MICROFLUIDIC DEVICE AND METHOD WITH TRAPPING OF SAMPLE IN CAVITIES HAVING LIDS THAT CAN BE OPENED OR CLOSED

• US 20040166577A1
• Filed: 02/24/2003
• Published: 08/26/2004
• Est. Priority Date: 08/23/2000
• Status: Active Grant

• Current Assignee: Robert Otillar
• Original Assignee: Imego Aktiebolag (Government of Sweden)
• Inventors: Schneeberger, Niklaus, Storek, David, Krozer, Anatol, Otillar, Robert P. Jr.
• Granted Patent: US 7,351,592 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/0034 in the shape of a ball or sphere
• CPC Class Codes: B01J 2219/00439 using micromirror arrays
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00822 Metal
• CPC Class Codes: B01J 2219/00828 : Silicon wafers or plates
• CPC Class Codes: B01J 2219/00833 : Plastic
• CPC Class Codes: B01J 2219/00914 : by dielectrophoresis
• CPC Class Codes: B01J 2219/00918 : by adsorption
• CPC Class Codes: B01J 2219/0093 : Electric or magnetic energy
• CPC Class Codes: B01J 2219/00934 : Electromagnetic waves
• CPC Class Codes: B01J 2219/0095 : Control aspects
• CPC Class Codes: B01L 2200/0647 : Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/049 : Valves integrated in closure
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2400/043 : magnetic forces
• CPC Class Codes: B01L 2400/0433 : vibrational forces
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/50853 : with covers or lids
• CPC Class Codes: B03C 1/035 : Open gradient magnetic separators, i.e. separators in which the gap is unobstructed, characterised by the configuration of the gap
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 33/54333 : Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction

Abstract

Method and arrangement (10, 20) for preparing samples (15, 27) submergible in a liquid medium. The arrangement includes a carrier structure (11). The carrier includes a device (13, 23) for controllable generation of a magnetic field through influence of a control signal to attract at least part of the at least first and second type of samples (15, 27) towards specific locations on the carrier when connected to a first control signal and to repel at least one of the first or second type of samples when connected to a second control signal.

Claims

1. A liquid medium submergible sample preparing arrangement suitable for enhancing detection of different samples comprising at least first or second type of samples, said arrangement comprising:

a carrier structure including a device for controllable generation of a magnetic field through influence of a control signal to attract at least part of said at least first and second type of samples towards specific locations on said carrier when connected to a first control signal and to repel at least one of said first or second type of samples when connected to a second control signal.

2. The arrangement as recited in claim 1, wherein said device is a magnetically active material.

3. The arrangement as recited in claim 1, wherein said device is made of an electrically conducting material.

4. The arrangement as recited in claim 1, wherein said device is made of aluminum.

5. The arrangement as recited in claim 1, wherein each device, through a conductor, is applied a current of different strength.

6. The arrangement as recited in claim 1, wherein said device is a coil.

7. The arrangement as recited in claim 3, wherein a current amplitude and the number of windings in the coil are proportional to the strength of the magnetic field.

8. The arrangement as recited in claim 1, further comprising a cavity provided in the carrier structure provided as a substrate.

9. The arrangement as recited in claim 8, further comprising a magnetic lid for closing said cavity.

10. The arrangement as recited in claim 9, wherein said bead is directed onto a cavity using external magnets that create magnetic fields counteracting the field created by the material deposited around each cavity.

11. The arrangement as recited in claim 9, wherein said lid is a micro-bead introduced in said liquid medium.

12. The arrangement as recited in claim 1, wherein said particle is attracted to a predetermined cavity when the coil of said cavity is energized by electric current to produce magnetic field of spatial attraction.

13. The arrangement as recited in claim 12, wherein before sealing off the cavity, smaller magnetic particles are attracted into the cavity.

14. The arrangement as recited in claim 1, wherein said sample is a magnetic particle covered with appropriate chemicals.

