 50, although 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 react with specific compound, or is designed to and particular functional radical reaction, and therefore reactant 35 can detect single compound, also can detect specific derivatives.
In embodiment as shown in Figure 9 A, the biochemical instrument 2 of application biochemistry detection unit comprises sprue 26, at least one runner 27 and separative element 28 further.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; But in other embodiment (not shown), light-guide material plate 30 is arranged in runner 27 or sprue 26.Be arranged at opening 261 because biochemical instrument 2 has separative element 28, selectively allow 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 when may cause supersaturation, separative element 28 selectively makes a corpse or other object for laboratory examination and chemical testing 20 cannot enter runner 26, therefore a corpse or other object for laboratory examination and chemical testing 20 and biochemistry detection unit 1 react and can't produce supersaturation, and make the biochemical instrument 2 of application biochemistry detection unit can reach the quantitative effect of analysis.In embodiment as shown in Figure 9 A, separative element 28 is valve, valve 28 electric signal contact resistance sensing element 40, when the biochemistry detection unit 1 of runner 27 end is tending towards saturated with the adhesive reaction of a corpse or other object for laboratory examination and chemical testing 20 or metachromasia, when the change of sensing resistor value is exceeded predetermined value by resistance sensing element 40, resistance sensing element 40, by after output control signal to valve 28, makes 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, the effect that thus analysis of attainable cost invention is quantitative.
In embodiment as shown in Figure 9 B, the biochemical instrument 2 of application biochemistry detection unit comprises sprue 26 and a plurality of runner 27 as N
1, N
2n
n.Each runner 27 is opening 261 with the junction of sprue 26, in this embodiment, be positioned at that opening 261 place is better arranges separative element 28, separative element 28 can be electrode group, electrode group 28 will produce dielectrophoretic force (dielectrophoretic force), the dielectrophoretic force produced by electrode group 28 can use to 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 arrives runner 27 end and react with biochemistry detection unit 1.But in other embodiments, separative element 28 also can be optics folder (optical tweezer), optics folder 28 is separated a 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 to react with the supersaturation of biochemistry detection unit 1.
In embodiment as shown in Figure 9 C, the connection between the sprue 26 of the biochemical instrument 2 of application biochemistry detection unit and runner 27 is opening 261.In this embodiment, separative element 28 is for being arranged at the semi-permeable diaphragm at opening 261 place, a corpse or other object for laboratory examination and chemical testing 20 for semi-permeable diaphragm 28 optionally penetrating different size, and can 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 runner 27 will reach 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 supersaturation to react.And the effect that the analysis of attainable cost invention is quantitative.
The present invention is described by above-mentioned related embodiment, but above-described embodiment is only enforcement example of the present invention.Must it is noted that the embodiment disclosed limit the scope of the invention.On the contrary, be contained in the spirit of claim and the amendment of scope and equalization to arrange and be all included within the scope of the present invention.
Claims (4)
1. be used for the biochemistry detection unit of detection one corpse or other object for laboratory examination and chemical testing, comprise:
One outer light source;
One light-guide material plate, this outer light source irradiation is in this light-guide material plate;
One reactant, to be arranged on this light-guide material plate and exclusively to adhere to this corpse or other object for laboratory examination and chemical testing, when 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 irradiation 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 produced because this light-guide material plate illumination changes for sensing changes.
2. a biochemical instrument for the biochemistry detection unit of application as described in claims 1, comprises further:
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. the biochemical instrument as described in claims 2, wherein this separative element comprises a semi-permeable diaphragm.
4. the biochemical instrument as described in claims 2, wherein this separative element comprises a valve, this valve electric signal connects this resistance sensing element, when the change of this this resistance value of resistance sensing element sensing exceedes predetermined value, after this resistance sensing element exports a control signal to this valve, this opening of this valve closing.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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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| CN103293191B true 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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| 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 |
| JP3547599B2 (en) * | 1997-12-10 | 2004-07-28 | 独立行政法人 科学技術振興機構 | Gene sensor |
| 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 |
| CN1256584C (en) * | 2003-01-08 | 2006-05-17 | 力捷电脑股份有限公司 | Biological chip capable of raising measurement reliability and its method |
| KR100667339B1 (en) * | 2005-01-11 | 2007-01-12 | 삼성전자주식회사 | Biosensor and biosensor system |
| DE102005018337A1 (en) * | 2005-04-20 | 2006-11-02 | Micronas Gmbh | Micro-optical detection system and method for determining temperature-dependent parameters of analytes |
| CN100551550C (en) * | 2006-09-25 | 2009-10-21 | 瑞鼎科技股份有限公司 | Fluid fine particle separating device |
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| CN102192902A (en) | 2011-09-21 |
| CN102192902B (en) | 2013-12-11 |
| CN103293191A (en) | 2013-09-11 |
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