Microfluidic device and uses thereof

• US 9,156,037 B2
• Filed: 01/15/2010
• Issued: 10/13/2015
• Est. Priority Date: 01/15/2009
• Status: Active Grant

• Current Assignee: Charles Stark Draper Laboratory Incorporated, Children's Medical Center Corporation
• Original Assignee: Charles Stark Draper Laboratory Incorporated, Children's Medical Center Corporation
• Inventors: Yung, Chong Wing, Ingber, Donald E., Fiering, Jason O., Varghese, Mathew
• Primary Examiner(s): HORLICK, KENNETH R
• Application Number:
  US13/144,572
• Publication Number:
  US 20120149021A1
• Time in Patent Office: 2,097 Days
• Field of Search: 435/6.12, 435/287.1, 435/287.2
• US Class Current: 1/1
• CPC Class Codes: B03C 1/01 by addition of magnetic adjuvants
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/18 Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: G01N 1/40 Concentrating samples
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

A microfluidic device for separating target components from a source fluid includes one or more source channels connected to one or more collection channels by one or more transfer channels. The target components of the source fluid can be magnetic or bound to magnetic particles using a know binding agent. A source fluid containing magnetically bound target components can be pumped through the source channel of the microfluidic device. A magnetic field gradient can be applied to the source fluid in the source channel causing the magnetically bound target components to migrate through the transfer channel into the collection channel. The collection channel can include a collection fluid that is stagnant until a predefined volume of source fluid is processed or a predefined volume of target components accumulate in the collection channel, at which point collection fluid can be pumped into the collection channel to flush the target components out of the collection channel. The target components can be subsequently analyzed for detection and diagnosis.

Claims

1. A microfluidic device comprising:

a source microchannel connected between a source inlet and a source outlet;

a collection microchannel connected between a collection inlet and a collection outlet;

at least one transfer channel connecting the source microchannel and the collection microchannel;

a magnetic field source disposed adjacent to the collection microchannel and configured to apply a magnetic field gradient to a fluid flowing in the source microchannel and to cause target components in the source microchannel to migrate into at least one transfer microchannel, wherein the magnetic field source is positioned over said at least one transfer channel.

2. The microfluidic device of claim 1, further comprising a fluid source connected to the source microchannel and delivering a source fluid to the source channel, the source fluid including target components to be removed from the source fluid;

and a collection fluid source connected to the collection microchannel and delivering a collection fluid to the collection microchannel to fill the collection microchannel and the transfer microchannel, and to flush the target components from the collection microchannel.

3. The microfluidic device of claim 2, wherein the source fluid is a biological fluid selected from the group consisting of blood, plasma, serum, lactation products, amniotic fluids, sputum, saliva, urine, semen, cerebrospinal fluid, bronchial aspirate, perspiration, mucus, liquefied stool sample, synovial fluid, lymphatic fluid, tears, tracheal aspirate, and any mixtures thereof.

4. The microfluidic device of claim 2, wherein the source fluid is a non-biological fluid selected from the group consisting of water, organic solvents, saline solutions, sugar solutions, carbohydrate solutions, lipid solutions, nucleic acid solutions, hydrocarbons, acids, gasoline, petroleum, liquefied foods, gases, and any mixtures thereof.

5. The microfluidic device of claim 2, wherein the collection fluid is selected from the group consisting of water, organic solvents, saline solutions, isotonic saline, a biological fluid, a biocompatible fluid, a biological fluid substitute, sugar solutions, carbohydrate solutions, lipid solutions, nucleic acid solutions, hydrocarbons, acids, gasoline, petroleum, liquefied foods, gases, and any mixtures thereof.

6. The microfluidic device of claim 1, wherein the target component is attracted or repelled by a magnetic field.

7. The microfluidic device of claim 1, wherein the target component is bound to a particle that is attracted or repelled by a magnetic field.

8. The microfluidic device of claim 7, wherein the particle is of size in range from 1 nm to 100 μ

m.

9. The microfluidic device of claim 1, wherein the at least one transfer channel is oriented at an angle of less than 90 degrees to the source microchannel.

10. The microfluidic device of claim 1, wherein the source microchannel and the collection microchannel each have a length of 1 mm to 10 cm, a width of 0.1 mm to 10 mm and a depth of 0.1 mm to 2 mm.

11. The microfluidic device of claim 1, wherein the microfluidic device is fabricated from a biocompatible material.

12. The microfluidic device according to claim 1 further comprising an inline diagnostic device connected to the collection outlet adapted to analyze the target components.

13. A method of separating a target component from a source fluid, the method comprising:

a. providing a microfluidic device having a source microchannel, a collection microchannel, and at least one transfer channel connecting the source microchannel to the collection microchannel, wherein a magnetic field source is positioned over said at least one transfer channel;

b. causing the source fluid to flow through the source microchannel, wherein the source fluid includes the target component to be removed/separated, wherein the target component is attracted or repelled by a magnetic field;

c. providing a collection fluid in the collection microchannel; and

d. applying a magnetic field to the source fluid in the source channel, whereby the target components migrate into the transfer channel.

14. The method of claim 13, further comprising causing the collection fluid to flow through the collection channel, wherein the target components in the collection fluid are removed from the collection microchannel.

15. The method of claim 13, wherein the target component is selected from the group consisting of hormones, cytokines, proteins, peptides, prions, lectins, oligonucleotides, molecular or chemical toxins, cells, bioparticles, pathogens, and any combination thereof.

16. The method of claim 13, further comprising adding particles into the source fluid before or after initiating flow of the source fluid through the source microchannel, wherein the particles are attracted or repelled by a magnetic field gradient.

17. The method of claim 13 further comprising collecting the collection fluid containing the target component in a collection fluid collector, removing at least one target component from the collection fluid collector and analyzing the removed target component using one or more of the processes selected from the group consisting of immunostaining, culturing, PCR, mass spectrometry and antibiotic sensitivity testing.

18. The method of claim 13 further comprising detecting presence of the target component in the collection fluid.

19. A microfluidic system comprising:

a source microchannel connected between a source inlet and a source outlet;

a collection microchannel connected between a collection inlet and a collection outlet;

at least one transfer channel connecting the source microchannel and the collection microchannel;

a magnetic source disposed adjacent to the collection microchannel and configured to apply a magnetic field gradient to a fluid flowing in the source microchannel and to cause target components in the source microchannel to migrate into at least one transfer channel, wherein the magnetic field source is positioned over said at least one transfer channel;

a fluid source connected to the source microchannel, adapted to deliver a source fluid to the source microchannel, the source fluid including target components to be removed from the source fluid, and,

a collection fluid source connected to the collection microchannel, adapted to deliver a collection fluid to the collection microchannel to draw the target components from the transfer microchannel into the collection microchannel and flush the target components from the collection channel

a source pump, connected to the source microchannel, and adapted to pump source fluid into the source microchannel;

a source mixer, connected to the source microchannel and the fluid source, and adapted to mix the source fluid with magnetic particles;

a collection pump, connected to the collection microchannel and the collection fluid source, and adapted to pump collection fluid into the collection microchannel; and

a controller, having a processor and associated memory, and being coupled to the source pump to control the flow of source fluid through the source microchannel and being coupled to the collection pump to control the flow of collection fluid through the collection microchannel.

20. The microfluidic system according to claim 19 further comprising an inline diagnostic device, connected to the collection outlet, adapted to analyze at least one of the target components in the collection fluid.