CN1453366A - Micro sprue system of biochip array - Google Patents

Micro sprue system of biochip array Download PDF

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Publication number
CN1453366A
CN1453366A CN 02118400 CN02118400A CN1453366A CN 1453366 A CN1453366 A CN 1453366A CN 02118400 CN02118400 CN 02118400 CN 02118400 A CN02118400 A CN 02118400A CN 1453366 A CN1453366 A CN 1453366A
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China
Prior art keywords
substrate
reaction zone
runner
sprue system
array
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CN 02118400
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CN1193105C (en
Inventor
苏友欣
鲁希连
龙训民
董忠和
刘大章
许世明
林世明
王安邦
李世光
林启万
黄荣山
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GONGZHUN PRECISION INDUSTRY Co Ltd
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GONGZHUN PRECISION INDUSTRY Co Ltd
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Abstract

The micro sprue system of biochip array includes mainly one substrate, and several notched reaction zones in preset depth on the substrate for fixing the biological probes. Each reaction zone has one drawing sprue set in the height above the probe on the side wall and there are drawing port communicating the drawing sprues on one side of the substrate. So, sample solution to be tested is introduced from the reaction area, and unreacted sample solution is drawn out form the drawing port and via the drawing sprue to constitute the micro sprue system of biochip array.

Description

The micro sprue system of array biochip
Technical field
The present invention is the micro sprue system of relevant a kind of array biochip, refers to the micro sprue system on a kind of DNA of applying to, protein or the biomass cells micro-array chip especially.
Background technology
Pioneering theoretical Li Cha-Feynman (Richard P.Feynman) doctor who obtains Nobel prize special honours with quantum electrodynamics, in nineteen fifty-nine American Physical Society's annual meeting, by theming as the speech of " peep and study carefully on earth; space unlimited (There is a plenty of room at thebottom.) ", lead people to enter a brand-new field in the scientific circles, begin with the Encyclopaedia Britannica on the syringe needle in the annual meeting, and disclosed the ultra micro electron microscope successively, small counter, small factory, the theory in the small worlds of downsizing such as atom reorganization, thereby become " MEMS (micro electro mechanical system) (micro electromechanical system; Or " microsystems technology (micro-system technology MEMS) "; MST) " the fonder of a religious sect.
Along with human genome is understood the ordering first draft that plan (Human Genome Project) discloses DNA (DNA) in the gene karyomit(e), lead human history to enter the biomedical nineteen sixty that matches in excellence or beauty of 21 century for the new milestone that lands on the moon, scientist's next problem is to understand meaning and its mutual relationship of tens thousand of gene representatives, and aleuroplast (proteomics) function and structural research, and solve the best sharp weapon of this small, complicated biomolecules just by formed biochips of industrial technology such as micro electronmechanical, micro-systems.
Biochip mainly is to utilize industrial technologies such as microelectronics, micromechanics, to have specific biomolecules is fixed on the base material of thumbnail size as bioprobe (biologicalprobe), the target substance (target) that does not have corresponding bioprobe with the sample solution of judging the desire detection, and produce label information as judgment mechanism by chemical reaction, analyse and compare for the subsequent optical sensing apparatus.
If the idea with chip-shaped little laboratory (laboratory-on-a-chip) is treated biochip, to be distinguished by the operating process of bioprobe and sample solution, it mainly can be divided into following two kinds of systems:
