Combined sorting and concentrating particles in a microfluidic device

Patent metadata

Field	Value
Publication number	US-2017144159-A1
Application number	US-201715425818-A
Country	US
Kind code	A1
Filing date	Feb 6, 2017
Priority date	Nov 3, 2014
Publication date	May 25, 2017
Grant date	—

Abstract

Extracting and concentrating particles from a first fluid sample includes: providing the first fluid sample to a fluid exchange module of a microfluidic device, providing a second fluid sample to the fluid exchange module, in which the first fluid sample and the second fluid sample are provided under conditions such that particle-free portions of the first fluid sample are shifted, and an inertial lift force causes the particles in the first fluid sample to cross streamlines and transfer into the second fluid sample; passing the second fluid sample containing the transferred particles to a particle concentration module under conditions such that particle-free portions of the second fluid sample are shifted, and such that the particles within the second fluid sample are focused to a streamline within the particle concentration module.

First claim

What is claimed is:

1 . A microfluidic device comprising:
a fluid exchange module, the fluid exchange module comprising a corresponding first microfluidic channel and a first array of island structures in the first microfluidic channel, the first array of island structures being arranged in one or more rows that extend along a longitudinal direction of the first microfluidic channel, each island structure in a row being spaced apart from an adjacent island structure in the row to form an opening, wherein the first array of island structures in the fluid exchange module is configured and arranged to shift portions of fluid through the opening between adjacent island structures within a row to a first side of the first array, leaving a remaining portion of the fluid on a second opposite side of the first array, wherein the fluid exchange module further comprises a first fluid exchange output fluidly coupled to the first side of the first array and a second fluid exchange output fluidly coupled to the second opposite side of the first array; and a particle concentration module, the particle concentration module comprising a corresponding second microfluidic channel and a second array of island structures, each island structure in the second array of island structures being spaced apart from an adjacent island structure in the second array of island structures to form an opening, wherein the second array of island structures in each particle concentration module is configured and arranged to shift portions of fluid through the openings between adjacent island structures in the second array of island structures toward a first side of the second array of island structures, and to focus particles contained within the product fluid along one or more streamlines on a second opposite side of the second array of island structures, and wherein the particle concentration module further comprises a first concentration module output fluidly coupled to the second opposite side of the second array of island structures.

2 . The microfluidic device of claim 1 , wherein the first fluid exchange output of the fluid exchange module is fluidly coupled to an input of the second microfluidic channel of the particle concentration module.

3 . The microfluidic device of claim 1 , wherein the second fluid exchange output of the fluid exchange module is fluidly coupled to an input of the second microfluidic channel of the particle concentration module.

4 . The microfluidic device of claim 2 ,
comprising a first fluid sample input port and a second fluid sample input port, wherein the fluid exchange module is arranged to receive in the first microfluidic channel a first fluid sample from the first fluid sample input port and a second fluid sample from the second fluid sample input port.

5 . The microfluidic device of claim 3 ,
comprising a first fluid sample input port and a second fluid sample input port, wherein the fluid exchange module is arranged to receive in the first microfluidic channel a first fluid sample from the first fluid sample input port and a second fluid sample from the second fluid sample input port.

6 . The microfluidic device of claim 1 , wherein the first concentration module output of the particle concentration module is fluidly coupled to an input of the first microfluidic channel of the fluid exchange module.

7 . The microfluidic device of claim 6 , comprising a first fluid sample input port and a second fluid sample input port, wherein the particle concentration module is arranged to receive in the second microfluidic channel a first fluid sample from the first fluid sample input port, and wherein the fluid exchange module is arranged to receive in the first microfluidic channel a second fluid sample from the second fluid sample input port.

8 . A method of extracting and concentrating particles from bone marrow aspirate, the method comprising:
providing the bone marrow aspirate to a fluid exchange module of a microfluidic device; providing an aqueous solution to the fluid exchange module of the microfluidic device, the fluid exchange module comprising a corresponding first microfluidic channel and a first array of island structures in the first microfluidic channel, the first array of island structures being arranged in one or more rows that extend along a longitudinal direction of the first microfluidic channel, each island structure in a row being spaced apart from an adjacent island structure in the row to form an opening, wherein the bone marrow aspirate and the aqueous solution are provided to the fluid exchange module under conditions such that particle-free portions of the bone marrow aspirate are shifted through the opening between adjacent island structures within a row, and an inertial lift force causes the particles in the bone marrow aspirate to cross streamlines and transfer into the aqueous solution; passing, from the fluid exchange module, the aqueous solution containing the transferred particles, to a particle concentration module, the particle concentration module comprising a corresponding second microfluidic channel and a second array of island structures arranged in a row, each island structure within the second array of island structures being spaced apart from an adjacent island structure in the row to form an opening, wherein the aqueous solution containing the transferred particles is provided to the particle concentration module under conditions such that particle-free portions of the buffer solution are shifted through the opening between adjacent island structures within the second microfluidic channel, and such that the particles within the aqueous solution are focused to one or more streamlines within an inertial focusing section of the particle concentration module.

9 . The method of claim 8 , wherein the particles are nucleated cells.

10 . The method of claim 9 , wherein the nucleated cells are stem cells.

11 . A method of isolating and concentrating particles from a biological fluid sample, the method comprising:
obtaining the biological fluid sample; providing the biological fluid sample to a fluid exchange module of a microfluidic device; providing a second fluid sample to the fluid exchange module of the microfluidic device, the fluid exchange module comprising a corresponding first microfluidic channel and a first array of island structures in the first microfluidic channel, the first array of island structures being arranged in one or more rows that extend along a longitudinal direction of the first microfluidic channel, each island structure in a row being spaced apart from an adjacent island structure in the row to form an opening, wherein the biological fluid sample and the second fluid sample are provided to the fluid exchange module under conditions such that a first portion of the biological fluid sample comprising particles are shifted through the opening between adjacent island structures within a row, and an inertial lift force causes the particles in the biological fluid sample to cross streamlines and transfer into the second fluid sample; passing, from the fluid exchange module, the second fluid sample containing the transferred particles, to a particle concentration module, the particle concentration module comprising a corresponding second microfluidic channel and a second array of island structures arranged in a row, each island structure within the second array of island structures being spaced apart from an adjacent island structure in the row to form an opening, wherein the second fluid sample containing the transferred particles is provided to the particle concentration module under conditions such that particle-f

Assignees

• Massachusetts Gen Hospital

Inventors

• Kapur Ravi
• Smith Kyle C
• Toner Mehmet

Classifications

• G01N2015/1486

  Counting the particles · CPC title

• B01L2400/0409

  centrifugal forces · CPC title

• G01N15/1484 Primary

  microstructural devices · CPC title

• B01L2200/0668

  Trapping microscopic beads · CPC title

• B01L2300/0681

  Filter · CPC title