[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN1467499A - Surface tension-driven liquid flow on a chip high-density microarray liquid transfer device - Google Patents

Surface tension-driven liquid flow on a chip high-density microarray liquid transfer device Download PDF

Info

Publication number
CN1467499A
CN1467499A CNA021267294A CN02126729A CN1467499A CN 1467499 A CN1467499 A CN 1467499A CN A021267294 A CNA021267294 A CN A021267294A CN 02126729 A CN02126729 A CN 02126729A CN 1467499 A CN1467499 A CN 1467499A
Authority
CN
China
Prior art keywords
liquid
liquid transfer
chip
surface tension
transfer device
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CNA021267294A
Other languages
Chinese (zh)
Other versions
CN1195984C (en
Inventor
田昭武
林华水
周勇亮
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Xiamen University
Original Assignee
Xiamen University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Xiamen University filed Critical Xiamen University
Priority to CN 02126729 priority Critical patent/CN1195984C/en
Publication of CN1467499A publication Critical patent/CN1467499A/en
Application granted granted Critical
Publication of CN1195984C publication Critical patent/CN1195984C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Landscapes

  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

涉及一种芯片化的高密度微阵列液体转移装置,设有一片状载体,片状载体上设有微阵列超微量的液体转移组合,所说的组合包括储液部、液体转移头和微通道,所说的微通道联通于储液部与液体转移头之间。采用高密度、芯片化微阵列液体转移芯片结构,而且整个装置的微量液体转移的微液流过程可以只靠表面张力的作用,因此相邻的液体转移组合之间的距离可以很近,每个装置所排列的液体转移组合可以有成千上万组;制造成本低,避免交叉污染。由于样品为预设定体积的不同样品溶液,转移体积的重现性较好。样品预设定体积可设定为亚纳升或皮升体积,其结果是每一生物芯上可容纳更多更密集的阵列点,达到高速度、高精确度、高密度以及芯片化、低成本的目的。

It relates to a chip-based high-density microarray liquid transfer device, which is provided with a sheet-like carrier, and the sheet-like carrier is provided with a microarray ultra-micro liquid transfer combination, and the said combination includes a liquid storage part, a liquid transfer head and a microchannel , said microchannel communicates between the liquid storage part and the liquid transfer head. High-density, chip-based microarray liquid transfer chip structure is adopted, and the micro-fluid flow process of the micro-liquid transfer of the entire device can only rely on the effect of surface tension, so the distance between adjacent liquid transfer combinations can be very close, each There can be tens of thousands of liquid transfer combinations arranged in the device; the manufacturing cost is low, and cross-contamination is avoided. Since the samples are different sample solutions with preset volumes, the reproducibility of the transferred volume is good. The pre-set volume of the sample can be set to sub-nanoliter or picoliter volume. As a result, more and denser array points can be accommodated on each bio-core, achieving high speed, high precision, high density, and chip-based, low-cost cost purposes.

