System and method for inertial focusing microfiltration for intra-operative blood salvage autotransfusion

Patent metadata

Field	Value
Publication number	US-10806845-B2
Application number	US-201515511499-A
Country	US
Kind code	B2
Filing date	Sep 17, 2015
Priority date	Sep 17, 2014
Publication date	Oct 20, 2020
Grant date	Oct 20, 2020

Abstract

A system for intra-operative blood salvage autotransfusion is provided. The system comprises at least one inlet configured to receive whole blood of a patient; at least one curvilinear microchannel in fluid flow connection with the at least one inlet, the at least one curvilinear microchannel being adapted to isolate circulating tumor cells in the whole blood, based on cell size, along at least one portion of a cross-section of the at least one curvilinear microchannel; and at least two outlets in fluid flow connection with the at least one curvilinear microchannel, at least one outlet of the at least two outlets being configured to flow the circulating tumor cells isolated from the whole blood, and at least one other outlet of the at least two outlets being configured to flow at least a portion of a remainder of the whole blood, cleansed of the isolated circulating tumor cells, for return to the patient.

First claim

What is claimed is:

1. A system for intra-operative blood salvage autotransfusion, the system comprising:
at least one inlet configured to receive whole blood of a patient during a cancer surgery of the patient;
a plurality of curvilinear microchannels in fluid flow connection with the at least one inlet, the plurality of curvilinear microchannels being adapted to isolate circulating tumor cells in the whole blood, based on cell size, along at least one portion of a cross-section of such curvilinear microchannels;
at least two outlets in fluid flow connection with the plurality of curvilinear microchannels, at least one outlet of the at least two outlets being configured to flow the circulating tumor cells isolated from the whole blood, and at least one other outlet of the at least two outlets being configured to flow at least a portion of a remainder of the whole blood, cleansed of the isolated circulating tumor cells, to the patient as an autotransfusion;
the plurality of curvilinear microchannels flowing the whole blood at a flow rate, and the cross-section comprising a width and a height, such that the curvilinear microchannels are adapted to focus the circulating tumor cells near one wall of the curvilinear microchannels while also dispersing another component of the whole blood across a width of the curvilinear microchannels;
the plurality of curvilinear microchannels being multiplexed with each other to circulate the whole blood to be processed in a plurality of curvilinear microchannel cycles such that: (i) greater than 92% of the circulating tumor cells are directed to the at least one outlet that is configured to flow the circulating tumor cells isolated from the whole blood; and (ii) greater than 90% of each of: a red blood cell component of the whole blood, a white blood cell component of the whole blood, and a platelets component of the whole blood, are directed to the at least one other outlet that is configured to flow the at least a portion of the remainder of the whole blood to the patient as an autotransfusion.

2. The system of claim 1 , wherein the plurality of curvilinear microchannels comprise a plurality of spiral channels.

3. The system of claim 1 , wherein the system comprises a plurality of channel layers attached to each other, each channel layer of the plurality of channel layers comprising at least some curvilinear microchannels of the plurality of curvilinear microchannels;
the system further comprising a guide layer attached to the plurality of channel layers, the guide layer comprising a common inlet and at least two common outlets for the plurality of curvilinear microchannels.

4. The system of claim 1 , configured to receive a continuous flow of whole blood at the at least one inlet,
and to provide a continuous flow of isolated circulating tumor cells to the at least one outlet of the at least two outlets,
and to provide a continuous flow of the at least a portion of the remainder of the whole blood for return to the patient.

5. The system of claim 1 , wherein the plurality of curvilinear microchannels is adapted to isolate the circulating tumor cells solely due to hydrodynamic forces in the plurality of curvilinear microchannels, without use of a membrane in the microfluidic system.

6. The system of claim 1 , wherein the curvilinear microchannels of the plurality of curvilinear microchannels have a length, and the cross-section has a height and a width defining an aspect ratio, such that the curvilinear microchannels are adapted, by virtue of the length and the cross-section, to isolate the circulating tumor cells in the whole blood along the portions of the cross-section of such channels based on the cell size.

