Coating process for microfluidic sample arrays

a microfluidic array and sample technology, applied in the field of coating process for microfluidic sample arrays, can solve the problems of inability to properly load the microfluidic array with sample, difficult to transfer large fluid samples such as tissue samples stored in 96- or 384-well plates into more efficient high density arrays of nanoliter receptacles, and difficulty in transferring large fluid samples such as small molecule drug candidates, etc., to achieve high surface tension, low surface tension, high surface tension

Inactive Publication Date: 2006-05-18
LIFE TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0024] More specifically, θRA may be determined by looking at each dispenser of the dispenser array using the second camera. The dispensers may approximately form a grid, thus a grid fit algorithm may be used. The grid fit algorithm may return the center of the grid as well as the angle of the grid. The center of the grid may not be the center of rotation. Various algorithms may be in defining the grid fit. One algorithm that may be used minimizes the average amount of error between the real grid and the fitted grid. Another algorithm may minimize the worst case error of any pin on the real grid to the fitted grid.
[0032] In another embodiment of the invention, a method of dispensing a microfluidic sample is provided. The method includes providing an array of dispensers for dispensing the microfluidic sample, and an array of receptacles, each receptacle capable of receiving microfluidic sample from one of the dispensers. At least one of the array of dispensers and the array of receptacles is scanned with a camera for a fiducial reference. The array of dispensers is aligned with the array of receptacles as a function of the fiducial reference such that transfer of sample from the array of dispensers to the array of receptacles is enabled.
[0041] The following provides generalized methods and devices for spatially controlling the surface modifications of an etched surface and is a focus of this invention. One important aspect of the invention is the ability to force load liquids into the OpenArray™ for exchanging fluids that enable the differential coating process. During the manufacture of the OpenArray™ chips, they become uniformly hydrophobic. When loading is attempted to perform chemistry in the through-holes to affect differential coating, a high surface tension fluid will not load the through-holes, and a low surface tension fluid will wet the entire chip. It becomes difficult to perform differential coating a simple way. Therefore, the novel technique of forced loading was invented. The uniformly hydrophobic chip is submerged in a low surface tension co-solvent, such as ethanol. Then the chip is submerged in a high surface tension fluid that contains reagents for the differential chemistry. The high surface tension fluid exchanges and replaces the low surface tension fluid in the wells. When the chip is removed from the high tension fluid, the high surface tension fluid sheets off the exterior coating of the chip, but remains in the through-holes. If the differential coating takes time to complete, and evaporation of the high surface tension fluid from the through-holes is problematic, the chip can then be submerged in an immiscible fluid such as silicone oil or a perfluorinated hydrocarbon. This keeps the high surface tension fluid in the wells while the chemistry or deposition occurs, without evaporation or leakage of the high surface tension fluid onto the exterior of the chip.

Problems solved by technology

However, nanoliter chips require complex time-consuming preparation and processing.
Transferring large collections of fluid samples such as libraries of small molecule drug candidates, cells, probe molecules (e.g., oligomers), and / or tissue samples stored in-older style 96- or 384-well plates into more efficient high density arrays of nanoliter receptacles can be difficult.
Any misalignment of the pins to the through-holes on the chip will result in a failure to properly load the microfluidic array with sample.

Method used

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  • Coating process for microfluidic sample arrays
  • Coating process for microfluidic sample arrays
  • Coating process for microfluidic sample arrays

Examples

Experimental program
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Effect test

example 1

[0260] A surface exposes a carboxylic acid moiety. A solution is prepared with 6-arm polyethylene glycol terminated with —NH2 and —COOH each and (1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride). The carboxylic acid-containing surface is exposed to the solution of polyethylene glycols. If necessary, the solution can be dried on the surface and incubated at elevated temperature to improve the yield of cross-linking between amine and carboxylic acid groups. The resulting surface should show a thick, covalently-attached PEG film.

[0261] Formation of Thick Films of Polyelectrolytes by Layer-To-Layer Adsorption

[0262] A surface is exposed to a solution of polycations and polyanions sequentially. By electrostatic attraction, a film of polycation / polyanion is formed on the surface.

[0263] Differential Coating from Hydroxyl-Terminated Surface

[0264] The exterior and interior surfaces of OpenArray chip are uniformly coated with a film exposing hydroxyl groups. Then, the chip is t...

example 2

[0277] The chip is coated with a hydrophobic silane and a photomask is placed over the chip such that light may only access the interior of the channels. This assembly is exposed to a high energy UV light. The assembly may be subjected to a flow of oxygen to create reactive oxygen species. The combination of light and reactive oxygen cleans the exposed surfaces rendering them hydrophilic and capable of being further derivatized.

example 3

[0278] The chip is coated with a hydrophilic silane such as a PEG silane and a set of photomasks is placed over the chip such that light may only access the exterior surfaces of the array. The array is then exposed to a hydrophobic silane to create the patterned array.

[0279] In such a process, patterned substrates of metal, particularly stainless steel chips, are created through the process of photochemically etching from both sides. This two-sided etching of the through-hole walls creates an hourglass shape for the through-holes, when viewed in cross-section. The resulting “throat” created in the metal chip may be employed for advantage in that one may differentially react, or treat, parts of the channel interior. For example, the top half of the channel could be left hydrophobic, and the bottom half cleaned to become hydrophilic, then optionally coated with a PEG silane. Alternately, a silane with a photoactivated linker moiety may be employed to create reactivity toward a modify...

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Abstract

A differentially coated device for conducting a plurality of nano-volume specified reactions, the device comprising a platen having at least one exterior surface modified to a specified physicochemical property, a plurality of nano-volume channels, each nano-volume channel having at least one interior surface in communication with the at least one exterior surface that is selectively coated with an optionally dissolvable coating agent physisorbed to at least one interior surface, wherein the optionally dissolvable coating agent comprises a coating agent and a first component for the plurality of specified reactions. Methods for preparing and using such devices are also provided, as well as a method of registering a location of a dispenser array in relation to a microfluidic array. A first one of the dispenser array and the microfluidic array is movable in relation to the frame, and the other of the first one of the dispenser array and the microfluidic array is fixed relative to the frame. Quantities related to a vector displacement from the alignment position to a fixed position on the one of the dispenser array and the microfluidic array is determined. The quantities thus determined are used to guide positioning of the dispenser array relative to the microfluidic array.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a regular U.S. application, and claims priority from U.S. Application Ser. No. 60 / 599,217 filed Aug. 4, 2005 entitled Differential Microfluid Coating process; and U.S. Application Ser. No. 60 / 608,231 filed Sep. 9, 2004 entitled “Calibration of Dispensers Relative to a Microfluidic Array,” each of which is incorporated by reference herein.TECHNICAL FIELD [0002] The present invention relates to techniques for transferring small volumes of liquid, and more specifically to calibration of dispensers relative to nanoliter sample volumes in an array. The present invention also relates to processes and the devices for spatially selective chemical modification or coating of the surfaces of a substrate or through-hole array plate, such as may be used in microfluidic or nanofluidic storage and analysis systems or other applications. BACKGROUND ART [0003] Various systems are known for performing a large number of chemical and bi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N5/00
CPCB01L2200/12B01L2200/16B01L3/50857B01L2300/16B01L3/5025B01L3/0244B01J19/0046B01J2219/0059B01J2219/00596B01J2219/00659
Inventor BRENAN, COLIN J.H.CHO, JAMIEGARCIA, JAVIERHESS, ROBERTKANIGAN, TANYA S.KATZ, ARRINKIM, NAMYONGLINTON, JOHNSRIVASTAVA, SHAILESHYODER, KARL
Owner LIFE TECH CORP
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