Description

The high-density micro-array liquid transferring equipment of the chipization of surface tension driving liquid stream
The high-density micro-array liquid that the present invention relates to a kind of chipization shifts (microarrayer technique on chip) device, this device is that thousands of groups liquid is integrated on the chip with shifting combination arrayization, be referred to as micro-array liquid and shift chip (microarrayer chip), this is a kind of ultramicron liquid transfer device of high-efficiency and low-cost of high density arraysization of accurate CONTROL VOLUME.
Biology/chemical microarray (Biological/chemical microarray) is meant industrial technologies such as utilizing microelectronics, micromechanics, on solid phase carriers such as glass, silicon chip, plastics, press certain position array fixed biologically or chemical molecular, make and be applied to biology/chemico-analytic product, its effective object can be gene, protein or cell tissue etc.Biology/chemical microarray at present development product comprise genetic chip (Genechip, DNAchip or Microarray), protein-chip (protein chip), micro-fluid chip (Microfluidics) and lab-on-a-chip (Labs-on-a-chip) etc.Genetic chip wherein or title dna microarray are at present technical relatively ripe, the maximum a kind of biological micro-arrays of use.Genetic chip is meant thousands of dna probes is placed on the solid phase carrier by the certain position point, by molecular hyridization, target molecule is analyzed again.Biology/chemical microarray and technology thereof are with it fast, in a large number, characteristic is that the research in fields such as life science, medical science pharmacy, agricultural provides revolutionary means accurately.
The manufacturing technology of the genetic chip that uses has contact-type liquid transfer method, ink-jet method, in-situ synthesis etc. at present.In-situ synthesis has been successfully applied to short-chain nucleic acids chip (Southern etc., United States Patent (USP) 5,770,367; 5,770,637; 5,436,327.Pirrung etc., United States Patent (USP) 5,143,854.Fodor, United States Patent (USP) 5,744,305; 5,800,992.Winkler etc., United States Patent (USP) 5,384,261).The shortcoming of this method is that the microarray that can't be used for big molecule (as the DNA of long-chain) is made, and this method is relatively more expensive in addition and operation difficulty (United States Patent (USP) 6,101,649).Ink-jet method and other non-contact type liquid transfer methods also can be used for processing biology/chemical microarray (Brennan, United States Patent (USP) 5,474,796; Tisone, United States Patent (USP) 5,741,554; Hayes etc., United States Patent (USP) 5,658,802), be particularly useful for the sample of particular viscosity and other physical characteristicss, but be not suitable for several samples or unknown sample (United States Patent (USP) 5,927,947; 6,112,605), and this method has its inherent weak point, and it can't be made highdensity microarray and be not easy to control the quality of microarray (United States Patent (USP) 6,101,649).Contact-type liquid transfer method is present most widely used microarray method for making.The cardinal principle of this method is that thousands of points contact solid phase carriers after utilizing aciculiform liquid transfer device (spotting needle) to be stained with/to draw probe solution, thereby makes the chip that contains thousands of nucleic acid probe points.The major defect of this method is that expensive needle point rapid wear injures sampling point homogeneity relatively poor (Chinese patent CN1302904), though people have designed many kinds of spotting needles (United States Patent (USP) Augenlicht4,981,783; Drmanac etc., United States Patent (USP) 5,525,464; Roach, United States Patent (USP) 5,770,151; Brown etc., United States Patent (USP) 5,807,522; Chinese patent CN1302904) remedies these shortcomings, utilize this method can make highdensity chip, but its physical construction makes the number of this method spotting needle seldom (be generally 32 pins), efficient is restricted, make high-density biology/chemical microarray and need the long time, when especially point is put different sample on a chip, clean and dry up needle point and need a large amount of time, therefore can not satisfy the requirement (United States Patent (USP) 6 of more and more highdensity chip development trend, 245,297).
The present invention aim to provide a kind of accurate CONTROL VOLUME surface tension driving liquid stream chipization high-density micro-array ultramicron liquid transfer device---micro-array liquid shifts chip (microarrayer chip), and it can satisfy the requirement of current making biology/chemical microarray:
1, high density (diameter of each probe sample point is little, and the sample on the unit area is counted and wanted many);
2, sample spot good uniformity (this unanimity of probe molecule base of the diameter of every bit and every bit; Sample spot is accurately located);
3, high-level efficiency (mechanical action is transferred to sample on the biochip and counted and want many each time, and the cost of liquid transfer process is low, is convenient to make on a large scale biology/chemical chip);
4, devices with low cost (equipment is simple, and it is low and can disposablely use that micro-array liquid shifts chip cost, avoids cross pollution).
The high-density micro-array liquid transferring equipment of the chipization of said surface tension driving liquid stream is provided with a sheet carrier, the liquid that chip carrier is provided with the microarray ultramicron shifts combination, said combination comprises liquid storing part, liquid transfer head and microchannel, liquid storing part can be tank body, liquid storage tank, reservoir or liquid storage face etc. are used for the storaging liquid sample; Liquid transfer head (or claiming sampling head) is used for the transfer liquid sample; Said microchannel UNICOM is used for replenishing sample solution by liquid storing part to the liquid transfer head between liquid storing part and liquid transfer head.