15. The arrangement as recited in claim 14, wherein said capping is detected by detecting the change in inductance in the control circuit, which produces the attractive magnetic field, whereby the bead acts as a magnetic yoke in a transformer, increasing the inductance.

16. The arrangement as recited in claim 1, further comprising means for detection of changes of inductance when a magnetic particle passes through the opening into or out of a cavity.

17. The arrangement as recited in claim 16, wherein said detection is determined using the direction of externally controlled magnetic field by one of (1) changing the direction of the electric current flowing through a coil and (2) flipping an external magnetic.

18. The arrangement as recited in claim 16, wherein said particle contains particular molecular coating, which reacts with the liquid in that cavity or with the coating adsorbed on the walls of the cavity.

19. The arrangement as recited in claim 8, wherein said substrate is made of silicon, Si, or of Si-compound, such as Si-oxide Si-nitride or Si-carbide, or combinations thereof, or a suitable polymer, such as polyethylene, polyethylene glycol, polyethylene oxide, fluorine containing a polymer (PTFE BTeflon), or silicon containing a polymer.

20. The arrangement as recited in claim 1, further comprising a carrier substrate.

21. The arrangement as recited in claim 1, further comprising a member for generating acoustic waves and said device on one of (1) a substrate and (2) a carrier.

22. The arrangement as recited in claim 21, wherein said device and the member for generating acoustic waves are covered with an insulating layer constituting said carrier.

23. The arrangement as recited in claim 21, wherein, on the insulating layer, a combination of receptor-bead of a magnetizable material is attached.

24. The arrangement as recited in claim 23, wherein a sample is provided with a magnetic portion attractive toward the receptor.

25. The arrangement as recited in claim 24, wherein said combination of receptor-bead attenuates the acoustic wave stronger than receptors attached to the insulating layer.

26. The arrangement as recited in claim 21, wherein said surface of the insulating layer is inert to receptors, and the receptor-bead combination is attached to the surface by magnetic forces acting on the bead.

27. The arrangement as recited in claim 24, further comprising a matrix of interdigitated electrodes, whereby a certain number of electrode pairs constitute a single site and a capacitor.

28. The arrangement as recited in claim 27, wherein each site of the matrix is prepared differently, by using different agents, and by directing beads, with specific molecules attached to them, to said sites using magnetic field, or withdrawing particles from these sites, the dielectric constant of a layer close to the surface is perturbed and large changes of the capacitance of the device, compared to attachment of only a molecule, is detected.

29. A method for analyzing different samples in an analysis arrangement in a fluid medium, said samples being provided with magnetic members, the method comprising:

providing an arrangement comprising a carrier structure, a testing section on said carrier structure provided with a magnetic field generator upon reception of a control signal, wherein said testing section is provided with a test material reactive to at least one type of said samples; and

attracting said different samples to said testing section by generating a magnetic attraction force, and after reaction, repelling samples not being of said one type.

30. The method as recited in claim 29, said generator being applied a current of different strength.

31. The method as recited in claim 30, wherein said arrangement is provided with a cavity in a substrate.

32. The method as recited in claim 31, further comprising arranging a magnetic lid for closing said cavity.

33. The method as recited in claim 32, further comprising directing said bead onto a cavity using external magnets that create magnetic fields counteracting the field created by the material deposited around each cavity.

34. The method as recited in claim 29, further comprising attracting smaller magnetic particles into the cavity before sealing off the cavity.

35. The method as recited in claim 29, wherein said sample is a magnetic particle covered with an appropriate chemical.

36. The method as recited in claim 31, further comprising detecting changes of inductance when a magnetic particle passes through the opening into or out of a cavity.

37. The method as recited in claim 36, further comprising determining said indication using the direction of externally controlled magnetic field by one of (1) changing the direction of the electric current flowing through a coil and (2) flipping an external magnetic.

38. The method as recited in claim 31, wherein given a known number of samples in each cavity and a density of respective coatings, quantitative data on the number of reaction between the coating on a wall of the cavity and the coating on a small sample is obtained by counting the number of samples.