One, open system: promptly be generally only to have a biochip of reaction zone, only contain the reaction zone that is fixed with bioprobe on it, it can be provided with a plurality of reaction zones (promptly being to assemble the array point that forms with bioprobe) on chip, the adding of its sample solution is with detach need be by external equipment, as dripping pin, suction needle or cleaning disc, though such design is comparatively convenient when the filling sample solution, but when extracting, each array point all will dispose a suction needle or off-line and put in cleaning disc and clean, make member too complicated, simultaneously, suction needle with vertical mode detaches the fixing of easy destruction bioprobe and effect back bonded target substance, therefore still remains to be improved.
Two, closed system: but have the reaction zone of fixing biological probe on it and cooperate sample solution to inject, the fluid channel that detaches, and be provided with higher microfluidic valve of complexity and cost of manufacture and introduction valve device in the runner stage casing, though this system can effectively isolate sample solution and extraneous contacting, reach good experiment control, but, for fear of the consideration on technology and the cost, a chip can only be provided with a minority reaction zone, be difficult to be applied on the array chip in differential responses district, and in the injection side of fluid channel, be easy to generate the obstruction of bubble and microbiological specimens, cause the puzzlement on the actual detected, therefore still remain to be improved.
Summary of the invention
Main purpose of the present invention is to solve the above problems, and avoids the existence of defective, the invention provides a kind of a plurality of reflecting points and only need a micro sprue system that detaches the array biochip of device of avoiding blocking, arranging in pairs or groups.
For achieving the above object, the present invention is the micro sprue system of array biochip, mainly has a substrate, be to be concaved with at least more than one for bioprobe fixed reaction zone on substrate with a predetermined depth, and be provided with one in the position that each reaction zone sidewall surpasses the bioprobe height and extract runner, and has the mouth that detaches that is communicated with the extraction runner in substrate one side, like this, add the sample solution that desire detects by reaction zone, and to extract runner unreacted sample solution is extracted out by detaching mouth, just constituted the micro sprue system of an array formula biochip.
Relevant detailed description of the present invention and technology contents now just cooperate graphic being described as follows:
Description of drawings
Fig. 1 is a floor map of the present invention;
Fig. 2 is the local enlarged diagram of the present invention the 1st figure;
Fig. 3 is a diagrammatic cross-section of the present invention;
Fig. 4 is the another embodiment of the present invention diagrammatic cross-section;
Fig. 5 is an embodiment diagrammatic cross-section more of the present invention.
Embodiment
See also Fig. 1,2,3, it is plane of the present invention, amplify and diagrammatic cross-section the part of the 1st figure, as shown in the figure: the present invention is a kind of micro sprue system of array biochip, mainly has a substrate 10, be to be concaved with at least more than one for bioprobe 70 fixed reaction zones 20 on substrate 10 with a predetermined depth, and be provided with one in the position that each reaction zone 20 sidewall surpasses bioprobe 70 height and extract runner 30, and substrate 10 1 sides have be communicated with to extract runner 30 detach mouthfuls 40, like this, add the sample solution that desire detects by reaction zone 20, and to extract runner 30 unreacted sample solution is extracted out by detaching mouth 40, just constituted the micro sprue system of an array formula biochip.
During manufacturing, substrate 10 can be made by glass or silicon substrate, as shown in the figure, being concaved with 16 reaction zones 20 by micro-electromechanical technology first array on substrate 10 (but does not exceed with 16 reaction zones 20, also can be 2 * 2,3 * 3 or 5 * 5 matrixes), and correspond to each reaction zone 20 sidewall and be provided with a secondary fluid course 32, and be connected longitudinally on the sprue 31 with a confluence 33 with each secondary fluid course 32 in the delegation, extraction runner 30 is equated in each reaction zone 20 to the distance that detaches mouth 40 of the same transverse layers of array, like this, can be controlled at the same vertically extraction time of each reaction zone 20, make things convenient for user's detection of packets, in addition, these secondary fluid course 32 bearing of trends are by reaction zone 20 centers, in order to when detaching, in reaction zone 20, to form symmetrical eddy current, avoid destroying bioprobe 70.