The volume of liquid storing part (as tank body, liquid storage tank, reservoir or liquid storage face etc.) can be the liquid transfer head and carries 5000~10 times of the ultramicron volume that presets, is preferably 1000~100 times.The storing solution of different fluid samples (can be to receive and rise to microlitre) is stored in to array the liquid storing part of big quantity.Each liquid transfer head is carried the different sample solutions of the ultramicron volume that presets, and said ultramicron volume is presetted by the geometric parameter of liquid transfer head, can be 1 skin liter~100 and receives the volume that rises, and is preferably 100 skin liter~1 and receives liter.The liquid transfer head can be provided with the liquid storing part pairing, and the liquid transfer head can be made as tubulose, and is poroid, and curved surface or plane can be located in the chip carrier or the bottom surface of chip carrier, can be located at the side or the bottom of liquid storing part.
The effect of the microchannel of UNICOM's liquid storing part and liquid transfer head is to replenish sample solution by liquid storing part to the liquid transfer head.The shape of passage can be long and narrow open shape or enclosed shape, can establish filling material in the passage.
The shape of microchannel can be long and narrow open shape or enclosed shape, can establish filling material in the passage, porous packing preferably, and its parameter is carried the size of the ultramicron volume that presets by the liquid transfer head and is decided.
Thousands of groups the liquid transfer combination sum that is integrated in to said array on the chip carrier can be 10 1~10 5(depending on the needs).The area of the chip carrier of chipization shifts the combination sum on liquid to be decided, and can be made as 1~100cm 2Level.
The material of chip carrier can be macromolecular material, semiconductor material, metal or silicate material etc.
Said micro-array liquid shifts the making of chip can adopt photoetching technique, Laser Processing, molding or die casting etc.
The present invention can be added to hundreds and thousands of kinds required sample liquid respectively micro-array liquid in use and shift in each liquid storing part of chip.Flow into the corresponding liquid transfer head by the microchannel.Each liquid transfer head is carried the Asia that presets and is received the different sample solutions (can be DNA, protein, the solution of chemical/biological reagent/sample or the like) that rise volume.When accepting the carrier that liquid shifts, for example blank (or part is blank) biochip (or nylon membrane) and above-mentioned micro-array liquid shift that chip is placed abreast face-to-face and mutually near and when contacting, the entrained Asia of being scheduled to of thousands of array liquid transfer head is received the different samples that rise volume and is all just transferred to the former and form the microarray sample from the latter under surface tension effects basically.The two disengages then.(action of above-mentioned " placing face-to-face abreast and mutual close and contact " can be implemented aligning by the automation of sequencing, and also a step finishes).The liquid transfer head loses entrained Asia and receives after the upgrading volume sample, and every group of deposit sample liquid received the sample solution that rises volume via the microchannel to the additional Asia that presets of this group liquid transfer head automatically under surface tension effects.Changing another accepts to repeat said process behind the liquid transfer vector.It is hundreds and thousands of time to circulate, and then the deposit sample liquid of thousands of different cultivars can be received by the Asia that presets at every turn to rise volume and transfer to hundreds and thousands of and accept on the liquid transfer vector.
Compared with prior art, advantage of the present invention is:
1, this device adopts high density, the chip micro-array liquid shifts chip structure, its structure is not only very simple, and the microstream process that shifts of the micro liquid of whole device can an abutment surface tension force effect, therefore the distance (pitch) that adjacent liquid shifts between the combination can be very near, the liquid that each device is arranged shifts combination can thousands of groups, the sample kind number that each step shifts far surpasses existing technology, that is to say, the storing solution of thousands of different cultivars can be received by the Asia that presets at every turn risen volume and transfer on hundreds and thousands of the biochips, improve the efficient of preparation biochip greatly.
2, because the structure of the micro-array liquid of surperficial micro liquid transfer device transfer chip is very simple, and the microstream process of whole device can an abutment surface tension force effect, therefore manufacturing cost of the present invention is very low, might avoid washing and cross pollution as disposable product.
3, because the entrained different samples of liquid transfer head are the different sample solutions that preset volume.Under surface tension effects, all transfer to basically on the biochip (for example nylon membrane), so the reappearance of transfer volume is better at every turn.
4, because the entrained different samples of liquid transfer head are the volume that presets, this volume depends mainly on the parameter of the liquid transfer head structure of device, therefore can be set at the Asia and receive and rise or skin rises volume, consequently can hold more more intensive array points on each biological core.
In sum, the characteristic of the present invention's, pinpoint accuracy high-speed with it, high density and chipization is that the scientific research and the technological development in fields such as life science, medical science pharmacy, agricultural provides revolutionary means.
Fig. 1 is the structural representation of the embodiment of the invention.
As shown in Figure 1, select sheet metal as chip carrier 1 of the present invention, its size is elected long 100mm as, wide 40mm, thick 1mm.Utilize photoetching technique to establish circular liquid storage tank 2 at the glass sheet upper surface, its radius is 0.3mm, high 0.8mm; Establish cylindrical liquid transfer head 3 at liquid storage tank 2 sides in addition, the radius of liquid transfer head 3 is 0.05mm.Liquid storage tank 2 and the 3 pairing array designs of liquid transfer head, the distance between the adjacent liquid storage tank can be made as 0.4mm.Establish long and narrow closed microchannel 4 UNICOMs between the upper port of liquid storage tank 2 and liquid transfer head 3.

