Acoustic separation of particles for bioprocessing

Patent metadata

Field	Value
Publication number	US-12332235-B2
Application number	US-202318528061-A
Country	US
Kind code	B2
Filing date	Dec 4, 2023
Priority date	Apr 28, 2017
Publication date	Jun 17, 2025
Grant date	Jun 17, 2025

Abstract

A method for separating particles in a biofluid includes pretreating the biofluid by introducing an additive, flowing the pretreated biofluid through a microfluidic separation channel, and applying acoustic energy to the microfluidic separation channel. A system for microfluidic separation, capable of separating target particles from non-target particles in a biofluid includes at least one microfluidic separation channel, a source of biofluid, a source of additive, and at least one acoustic transducer coupled to the microfluidic separation channel. A kit for microfluidic particle separation includes a microfluidic separation channel connected to an acoustic transducer, a source of an additive, and instructions for use.

First claim

What is claimed is:

1. A system for microfluidic particle separation configured to separate target particles from non-target particles in a biofluid, the system comprising:
at least one microfluidic separation channel comprising at least one inlet, a first outlet, and a second outlet, a first collection channel in fluid communication with the first outlet and a second collection channel in fluid communication with the second outlet;
a source of the biofluid in fluid communication with the at least one inlet of the at least one microfluidic separation channel;
a source of an additive in fluid communication with the source of the biofluid, configured to introduce at least one additive into the biofluid, the additive capable of altering one or more physical properties of at least one of the target particles, non-target particles, or biofluid,
at least one acoustic transducer coupled to a wall of the at least one microfluidic separation channel;
a recycle line extending from the second collection channel in fluid communication with the source of the biofluid, configured to recycle target particle depleted fluid from the second outlet to the source of the biofluid;
at least one sensor configured to measure at least one of HCT % of the biofluid and concentration of target particles or non-target particles; and
a control module in electrical communication with the at least one sensor and the source of the additive, configured to introduce a predetermined volume of the additive into the biofluid in response to a measurement of at least one of HCT % of the biofluid and concentration of the target particles or the non-target particles in the biofluid.

2. The system of claim 1 , wherein the at least one acoustic transducer is positioned to apply a standing acoustic wave transverse to the microfluidic separation channel.

3. The system of claim 1 , comprising at least two microfluidic separation channels connected in parallel and a manifold configured to distribute the biofluid to the at least two microfluidic separation channels.

4. The system of claim 1 , further comprising at least one output sensor configured to measure at least one parameter of an output suspension.

5. The system of claim 4 , wherein the at least one output sensor is configured to measure at least one of hematocrit (HCT %) of the output suspension and concentration of the target particles or the non-target particles in the output suspension.

6. The system of claim 5 , wherein the control module is configured to regulate at least one of power, voltage, and frequency delivered to the acoustic transducer in response to a measurement of the at least one parameter in the output suspension.

7. The system of claim 6 , wherein the additive is further configured to regulate the HCT % of the output suspensions, and the control module is configured to regulate the HCT % of the output suspension to less than about 1% by regulating a volume of the additive introduced to the microfluidic separation channel.

8. The system of claim 1 , wherein the predetermined volume of the additive is determined to regulate the HCT % of the biofluid to less than about 10%.

9. The system of claim 1 , further comprising a source of a second fluid in fluid communication with the at least one inlet of the at least one microfluidic separation channel, configured to introduce the second fluid into the biofluid, such that the biofluid and the second fluid flow in substantially parallel, substantially laminar flow.

10. The system of claim 1 , wherein the first or second collection channel is in fluid communication with a collection vessel.

11. The system of claim 1 , further comprising an intraluminal line in fluid communication with a donor subject and the source of the biofluid, configured to extract biofluid from the donor subject and deliver the biofluid to the source of the biofluid.

12. The system of claim 1 , further comprising an intraluminal line in fluid communication with one of the first and the second outlet of the separation channel and a recipient subject, configured to deliver output suspension to the recipient subject.

13. The system of claim 1 , wherein the microfluidic separation channel is formed from a thermoplastic material.

14. A system for microfluidic particle separation configured to separate target particles from non-target particles in a biofluid, the system comprising:
at least one microfluidic separation channel comprising at least one inlet, a first outlet, and a second outlet, a first collection channel in fluid communication with the first outlet and a second collection channel in fluid communication with the second outlet;
a source of the biofluid in fluid communication with the at least one inlet of the at least one microfluidic separation channel;
a source of an additive in fluid communication with the source of the biofluid, configured to introduce at least one additive into the biofluid, the additive capable of altering one or more physical properties of at least one of the target particles, non-target particles, or biofluid;
at least one acoustic transducer coupled to a wall of the at least one microfluidic separation channel to apply a standing acoustic wave transverse to the at least one microfluidic separation channel to drive the particles to a node or anti-node within the separation channel;
at least one output sensor is configured to measure at least one of hematocrit (HCT %) of the output suspension and concentration of the target particles or the non-target particles in the output suspension; and
at least one control module in electric communication with the at least one output sensor and the acoustic transducer, wherein the additive is further configured to regulate the HCT % of the output suspensions, and the control module is configured to regulate the HCT % of the output suspension to less than about 1% by regulating a volume of the additive introduced to the microfluidic separation channel.

15. The system of claim 14 , wherein the acoustic transducer includes a piezoelectric vibrating element configured to emit acoustic energy to drive denser and larger particles to a center of the separation channel.

16. The system of claim 14 , wherein the acoustic transducer includes a piezoelectric vibrating element configured to provide standing acoustic waves having a wavelength twice as long as a width of the microfluidic separation channel.

17. The system of claim 14 , further comprising a heat sink configured to dissipate heat generated by the acoustic transducer.

18. The system of claim 17 , wherein the heat sink includes a thermoelectric cooler.

Assignees

• Charles Stark Draper Laboratory Inc

Inventors

• Fiering Jason O
• Kotz Kenneth T

Classifications

• G01N2015/1028

  Sorting particles · CPC title

• G01N15/01

  specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) · CPC title

• B01L2200/0652

  Sorting or classification of particles or molecules · CPC title

• B03B1/04

  by additives · CPC title

• G01N2015/0681

  Purposely modifying particles, e.g. humidifying for growing · CPC title