Moreover sprue 31 and secondary fluid course 32 mainly are to be laid on the substrate 10 with straight line, and each confluence 33 2 runner angle is greater than 135 °, in order to form level and smooth corner, make extraction smooth more.
During use, earlier at each reaction zone 20 bottom fixing biological probe 70, the sample solution that desire is detected adds reaction zone 20, at this moment, owing to extract runner 30 apertures less than 200 μ m, sample solution can't leak via extracting runner 30, and carries sample solution by the predetermined depth of reaction zone 20, and bioprobe 70 and sample solution can fully be reacted; After the reaction; the flow rate control device (not shown) that detaches mouth 40 with connection detaches; because the extraction runner 30 of same transverse layers is all equated by reaction zone 20 to the distance that detaches mouth 40 in array; therefore; flow rate control device will be drained sample solution successively by first transverse layers to the, four transverse layers; simultaneously; be higher than bioprobe 70 owing to extract runner 30; its extraction dynamics can not be applied directly on the bioprobe 70; can effectively protect bioprobe 70 and bonded target compound; after treating that each layer reaction zone 20 interior sample solutions all detach, can utilize the optics judgment means to scan comparison.
For easily manufactured, see also Fig. 4, it is the another embodiment of the present invention diagrammatic cross-section, as shown in the figure: the present invention is a kind of micro sprue system of array biochip, it comprises a hypocoxa 50 and a upper substrate 60, on hypocoxa 50 surfaces is to be concaved with a plurality of bioprobe 70 fixed reaction zone 20a that supply, and be provided with a perforation 61 in upper substrate 60 corresponding each reaction zone 20a position, and be laid with extraction runner 30a in upper substrate 60 bottom surfaces, in addition upper substrate 60 1 sides have be communicated with extract runner 30a detach mouthfuls 40, like this, the sample solution that adds the desire detection is on reaction zone 20a, and to extract runner 30a unreacted sample solution is extracted out by detaching mouth 40, just constituted the micro sprue system of an array formula biochip.
In addition, see also Fig. 5, it is an embodiment diagrammatic cross-section more of the present invention, as shown in the figure: the present invention is a kind of micro sprue system of array biochip, it comprises a hypocoxa 50a, a middle substrate 80 and a upper substrate 60a, be provided with a plurality of for bioprobe 70 fixed reaction zone 20b on hypocoxa 50a surface, and be provided with a through hole 81 at middle substrate 80 corresponding each reaction zone, and be provided with the extraction runner 30b of perforation 61a and communication bores 61a in the corresponding through hole 81 of upper substrate 60a and bottom surface thereof, have in upper substrate 60a one side in addition and be communicated with mouthful 40a that detaches that extracts runner 30b, like this, the sample solution that adds the desire detection is on reaction zone 20b, and to extract runner 30b unreacted sample solution is extracted out by detaching mouthful 40a, just constituted the micro sprue system of an array formula biochip.
Above-mentioned upper substrate, middle substrate and hypocoxa can be macromolecular material (for example polymethylmethacrylate polymethyl methacrylate), plastics, glass or silicon substrates with low cost, and mutually combine with heat welded, anodic bonding or interface sticking agent mode, like this, can separately make or traditional micro-processing technology making reaction zone and extraction runner, meet market demand in order to reduce cost with micro electronmechanical.