Claims (10)

1、表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于设有一片状载体,片状载体上设有微阵列超微量的液体转移组合,所说的组合包括储液部、液体转移头和微通道,所说的微通道联通于储液部与液体转移头之间。1. A chip-based high-density microarray liquid transfer device with surface tension driven liquid flow, characterized in that it is provided with a sheet-shaped carrier, and the sheet-shaped carrier is provided with a micro-array ultra-micro-quantity liquid transfer combination. The combination includes a liquid storage part, liquid transfer head and microchannel, said microchannel communicates between the liquid storage part and the liquid transfer head. 2、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于所说的片状载体的面积为1~100cm22. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1, characterized in that the area of the sheet-shaped carrier is 1-100 cm 2 . 3、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于所说的储液部为储液体,储液池,储液槽或储液面。3. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1, characterized in that said liquid storage part is a liquid storage, a liquid storage pool, a liquid storage tank or a liquid storage surface . 4、如权利要求1或4所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于所说的储液部的体积为液体转移头携带预设定的超微量体积的5000~10倍。4. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1 or 4, characterized in that the volume of the liquid storage part is such that the liquid transfer head carries a preset ultra-micro amount 5000 to 10 times the volume. 5、如权利要求4所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于所说的储液部的体积为液体转移头携带预设定的超微量体积的1000~100倍。5. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow as claimed in claim 4, characterized in that the volume of the liquid storage part is that the liquid transfer head carries a preset ultra-micro volume. 1000-100 times. 6、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于所说的储液部的储备液为纳升至微升级。6. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1, characterized in that the stock liquid in the liquid storage part is nanoliter to microliter. 7、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于液体转移头与储液部配对设置,液体转移头设为管道,孔,曲面或平面,设在储液部的旁侧或底部。7. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1, characterized in that the liquid transfer head is paired with the liquid storage part, and the liquid transfer head is set as a pipe, hole, curved surface or The plane is arranged on the side or bottom of the liquid storage part. 8、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于每一个液体转移头携带预设定的超微量体积由液体转移头的几何参数预设定,为1皮升~100纳升。8. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1, characterized in that each liquid transfer head carries a preset ultra-micro volume which is preset by the geometric parameters of the liquid transfer head The setting is 1 picoliter to 100 nanoliters. 9、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于通道形状为开放形或封闭形。9. The surface tension-driven liquid flow chip-based high-density microarray liquid transfer device according to claim 1, characterized in that the shape of the channel is open or closed. 10、如权利要求1所述的表面张力驱动液流的芯片化的高密度微阵列液体转移装置,其特征在于在微通道内设填充物。10. The chip-based high-density microarray liquid transfer device with surface tension driven liquid flow according to claim 1, characterized in that fillers are arranged in the microchannels.
CN 02126729 2002-07-12 2002-07-12 Surface tension driving liquid flow chiplized high-density micro-array liquid transferring equipment Expired - Fee Related CN1195984C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 02126729 CN1195984C (en) 2002-07-12 2002-07-12 Surface tension driving liquid flow chiplized high-density micro-array liquid transferring equipment

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 02126729 CN1195984C (en) 2002-07-12 2002-07-12 Surface tension driving liquid flow chiplized high-density micro-array liquid transferring equipment

