System and method for blood separation by microfluidic acoustic focusing

Patent metadata

Field	Value
Publication number	US-9731062-B2
Application number	US-201213598401-A
Country	US
Kind code	B2
Filing date	Aug 29, 2012
Priority date	Aug 29, 2011
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

Systems and methods for cleansing blood are disclosed herein. The methods include acoustically separating undesirable particles bound to capture particles from formed elements of whole blood. After introducing the capture particles to whole blood containing undesirable particles, the whole blood and capture particles are flowed through a microfluidic separation channel. At least one bulk acoustic transducer is attached to the microfluidic separation channel. A standing acoustic wave, imparted on the channel and its contents by the bulk acoustic transducer, drives the formed elements and undesirable particles bound to capture particles to specific aggregation axes. After aggregating the particles, the formed elements exit the separation channel through a first outlet and are returned to the patient. The undesirable particles, bound to the capture particles, exit through a second outlet and can be discarded to saved for later study.

First claim

What is claimed is:

1. A blood cleansing device configured for microfluidic separation of undesirable particles from formed elements of whole blood, the blood cleansing device comprising:
at least one separation channel configured to provide (a) a first portion where a first standing acoustic wave drives the formed elements of the whole blood and the captures particles along a first longitudinal axis parallel and against to a wall of the at least one separation channel and (b) a second portion where a second standing acoustic wave drives the formed elements of the whole blood toward a second longitudinal axis in an interior region of the second portion and parallel to the wall of the at least one separation channel, the at least one separation channel further comprising:
a first inlet configured to introduce the whole blood and the plurality of capture particles into the first portion of the at least one separation channel, the whole blood including plasma, the plurality of formed elements having a first positive contrast factor and the plurality of undesirable particles having a second positive contrast factor less than the first positive contrast factor;
a first outlet positioned within the separation channel downstream from the first inlet;
a second outlet for the removal of the plurality of capture particles bound to at least a portion of the plurality of undesirable particles, the second outlet positioned against the wall of the at least one separation channel and downstream of the first inlet;
a second inlet positioned within the separation channel downstream of the first outlet and upstream of the second outlet; and
a third outlet for the removal of the plurality of formed elements, the third outlet positioned parallel with the second longitudinal axis in the interior region of the second portion and parallel to the wall of the at least one separation channel in the second portion of the at least one separation channel and positioned away from the wall of the at least one separation channel a first distance proportional to a distance from the second standing acoustic wave, a flow rate of the whole blood, and the first negative contrast factor, wherein the at least one separation channel is configured to separate the plurality of undesirable particles from the formed elements by:
(i) aggregating the plurality of undesirable particles bound to the plurality of capture particles at a first pressure node in the first portion of the at least one separation channel and aligned with the first longitudinal axis parallel and against to a wall of the at least one separation channel;
(ii) driving the formed elements of the whole blood toward a second pressure node in the second portion of the at least one separation channel and aligned with the second longitudinal axis in the interior region of the second portion and parallel to the wall of the at least one separation channel, wherein the formed elements are driven at least the first distance away from the wall and into the third outlet; and
(iii) driving the plurality of capture particles bound to the plurality of undesirable particles toward the second pressure node in the second portion of the at least one separation channel aligned with the second longitudinal axis a second distance less than the first distance.

2. The blood cleansing device of claim 1 , comprising at least a second separation channel and a third separation channel, wherein:
a first outlet of the second separation channel is configured to carry fluid from the second separation channel to the second inlet of the separation channel, and
a second inlet of the third separation channel is configured to receive fluid from the first outlet of the separation channel.

3. The blood cleansing device of claim 1 , comprising a microfluidic injector for introducing, into the separation channel, the plurality capture particles configured to bind to the undesirable particles.

4. The blood cleansing device of claim 3 , wherein the plurality of capture particles are lipid-based and the microfluidic injector comprises one of a microfluidic nozzle and a porous membrane coupled to a lipid reservoir.

5. The device of claim 1 , wherein the separation channel is formed in a substrate comprising one of polystyrene, glass, polyimide, acrylic, polysulfone, and silicon.

6. The blood cleansing device of claim 1 , comprising an acoustic transducer positioned adjacent to the separation channel and configured to impose the first standing wave transverse to the length of the first portion of the at least one separation channel, wherein the first standing wave is configured to focus the formed elements and the plurality of the undesirable particles bound to the plurality of capture particles towards an interior region of the first portion of the at least one separation channel.

7. The blood cleansing device of claim 6 , comprising a second acoustic transducer positioned adjacent to the second portion of the at least one separation channel and configured to impose the second standing wave transverse to the length of the second portion of the at least one separation channel, wherein the second standing wave is selected such that the formed elements are be driven toward the second pressure node at a rate that is faster than a rate at which the second standing wave drives the undesirable particles bound to the capture agents toward the second pressure node.

8. The blood cleansing device of claim 6 , wherein the second outlet is positioned sufficiently downstream within the second portion of the at least one separation channel that in operation, a greater percentage of the undesirable particles that are bound to the plurality of capture particles flows out of the second outlet than out of the third outlet and a greater percentage of the formed elements flows out of the third outlet than out of the second outlet.

9. The device of claim 1 , wherein the first portion of the separation channel comprises an aggregation point, and the first portion of the at least one separation channel is configured such that a width of the first portion of the at least one separation channel at the aggregation point is half the wavelength of an acoustic wave acting on the whole blood.

10. The device of claim 1 , wherein the at least one separation channel comprises walls having a thickness at a particle aggregation point that is a multiple of one quarter of the wavelength of an acoustic wave acting on the walls of the at least one separation channel.

11. The device of claim 1 , wherein the height of the at least one separation channel at a particle aggregation point is less than one quarter of the wavelength of an acoustic wave acting on the particle aggregation point.

12. A method of cleansing blood comprising
flowing whole blood, containing a plurality of undesirable particles, formed elements having a second contrast factor, and plasma, through a microfluidic separation channel;
introducing capture particles having a first contrast factor less than the second contrast factor, from a reservoir, into whole blood such that the capture particles can bind to at least a plurality of the undesirable particles;
aggregating, in a first portion of the separation channel, with a first standing acoustic wave, the formed elements of the whole blood and the captures particles to a first aggregation axis a first distance from a first wall of the separation channel in a second portion of the separation channel;
directing, downstream of the first portion of the separation channel, the captures particles and the formed elements alongside the first wall of the separation channel that is aligned with the first aggregation axis of the sep

Assignees

• Fiering Jason O
• Sundaram Shivshankar
• Charles Stark Draper Laboratory Inc

Inventors

• Fiering Jason O
• Sundaram Shivshankar

Classifications

• B01D2221/10

  Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues · CPC title

• G01N33/491

  by separating the blood components (G01N15/05 takes precedence) · CPC title

• A61M1/3693 Primary

  using separation based on different densities of components, e.g. centrifuging · CPC title

• A61M1/362

  changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity · CPC title

• B01D21/283

  Settling tanks provided with vibrators · CPC title