Claims (10)

1. the micro sprue system of an array biochip, it is characterized in that: described micro sprue system mainly has a substrate (10), be to be concaved with at least more than one for bioprobe (70) fixed reaction zone (20) on substrate (10) with a predetermined depth, and be provided with one in the position that each reaction zone (20) sidewall surpasses bioprobe (70) height and extract runner (30), and have detach mouthful (40) that are communicated with extraction runner (30) in substrate (10) one sides, like this, add the sample solution that desire detects by reaction zone (20), and to extract runner (30) unreacted sample solution is extracted out by detaching mouthful (40), just constituted the micro sprue system of an array formula biochip.
2. the micro sprue system of array biochip according to claim 1, it is characterized in that, described extraction runner (30) equates by detaching mouthful (40) reaction zone (20) distance to same transverse layers, in order to be controlled at same vertically the extraction time and the dynamics of each reaction zone (20).
3. the micro sprue system of array biochip according to claim 1, it is characterized in that, corresponding each reaction zone of described extraction runner (30) (20) has a secondary fluid course (32), and the bearing of trend of described secondary fluid course (32) is by reaction zone (20) center, in order to when detaching, in reaction zone (20), to form symmetrical eddy current, avoid destroying bioprobe (70), and each secondary fluid course (32) is to be communicated in a sprue (31) with a confluence (33).
4. the micro sprue system of array biochip according to claim 1, it is characterized in that, described extraction runner (30) mainly is to be laid on the substrate (10) with straight line, and at each straight line plotted point is with greater than 135 ° the adjacent connection of angle, makes extraction smooth more in order to form level and smooth corner.
5. the micro sprue system of array biochip according to claim 1 is characterized in that, described substrate (10) can be manufactured by glass or silicon substrate and form.
6. the micro sprue system of array biochip according to claim 1, it is characterized in that, described substrate (10) be can a hypocoxa (50) and a upper substrate (60) constitute, on hypocoxa (50) surface is to be concaved with a plurality of bioprobe (70) fixed reaction zones (20a) that supply, and corresponding each reaction zone of upper substrate (60) (20a) be provided with one the perforation (61), and be laid with the extraction runner (30a) of communication bores (61) at upper substrate (60) face, have in upper substrate (60) one sides in addition and be communicated with detach mouthful (40) of extracting runner (30a), like this, add the sample solution that desire detects by reaction zone (20a), and to extract runner (30a) unreacted sample solution is extracted out by detaching mouthful (40), just constituted the micro sprue system of an array formula biochip.
7. the micro sprue system of array biochip according to claim 6, it is characterized in that, described upper substrate (60) and hypocoxa (50) are macromolecular materials, polymethylmethacrylate for example, plastics, glass or silicon substrate, and mutually combine with heat welded, anodic bonding or interface sticking agent mode.
8. the micro sprue system of array biochip according to claim 1, it is characterized in that, described substrate (10) can be by a hypocoxa (50a), a middle substrate (80) and a upper substrate (60a) constitute, be provided with a plurality of for bioprobe (70) fixed reaction zone (20b) on hypocoxa (50a) surface, and be provided with a through hole (81) at corresponding each reaction zone of middle substrate (80) (20b), and be provided with the extraction runner (30b) of perforation (61a) and communication bores (61a) in the corresponding through hole of upper substrate (60a) (81) and bottom surface thereof, have in upper substrate (60a) side in addition and be communicated with detach mouthful (40a) who extracts runner (30b), like this, add the sample solution that desire detects by reaction zone (20b), and to extract runner (30b) unreacted sample solution is extracted out by detaching mouthful (40a), just constituted the micro sprue system of an array formula biochip.
9. the micro sprue system of array biochip according to claim 8 is characterized in that, described perforation (61) is greater than through hole (81).
10. the micro sprue system of array biochip according to claim 8, it is characterized in that, described upper substrate (60a), middle substrate (80) and hypocoxa (50a) are the macromolecular materials that is respectively with low cost, polymethylmethacrylate for example, plastics, glass or silicon substrate, and mutually combine with heat welded, anodic bonding or interface sticking agent mode.
CNB021184003A 2002-04-25 2002-04-25 Micro sprue system of biochip array Expired - Fee Related CN1193105C (en)

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CN1193105C CN1193105C (en) 2005-03-16

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103417212A (en) * 2012-05-21 2013-12-04 中华大学 Biological probe assembly
CN104797699A (en) * 2011-09-14 2015-07-22 昆士兰大学 Substance exposure apparatus
CN105408022A (en) * 2013-05-14 2016-03-16 哈佛学院院长等 Apparatus and method for the rapid production of droplets

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104797699A (en) * 2011-09-14 2015-07-22 昆士兰大学 Substance exposure apparatus
CN104797699B (en) * 2011-09-14 2019-04-19 昆士兰大学 Substance exposing device
CN103417212A (en) * 2012-05-21 2013-12-04 中华大学 Biological probe assembly
CN103417212B (en) * 2012-05-21 2015-09-16 中华大学 Bioprobe assembly
CN105408022A (en) * 2013-05-14 2016-03-16 哈佛学院院长等 Apparatus and method for the rapid production of droplets
CN105408022B (en) * 2013-05-14 2018-03-30 哈佛学院院长等 For quickly producing the apparatus and method of droplet
US10151429B2 (en) 2013-05-14 2018-12-11 President And Fellows Of Harvard College Rapid production of droplets
US10876688B2 (en) 2013-05-14 2020-12-29 President And Fellows Of Harvard College Rapid production of droplets

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