MICROFLUIDIC SYSTEM FOR TRAPPING AND DETECTION OF A BIOLOGICAL ENTITY IN A SAMPLE

• US 20110117577A1
• Filed: 10/20/2010
• Published: 05/19/2011
• Est. Priority Date: 10/20/2009
• Status: Abandoned Application

• Current Assignee: Agency For Science Technology and Research
• Original Assignee: Agency For Science Technology and Research
• Inventors: Lim, Huimin, Lee, Kokchuan, Ji, Hongmiao, Reboud, Julien
• Application Number:
  US12/908,553
• Publication Number:
  US 20110117577A1
• Time in Patent Office: Days
• US Class Current: 435/7.23
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2400/0424 Dielectrophoretic forces
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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: B03C 1/01 by addition of magnetic adjuvants
• CPC Class Codes: B03C 1/0332 using permanent magnets
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: B03C 5/026 using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 15/1031 by measuring electrical or magnetic effects
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing

Abstract

According to embodiments of the present invention, a microfluidic system for detecting a biological entity in a sample volume is provided. The microfluidic system includes: an inlet configured to receive the sample volume; at least one microchannel in fluid communication with the inlet; a magnetic trapping region comprising the at least one microchannel; at least one detection region in fluid communication with the magnetic trapping region for detecting the biological entity to be detected; and at least one outlet in fluid communication with the at least one detection region.

Claims

1. A microfluidic system for detecting a biological entity in a sample volume, the microfluidic system comprising:

an inlet configured to receive the sample volume;

at least one microchannel in fluid communication with the inlet;

a magnetic trapping region comprising the at least one microchannel;

at least one detection region in fluid communication with the magnetic trapping region for detecting the biological entity to be detected; and

at least one outlet in fluid communication with the at least one detection region.

2. The microfluidic system according to claim 1, wherein the at least one microchannel comprises a shape selected from the group consisting of a serpentine shape, a meander shape, a spiral shape and any combination thereof.

3. The microfluidic system according to claim 2, wherein the at least one detection region comprises a microelectrode array.

4. The microfluidic system according to claim 3,

wherein the microelectrode array comprises a plurality of electrodes;

and

wherein each of the plurality of electrodes has a dimension smaller than 4000 μ

m.

5. The microfluidic system according to claim 3, wherein the microelectrode array comprises sensor electrodes.

6. The microfluidic system according to claim 3, wherein a width of the at least one microchannel in the magnetic trapping region is relatively larger than a width of the at least one microchannel outside the magnetic trapping region.

7. The microfluidic system according to claim 6, further comprising:

a trapping chamber comprising the magnetic trapping region; and

a detection chamber comprising the at least one detection region.

8. The microfluidic system according to claim 7, wherein a volume of the detection chamber is approximately ten times larger than a volume of the trapping chamber.

9. The microfluidic system according to claim 1, wherein the magnetic trapping region is configured to reduce a flow rate in the at least one microchannel such that a magnetic force at the magnetic trapping region is configured to trap the biological entity.

10. The microfluidic system according to claim 1, further comprising:

at least one magnet;

wherein the at least one magnet is movably arranged, such that the at least one magnet in a first position is configured to trap the biological entity in the magnetic trapping region and in a second position is configured to release the biological entity.

11. The microfluidic system according to claim 1, wherein the biological entity is selected from the group consisting of a rare biomarker, a cell, a eukaryotic cell, a prokaryotic cell, a mammalian cell, a yeast cell, a tumour cell, a circulating tumour cell, a progenitor cell, an endothelial progenitor cell, a fetal cell, an organelle, a virus particle, a biopolymer, a polypeptide, a nucleic acid, a lipid, an oligosaccharide, and any combination thereof.

12. A microfluidic arrangement, comprising

a microfluidic system for detecting a biological entity in a sample volume, the microfluidic system comprising:

an inlet configured to receive the sample volume;

at least one microchannel in fluid communication with the inlet;

a magnetic trapping region comprising the at least one microchannel;

at least one detection region in fluid communication with the magnetic trapping region for detecting the biological entity to be detected; and

at least one outlet in fluid communication with the at least one detection region; and

a microchip being formed on or in the microfluidic system in a monolithically integrated manner.

13. The microfluidic arrangement according to claim 12, wherein the microchip comprises a capping layer.

14. An assembly for detecting a biological entity in a sample volume, the assembly comprising:

a microfluidic system for detecting a biological entity in a sample volume, the microfluidic system comprising;

an inlet configured to receive the sample volume;

at least one microchannel in fluid communication with the inlet;

a magnetic trapping region comprising the at least one microchannel;

at least one detection region in fluid communication with the magnetic trapping region for detecting the biological entity to be detected; and

at least one outlet in fluid communication with the at least one detection region; and

a magnetic labeling device configured to label the biological entity to be detected with magnetic beads;

wherein the magnetic labeling device is in fluid communication with the microfluidic system to supply the labeled biological entity to the microfluidic system.

15. A method for detecting a biological entity in a sample volume using a microfluidic system for detecting a biological entity in a sample volume, the microfluidic system comprising:

an inlet configured to receive the sample volume;

at least one microchannel in fluid communication with the inlet;

a magnetic trapping region comprising the at least one microchannel;

at least one detection region in fluid communication with the magnetic trapping region for detecting the biological entity to be detected; and

at least one outlet in fluid communication with the at least one detection region;

the method comprising;

providing the sample volume to the at least one microchannel via the inlet;

trapping the biological entity to be detected at the magnetic trapping region via a movably arranged magnet, wherein the magnetic trapping region is in fluid communication with the at least one microchannel;

removing the magnet from the magnetic trapping region;

transferring the biological entity from the magnetic trapping region to the at least one detection region; and

detecting the biological entity in the at least one detection region.

16. The method according to claim 15, wherein the method comprises a process selected from the group consisting of dielectrophoresis, capturing by antibodies, impedance measuring, and any combination thereof.

17. A method for manufacturing a microfluidic system, the method comprising:

providing a substrate;

thinning the substrate at a predetermined portion of the substrate from a first surface of the substrate;

forming a magnetic trapping region in a vicinity of the thinned portion of the substrate on a second surface of the substrate opposite the first surface;

forming at least one microchannel in fluid communication with the magnetic trapping region on the substrate;

forming at least one detection region in fluid communication with the magnetic trapping region;

forming at least one electrode in the at least one detection region; and

providing a capping layer on the substrate.

18. The method according to claim 17, wherein thinning the substrate is carried out by means of etching.

19. The method according to claim 17, wherein forming the at least one microchannel on the substrate is carried out using a photoresist, wherein the photoresist is spin-coated on the substrate and patterned using a lithography process.

20. The method according to claim 17, wherein forming the at least one electrode on the at least one detection region is carried out using metal deposition and patterning.