Manipulation of microparticles in microfluidic systems

• US 10,138,517 B2
• Filed: 06/06/2017
• Issued: 11/27/2018
• Est. Priority Date: 02/23/1999
• Status: Expired due to Fees

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Mehta, Tammy Burd, Kopf-Sill, Anne R., Parce, J. Wallace, Chow, Andrea W., Bousse, Luc J., Knapp, Michael R., Nikiforov, Theo T., Gallagher, Steve
• Primary Examiner(s): Gross, Christopher M
• Application Number:
  US15/615,469
• Publication Number:
  US 20170356040A1
• Time in Patent Office: 539 Days
• Field of Search: None
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2525/186 incorporating a non-extendable or blocking moiety
• CPC Class Codes: C12Q 2527/125 Specific component of sample, medium or buffer
• CPC Class Codes: C12Q 2535/101 Sanger sequencing method, i.e. oligonucleotide sequencing using primer elongation and dideoxynucleotides as chain terminators
• CPC Class Codes: C12Q 2563/173 staining/intercalating agent, e.g. ethidium bromide
• CPC Class Codes: C12Q 2565/629 : being a microfluidic device
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/00574 : Means for distributing beads
• CPC Class Codes: G01N 27/44756 : Apparatus specially adapted therefor
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]

Abstract

An array of transportable particle sets is used in a microfluidic device for performing chemical reactions in the microfluidic device. The microfluidic device comprises a main channel and intersecting side channels, the main channel and side channels forming a plurality of intersections. The array of particle sets is disposed in the main channel, and the side channels are coupled to reagents. As the particle sets are transported through the intersections of the main channel and the side channels, reagents are flowed through the side channels into contact with each array member (or selected array members), thereby providing a plurality of chemical reactions in the microfluidic system.

Claims

1. A method of modifying flow in a microchannel, the method comprising:

flowing a first particle set into the microchannel;

performing a first assay in the microchannel;

moving the first particle set within the microchannel and flowing a second particle set stacked against the first particle set into the microchannel, thereby altering the hydrodynamic resistance in the microchannel; and

,

performing a second assay in the microchannel.

2. The method of claim 1, the method further comprising altering the surface charge on the first particle set, thereby modifying the zeta potential of the first particle set.

3. The method of claim 1, the method further comprising altering the surface charge on the first particle set, thereby modifying the zeta potential of the first particle set, wherein the zeta potential is altered in response to the results of the first assay or the second assay in the microchannel.

4. The method of claim 1, the method further comprising altering the surface charge on the first particle set, thereby modifying the zeta potential of the first particle set, wherein the zeta potential is altered in response to the results of the first assay or the second assay in the microchannel, wherein the results of the first assay or the second assay are detected using a system comprising a microprocessor and the hydrodynamic resistance or zeta potential are altered in response to a signal from the system.

5. The method of claim 1, wherein either the first assay or the second assay comprises contacting a reagent with a member of the first particle set or the second particle set respectively, or with a member of a third particle set.

6. The method of claim 1, wherein the first particle set acts as a matrix to prevent passage of the second particle set.

7. The method of claim 1, wherein the first particle set comprises particles of a dimension such that particles of the second particle set cannot pass therebetween.

8. The method of claim 1, wherein at least one of the first particle set and the second particle set comprise one of magnetic particles and affinity particles.

9. The method of claim 1, wherein at least one of the first particle set and the second particle set comprise at least one of polymer beads, silica beads, silicon beads, clay beads, ceramic beads, glass beads, magnetic beads, metallic beads, inorganic compound beads, organic compound beads, magnetic particles and affinity particles.

10. The method of claim 1, wherein at least one of the first particle set and the second particle set comprise at least one material comprising a linking chemistry for linking molecules thereto.

11. A method of performing assay in a microchannel, the method comprising:

stacking a first particle set against a second particle set;

flowing the first particle set into the microchannel;

performing a first assay in the microchannel;

moving the first particle set within the microchannel and flowing the second particle set into the microchannel, thereby altering the hydrodynamic resistance in the microchannel; and

,

performing a second assay in the microchannel.

12. The method of claim 11, further comprising controlling the moving according to results of the first assay.

13. The method of claim 11, wherein steps of the second assay are selected based on the results of the first assay.

14. The method of claim 11, further comprising controlling the moving according to software feedback control.