Acoustic separation of particles for bioprocessing

Patent metadata

Field	Value
Publication number	US-10914723-B2
Application number	US-201815965368-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	Apr 28, 2017
Publication date	Feb 9, 2021
Grant date	Feb 9, 2021

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 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 at least one of:
size of the target particles,
size of the non-target particles,
compressibility of the biofluid,
compressibility of the target particles,
compressibility of the non-target particles,
aggregation potential of the target particles, and
aggregation potential of the non-target particles;

the additive being further capable of altering at least one of:
density of the biofluid,
density of the target particles, and
density of the non-target particles;

at least one acoustic transducer coupled to a wall of the at least one microfluidic separation channel;
at least one first sensor configured to measure at least one of density of the biofluid and concentration of target particles or non-target particles; and
a control module in electrical communication with the at least one first 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 the density of the biofluid and the concentration 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 , further 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 3 , further comprising at least one second sensor configured to measure an input biofluid load on the system.

5. The system of claim 4 , wherein the manifold is in electrical communication with the at least one second sensor, configured to distribute the biofluid to the at least two microfluidic separation channels in response to a measurement of the input biofluid load on the system.

6. The system of claim 1 , wherein the predetermined volume is determined to regulate the density of the biofluid to substantially match a density of the target particles.

7. The system of claim 6 , wherein the predetermined volume is determined to regulate the density of the biofluid to a density of between about 1.00 g/mL and about 1.15 g/mL.

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

9. The system of claim 8 , wherein the at least one third 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.

10. The system of claim 8 , wherein the control module is in electrical communication with the at least one third sensor and the acoustic transducer, 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.

11. The system of claim 9 , wherein the control module is in electrical communication with the at least one third sensor and the acoustic transducer or source of the additive, configured to regulate the HCT % of the output suspension to less than about 1% in response to a measurement of the at least one parameter in the output suspension.

12. The system of claim 1 , further comprising at least one fourth sensor configured to measure at least one of HCT % of the biofluid and concentration of target particles or non-target particles.

13. The system of claim 12 , wherein the control module is in electrical communication with the at least one fourth 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 the HCT % of the biofluid and the concentration the target particles or the non-target particles in the biofluid.

14. The system of claim 13 , wherein the predetermined volume of the additive is determined to regulate the HCT % of the biofluid to less than about 10%.

15. 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.

16. The system of claim 1 , further comprising a first collection channel in fluid communication with the first outlet of the microfluidic separation channel and a second collection channel in fluid communication with the second outlet of the microfluidic separation channel.

17. The system of claim 16 , wherein the second collection channel comprises a recycle line 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.

18. The system of claim 16 , wherein the first or second collection channel is in fluid communication with a collection vessel.

19. The system of claim 1 , connectable to 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.

20. The system of claim 1 , connectable to 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.

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

22. The system of claim 1 , further comprising a first collection channel in fluid communication with the first outlet of the microfluidic separation channel and a second collection channel in fluid communication with the second outlet of the microfluidic separation channel.

23. The system of claim 22 , wherein the second collection channel comprises a recycle line 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.

24. The system of claim 22 , wherein the first or second collection channel is in fluid communication with a collection vessel.

25. 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 source of 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

Assignees

• Charles Stark Draper Laboratory Inc

Inventors

• Fiering Jason O
• Kotz Kenneth T

Classifications

• A61M1/3616

  Batch-type treatment · CPC title

• B01L2400/0436

  acoustic forces, e.g. surface acoustic waves [SAW] · CPC title

• A61M1/3678

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

• G01N2015/0687

  in solutions, e.g. non volatile residue · CPC title

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title