7. The system of claim 1 , wherein the cross-section of the curvilinear microchannels of the plurality of curvilinear microchannels is a trapezoidal cross section defined by a radially inner side, a radially outer side, a bottom side, and a top side, the trapezoidal cross section having a) the radially inner side and the radially outer side unequal in height, or b) the radially inner side equal in height to the radially outer side, and wherein the top side has at least two continuous straight sections, each unequal in width to the bottom side.

8. The system of claim 1 , wherein the cross-section of the curvilinear microchannels of the plurality of curvilinear microchannels is a rectangular cross-section.

9. The system of claim 1 , wherein the curvilinear microchannels of the plurality of curvilinear microchannels are adapted to filter the whole blood by isolating the circulating tumor cells in the whole blood near one side of the curvilinear microchannels, and to collect the at least a portion of the remainder of the whole blood on another side of the curvilinear microchannels.

10. The system of claim 1 , wherein the at least a portion of the remainder of the whole blood comprises white blood cells, red blood cells and platelets at substantially the same concentrations as in the whole blood received at the at least one inlet.

11. The system of claim 1 , wherein the at least a portion of the remainder of the whole blood is substantially not depleted of white blood cells.

12. The system of claim 1 , wherein at least about 95% of any circulating tumor cells in the whole blood received at the at least one inlet are isolated as the isolated circulating tumor cells.

13. The system of claim 1 , wherein the plurality of curvilinear microchannels are multiplexed with each other to flow at least about 200 milliliters per minute of the whole blood from the at least one other outlet to the patient as the autotransfusion.

14. A method for intra-operative blood salvage autotransfusion, the method comprising:
receiving whole blood of a patient during a cancer surgery of the patient and flowing the whole blood of the patient through at least one inlet of a system for intra-operative blood salvage autotransfusion;
flowing the whole blood from the at least one inlet through a plurality of curvilinear microchannels of the system in fluid flow connection with the at least one inlet, thereby isolating circulating tumor cells in the whole blood, based on cell size, along at least one portion of a cross-section of such curvilinear microchannels;
flowing the isolated circulating tumor cells through at least one outlet of at least two outlets of the system that are in fluid flow connection with the plurality of curvilinear microchannels, and flowing at least a portion of a remainder of the whole blood, cleansed of the isolated circulating tumor cells, through at least one other outlet of the at least two outlets of the system, to the patient as an autotransfusion;
the flowing the whole blood through the plurality of curvilinear microchannels comprising flowing the whole blood at a flow rate, and the cross-section comprising a width and a height, such that the circulating tumor cells are focused near one wall of the curvilinear microchannels while another component of the whole blood is dispersed across a width of the curvilinear microchannels;
the flowing of the whole blood comprising circulating the whole blood in a plurality of curvilinear microchannel cycles, such that: (i) greater than 92% of the circulating tumor cells are directed to the at least one outlet that flows the circulating tumor cells isolated from the whole blood; and (ii) greater than 90% of each of: a red blood cell component of the whole blood, a white blood cell component of the whole blood, and a platelets component of the whole blood, are directed to the at least one other outlet to the patient as an autotransfusion.

15. The met

Assignees

• Massachusetts Inst Technology
• Nat Univ Singapore

Inventors

• Ebrahimi Warkiani Majid
• Guan Guofeng
• Tay Kah Ping Andy
• Wu Lidan
• Han Jongyoon
• Lim Chwee Teck

Classifications

• A61M2202/20

  Pathogenic agents · CPC title

• A61M2205/0244

  Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology · CPC title

• A61M1/0281

  Apparatus for treatment of blood or blood constituents prior to transfusion, e.g. washing, filtering or thawing · CPC title

• A61M2206/10

  Flow characteristics · CPC title

• A61M2202/09

  Body tissue · CPC title