Microbead-filled microsystem and production method thereof

• US 20060068450A1
• Filed: 11/12/2003
• Published: 03/30/2006
• Est. Priority Date: 11/13/2002
• Status: Abandoned Application

• Current Assignee: Commissariat a L'Energie Atomique (AES Corporation)
• Original Assignee: Energies Alternatives Commissariat A L'Energie Atomique et AUX
• Inventors: Caillat, Patrice, Combette, Philippe, Mittler, Frederique
• Application Number:
  US10/533,947
• Publication Number:
  US 20060068450A1
• Time in Patent Office: Days
• US Class Current: 435/7.900
• CPC Class Codes: B01D 15/22 relating to the construction of the column
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/00747 Catalysts
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B81B 2201/051 Micromixers, microreactors
• CPC Class Codes: C40B 30/08 by measuring catalytic activity
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/18 Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize

Abstract

The invention relates to a micro-system intended to receive beads and to obtain a precise positioning of the beads at preset locations in the micro-system. This micro-system comprises a tank that has a cavity, the cavity being fitted with blocking elements allowing the beads to be ordered and stacked in the interstices between the blocking elements, the interstices constituting the preset locations. It also comprises a cap anchored hermetically to the tank and input means and output means allowing a fluid to flow in the cavity. The invention also relates to the implementation and use of the bead-filled micro-system.

Claims

1. A micro-system for receiving beads and obtaining a precise positioning of said beads at preset locations in said micro-system, comprising:

a tank that has a cavity which is fitted with blocking elements having the form of columns, said blocking elements allowing to block beads in interstices between said blocking elements in an ordered way and in stacks, said interstices constituting said preset locations,

a cap hermetically sealing said tank,

and import means and output means allowing a fluid to flow in said cavity.

2. The micro-system according to claim 1, wherein said blocking elements are integral with the bottom of said cavity or said cap.

3. The micro-system according to claim 1, wherein said beads all have the same diameter, and said blocking elements are evenly arranged in a two-dimensional network.

4. The micro-system according to claim 1, wherein said micro-system having to receive beads of different diameters, said blocking elements are distributed so as to obtain a positioning of said beads as a function of their diameters.

5. The micro-system according to claim 4, wherein said blocking elements are distributed so as to constitute wells intended to receive beads of a first preset diameter and spaces between the wells intended to receive beads of a second preset diameter.

6. The micro-system according to claim 3, wherein said two-dimensional network is a hexagonal mesh.

7. The micro-system according to claim 3, wherein said two-dimensional network is a square mesh.

8. The micro-system according to claim 1, wherein said blocking elements have a transverse cross-section of a shape selected from among discs, ellipses and polygons.

9. The micro-system according to claim 8, wherein said blocking elements have a transverse cross-section in the shape of a hexagon.

10. The micro-system according to claim 1, wherein said blocking elements are of a height that allows at least two beads to be stacked.

11. A micro-reactor comprising the micro-system according to claim 1 and beads of one and the same diameter and with the same function, fitted between said blocking elements.

12. A micro-reactor comprising the micro-system according to claim 1 and beads, of the same diameter but functionalised differently, fitted between said blocking elements.

13. A micro-reactor comprising the micro-system according to claim 1 and beads, with the same function but of different diameters, fitted between said blocking elements.

14. A micro-reactor comprising the micro-system according to claim 1 and beads, of different diameters and functions, fitted between said blocking elements.

15. A process for making the micro-system according to claim 1, comprising the following stages:

forming, by micro-machining a substrate, the tank that has said cavity fitted with said blocking elements,

supplying a cap intended to seal said cavity of said tank hermetically, and

forming said fluid import means and said output means by micro-machining said tank and/or said cap.

16. The process according to claim 15, wherein said micro-machining is carried out by a process of dry or wet etching a material.

17. The process according to claim 15, wherein said micro-machining is carried out by impression moulding process.

18. The process according to claim 15, wherein said micro-machining is carried out by photolithography process.

19. A process for obtaining the micro-reactor according to claim 11, comprising filling functionalised beads in suspension in a liquid by sedimentation.

20. A process for obtaining a multi-functional micro-reactor, comprising filling the micro-system according to claim 3 with functionalised beads of one and the same diameter but with different functions, comprising:

for beads functionalised according to a first function, the following stages;

a) placing a cover on said tank leaving accessible the part in which it is wished to place the beads of a first function,

b) filling by sedimentation, and

c) withdrawing said cover,

for beads functionalised according to another function, the repetition, as many times as there are functions remaining, of stages a) to c) with beads of said other function,

sealing said tank with said cap.

21. A process for obtaining a multi-functional micro-reactor by filling the micro-system, according to claim 4, with beads the function of which is related to the diameter of said beads, comprising at least two filling stages, the order of said filling stages corresponding to the decreasing order of the diameter of said beads.

22. A process for implementing a biochemical or biological reaction, comprising flowing a fluid stream in the micro-reactor according to claim 11, so that at least one constituent of said fluid stream reacts with pre-functionalised beads able to produce a chemical, electrochemical, biological or biochemical reaction, and at micro-reactor output(s) a fluid stream is collected that includes product(s) of said reaction.

23. The process according to claim 22, wherein said reaction is a reaction of the substrate enzyme type, said pre-functionalised beads able to produce a biological or biochemical reaction are enzymes, said constituent of the fluid stream is a substrate of the enzyme, and said products of the reaction are products arising from reaction of said enzyme with said substrate.

24. The process according to claim 22, wherein said reaction is an enzymatic digestion reaction by a protease, said pre-functionalised beads able to produce a biological or biochemical reaction are proteases and said constituents of the fluid stream are peptides or proteins and said products of the reaction are peptidic segments.

25. The process according to claim 24, wherein the enzyme is trypsin.