System and method for blood separation by microfluidic acoustic focusing

Patent metadata

Field	Value
Publication number	US-2016008532-A1
Application number	US-201414772216-A
Country	US
Kind code	A1
Filing date	Mar 10, 2014
Priority date	Mar 8, 2013
Publication date	Jan 14, 2016
Grant date	—

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

1 . A blood cleansing device comprising:
a thermoplastic microfluidic separation channel having an upstream portion and downstream portion, the separation channel comprising: a first inlet configured to introduce flowing whole blood into a proximal portion of the separation channel, the whole blood including plasma, a plurality of formed elements and a plurality of undesirable particles; a first outlet at the downstream portion of the separation channel positioned substantially along the longitudinal axis of the separation channel; a second outlet at the downstream portion positioned adjacent a first wall of the separation channel; and an acoustic transducer positioned adjacent to the separation channel for imposing a standing acoustic wave transverse to the flow of blood through a particle migration region of the separation channel, wherein a width of the separation channel is between about 30% and 45% of a wavelength of the standing acoustic wave.

2 . The blood cleansing device of claim 1 , wherein the width of the separation channel is between about 30% and about 35% of the wavelength of the standing wave applied to the separation channel.

3 . The blood cleansing device of claim 1 , wherein a thickness of the wall is between about 25% and about 45% of the wavelength of the standing wave applied to the separation channel.

4 . (canceled)

5 . The blood cleansing device of claim 1 , further comprising a capture particle injector configured to introduce a plurality of lipid-based capture particles into the whole blood before the blood reaches the particle migration region of the separation channel.

6 - 9 . (canceled)

10 . The blood cleansing device of claim 5 , wherein the lipid-based capture particles have significantly different acoustophoretic mobility than that of formed elements of blood.

11 - 12 . (canceled)

13 . The blood cleansing device of claim 1 , further comprising a third outlet, wherein the second and third outlets merge at a fourth outlet.

14 . A method of cleansing blood comprising:
flowing whole blood, including plasma, a plurality of formed elements, and a plurality of undesirable particles, into an inlet of a microfluidic separation channel; introducing a plurality of lipid-based capture particles into the whole blood such that the lipid-based capture particles bind to a plurality of the undesirable particles; and applying a standing acoustic wave transverse to a direction of flow of the whole blood through the separation channel such that the formed elements aggregate to about the axial center of the separation channel and the capture particles aggregate along at least one wall of the separation channel, wherein a width of the separation channel is between about 30% and 45% of a wavelength of the standing acoustic wave.

15 . The method of claim 14 , wherein the width of the separation channel is between about 30% and about 35% of the wavelength of the standing wave applied to the separation channel.

16 . The method of claim 14 , wherein a thickness of the wall is between about 25% and about 45% of the wavelength of the standing wave applied to the separation channel.

17 . (canceled)

18 . The method of claim 14 , further comprising collecting formed elements of the whole blood at a first outlet positioned at a downstream portion of the separation channel at about the axial center of the separation channel.

19 . The method of claim 14 , further comprising collecting capture particles through at least a second outlet positioned at the downstream portion of the separation channel adjacent to the at least one wall along which the capture particles are aggregated.

20 . The method of claim 14 , wherein the capture particles comprise an affinity molecule anchored to a lipid bilayer encapsulating a fluid.

21 . The method of claim 14 , wherein the fluid has a density less than about 1 g/cm 3 .

22 . The method of claim 14 , wherein affinity molecule, lipid, and fluid are mixed in the reservoir prior to their injection into the separation channel.

23 . (canceled)

24 . The method of claim 14 , wherein the capture particles have an opposite contrast factor than that of formed elements of blood.

25 . The method of claim 14 , wherein the capture particles are between about 10 μm and 20 μm in diameter.

26 . The method of claim 14 , further comprising:
extracting whole blood from a patient prior to flowing the whole blood through the separation channel, the extracted whole blood having a first concentration of undesirable particles; and reintroducing whole blood with fewer undesirable particles back into the patient after flowing whole blood through the plurality of microchannels.

27 . The method of claim 14 , further comprising cycling off the standing acoustic wave such that the duty cycle of the standing acoustic wave is between about 75% and about 95%.

28 - 35 . (canceled)

36 . The blood cleansing device of claim 1 , wherein the standing wave is configured to focus the plurality of formed elements and a plurality of the undesirable particles bound to a plurality of capture agents towards an interior region of the upstream portion of the channel.

37 . The blood cleansing device of claim 36 , wherein the acoustic transducer is configured to operate at a duty cycle of about 75%-95%.

38 - 68 . (canceled)

Assignees

• Draper Lab Charles S

Inventors

• Fiering Jason O
• Sundaram Shivshanker
• Meuller Andrew

Classifications

• A61M1/3693 Primary

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

• A61M1/3678

  Separation of cells using wave pressure; Manipulation of individual corpuscles · CPC title

• B01D21/283

  Settling tanks provided with vibrators · 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

• B01D2221/10

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