Publications (2)

Publication Number Publication Date
CN1467499A true CN1467499A (en) 2004-01-14
CN1195984C CN1195984C (en) 2005-04-06

Family

ID=34143376

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 02126729 Expired - Fee Related CN1195984C (en) 2002-07-12 2002-07-12 Surface tension driving liquid flow chiplized high-density micro-array liquid transferring equipment

Country Status (1)

Country Link
CN (1) CN1195984C (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100348324C (en) * 2004-11-10 2007-11-14 厦门大学 Multichannel array micro liquid transferrer
CN102109858A (en) * 2010-12-03 2011-06-29 清华大学 Motion control device based on liquid surface tension
CN108767092A (en) * 2018-07-17 2018-11-06 佛山市国星半导体技术有限公司 A kind of method and apparatus of batch transfer MicroLED chips
CN113314453A (en) * 2021-05-20 2021-08-27 湘潭大学 Micro-LED transferring method and device
CN113937049A (en) * 2020-06-29 2022-01-14 重庆康佳光电技术研究院有限公司 Microfluidic chip and its manufacturing method, transfer head and its manufacturing method

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100538321C (en) * 2006-12-30 2009-09-09 清华大学 A microfluidic chip device for liquid surface tension measurement

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100348324C (en) * 2004-11-10 2007-11-14 厦门大学 Multichannel array micro liquid transferrer
CN102109858A (en) * 2010-12-03 2011-06-29 清华大学 Motion control device based on liquid surface tension
CN102109858B (en) * 2010-12-03 2015-08-12 清华大学 Based on the motion control device of surface tension of liquid
CN108767092A (en) * 2018-07-17 2018-11-06 佛山市国星半导体技术有限公司 A kind of method and apparatus of batch transfer MicroLED chips
CN108767092B (en) * 2018-07-17 2024-05-31 佛山市国星半导体技术有限公司 Method and device for transferring MicroLED chips in batches
CN113937049A (en) * 2020-06-29 2022-01-14 重庆康佳光电技术研究院有限公司 Microfluidic chip and its manufacturing method, transfer head and its manufacturing method
CN113314453A (en) * 2021-05-20 2021-08-27 湘潭大学 Micro-LED transferring method and device

Also Published As

Publication number Publication date
CN1195984C (en) 2005-04-06

Similar Documents

Publication Publication Date Title
US8999726B2 (en) Microfluidic interface for highly parallel addressing of sensing arrays
US7025935B2 (en) Apparatus and methods for reformatting liquid samples
US7390463B2 (en) Microcolumn-based, high-throughput microfluidic device
US20190118173A1 (en) Nanoliter array loading
US8231844B2 (en) Method and device for manipulating liquids in microfluidic systems
US8029744B2 (en) Method of liquid droplet formation and transport apparatus therefor and particle manipulating apparatus
JP2003500205A (en) Multi-fluid sample processor and system
CN104492508B (en) A kind of ultramicron liquid drop control device and method based on liquid residue
US6399396B1 (en) Compressed loading apparatus and method for liquid transfer
He et al. Technologies and applications in micro-volume liquid handling
US7008788B2 (en) Containers for supports comprising biopolymers
CN103394380A (en) High-flux trace liquid sample distribution device and use method
Rose Microfluidic technologies and instrumentation for printing DNA microarrays
CN112292206A (en) Microfluidic probe head with suction column
CN1467499A (en) Surface tension-driven liquid flow on a chip high-density microarray liquid transfer device
US20030152957A1 (en) Probe-immobilized reaction arrays
CN1422175A (en) Method and device for producing biopolymer arrays
US10761104B2 (en) Systems and methods for transferring liquids
CN1825121A (en) Plastic chip
TW201236760A (en) High-throughput assay methods and articles
KR100320752B1 (en) automated microarray of samples
JP2002116205A (en) Liquid discharge device as well as method and apparatus for manufacture of microarray using it
CN100348324C (en) Multichannel array micro liquid transferrer
Vetter Miniaturization for drug discovery applications
JPWO2004104584A1 (en) Biologically related substance inspection method, fluid transfer device and fluid transfer method therefor

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20050406

Termination date: 20140712

EXPY Termination of patent right or utility model