System and method for blood separation by microfluidic acoustic focusing

Patent metadata

Field	Value
Publication number	US-2023218813-A1
Application number	US-202318121192-A
Country	US
Kind code	A1
Filing date	Mar 14, 2023
Priority date	Mar 8, 2013
Publication date	Jul 13, 2023
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 - 13 . (canceled)

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 defined in a thermoplastic; selecting a wavelength of a standing acoustic wave such that a predetermined width of the microfluidic separation channel is between 30% an 45% of the wavelength of the standing acoustic wave; and applying the standing acoustic wave transverse to a direction of flow of the whole blood through the microfluidic separation channel such that the plurality of formed elements aggregate toward the axial center of the microfluidic separation channel.

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

16 . The method of claim 14 , wherein a thickness of a wall of the microfluidic separation channel is between about 35% and about 45% of the wavelength of the standing acoustic wave applied to the microfluidic separation channel.

17 . The method of claim 14 , further comprising introducing a plurality of lipid-based capture particles into the whole blood such that the plurality of lipid-based capture particles bind to the plurality of undesirable particles.

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

19 . The method of claim 17 , further comprising collecting the plurality of lipid-based capture particles through at least a second outlet positioned at a downstream end of the microfluidic separation channel adjacent to at least one wall along which the plurality of lipid-based capture particles are aggregated.

20 . The method of claim 17 , wherein the plurality of lipid-based capture particles comprise an affinity molecule anchored to a lipid bilayer encapsulating a fluid.

21 . The method of claim 17 , wherein introducing the plurality of lipid-based capture particles into the whole blood comprises introducing the plurality of lipid-based capture particles using a capture particle injector before the whole blood reaches a particle migration region of the microfluidic separation channel.

22 . The method of claim 17 , further comprising forming the plurality of lipid-based capture particles from a mixture of materials comprising an affinity molecule, a lipid, and a fluid with a density less than about 1 g/cm 3 .

23 . The method of claim 22 , wherein forming the plurality of lipid-based capture particles comprises injecting the mixture of materials comprising the affinity molecule, the lipid, and the fluid through a nozzle such that the lipid forms a liposome surrounding a portion of the fluid.

24 . 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 defined in a thermoplastic, the microfluidic separation channel having and an upstream end and downstream end, the microfluidic separation channel comprising:
a first inlet configured to introduce the whole blood into a proximal end of the microfluidic separation channel;
a first outlet at the downstream end of the microfluidic separation channel positioned substantially along a longitudinal axis of the microfluidic separation channel;
a second outlet at the downstream end positioned adjacent a first wall of the microfluidic separation channel; and
selecting a wavelength of a standing acoustic wave such that a predetermined width of the microfluidic separation channel is between 25% an 35% of an acoustic wavelength in the whole blood at a predetermined frequency; and applying, via an acoustic transducer coupled to the microfluidic separation channel that operates at the predetermined frequency, the standing acoustic wave across a particle migration region and transverse to a direction of flow of the whole blood through the microfluidic separation channel, such that the plurality of formed elements aggregate toward the axial center of the microfluidic separation channel.

25 . The method of claim 24 , wherein the predetermined width of the microfluidic separation channel is between about 30% and about 35% of the wavelength of the standing acoustic wave applied to the microfluidic separation channel.

26 . The method of claim 24 , wherein a thickness of a wall of the microfluidic separation channel is between about 35% and about 45% of the wavelength of the standing acoustic wave applied to the microfluidic separation channel.

27 . The method of claim 24 , further comprising introducing a plurality of lipid-based capture particles into the whole blood such that the plurality of lipid-based capture particles bind to the plurality of undesirable particles.

28 . The method of claim 24 , further comprising collecting the plurality of formed elements of the whole blood at the first outlet positioned at the downstream end of the microfluidic separation channel at about the axial center of the microfluidic separation channel.

29 . The method of claim 27 , further comprising collecting the plurality of lipid-based capture particles through at least the second outlet positioned at the downstream end of the microfluidic separation channel adjacent to at least one wall along which the plurality of lipid-based capture particles are aggregated.

30 . The method of claim 27 , wherein the plurality of lipid-based capture particles comprise an affinity molecule anchored to a lipid bilayer encapsulating a fluid.

31 . The method of claim 27 , wherein introducing the plurality of lipid-based capture particles into the whole blood comprises introducing the plurality of lipid-based capture particles using a capture particle injector before the whole blood reaches the particle migration region of the microfluidic separation channel.

32 . The method of claim 27 , further comprising forming the plurality of lipid-based capture particles from a mixture of materials comprising an affinity molecule, a lipid, and a fluid with a density less than about 1 g/cm 3 .

33 . The method of claim 32 , wherein forming the plurality of lipid-based capture particles comprises injecting the mixture of materials comprising the affinity molecule, the lipid, and the fluid through a nozzle such that the lipid forms a liposome surrounding a portion of the fluid.

Assignees

• Charles Stark Draper Laboratory Inc

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

• B01D2221/10

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

• A61M1/3678

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

• B01D21/283

  Settling tanks provided with vibrators · CPC title