Extracorporeal clearance of organophosphates from blood on an acoustic separation device

Patent metadata

Field	Value
Publication number	US-9974898-B2
Application number	US-201615362068-A
Country	US
Kind code	B2
Filing date	Nov 28, 2016
Priority date	Jan 30, 2013
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

Systems, methods, and compositions for removing organophosphate toxins from blood are disclosed herein. The compositions include a lipid-based capture particle that displays BChE that binds to the toxin. The methods include acoustically separating toxins bound to lipid-based capture particles from blood factors of whole blood.

First claim

What is claimed:

1. A device for removing organophosphates from whole blood comprising:
a microfluidic separation channel having an upstream end and downstream end, the microfluidic separation channel comprising:
a first inlet configured to introduce flowing 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
an acoustic transducer positioned adjacent to the microfluidic separation channel for imposing a standing acoustic wave transverse to a flow of blood through a particle migration region of the microfluidic separation channel; and
a lipid-based capture particle injector containing lipid-based capture particles, the lipid-based capture particle injector configured to introduce lipid-based capture particles into the microfluidic separation channel, wherein the lipid-based capture particles comprise silicone oil and organophosphate affinity molecules linked to a first population of lipids.

2. The device of claim 1 , wherein the lipid-based capture particles further comprise a second population of lipids, wherein the second population of lipids form a lipid layer in which the first population of lipids is embedded.

3. The device of claim 1 , wherein the lipid-based capture particles are in the form of a liposome, vesicle, emulsion, lipid encapsulated droplet, or combinations thereof.

4. The device of claim 1 , wherein the organophosphate affinity molecules are BChE.

5. The device of claim 1 , wherein the organophosphate affinity molecules are linked to the first population of lipids with a PEG molecule.

6. The device of claim 1 , wherein the silicone oil is encapsulated within the lipid-based capture particles.

7. The device of claim 1 , wherein the lipid-based capture particle injector is configured to inject the lipid-based capture particles into the first inlet before a particle migration region of the microfluidic separation channel.

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

9. A method of cleansing blood of a subject comprising:
flowing whole blood into an inlet of a microfluidic separation channel wherein the whole blood comprises plasma and blood factors;
introducing lipid-based capture particles into the whole blood, wherein the lipid-based capture particles comprise silicone oil and organophosphate affinity molecules linked to a first population of lipids; and
applying a standing acoustic wave transverse to a direction of flow of the whole blood through the microfluidic separation channel such that the blood factors aggregate to about an axial center of the microfluidic separation channel and the lipid-based capture particles with bound organophosphates aggregate along at least one wall of the microfluidic separation channel.

10. The method of claim 9 , further comprising cycling off the standing acoustic wave such that a duty cycle of the standing acoustic wave is between about 75% and about 95%.

11. The method of claim 9 , further comprising collecting blood factors 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.

12. The method of claim 9 , further comprising collecting lipid-based capture particles through at least a second outlet positioned at a downstream end of the microfluidic separation channel adjacent to the at least one wall along which the lipid-based capture particles are aggregated.

13. The method of claim 9 , wherein the lipid-based capture particles further comprises a second population of lipids, wherein the second population of lipids form a lipid layer in which the first population of lipids is embedded.

14. The method of claim 9 , wherein the lipid-based capture particles have an opposite contrast factor than that of the blood factors.

15. The method of claim 9 , wherein the lipid-based capture particles are between about 10 μm and 20 μm in diameter.

16. A composition comprising organophosphate affinity molecules, a first population of lipids and silicone oil, wherein the organophosphate affinity molecules are linked to the first population of lipids, wherein the first population of lipids form a lipid-based capture particle, wherein the silicone oil is encapsulated within the lipid-based capture particle, and the organophosphate affinity molecules are displayed on the surface of the lipid-based capture particle.

17. The composition of claim 16 , further comprising a second population of lipids, wherein the second population of lipids form a lipid layer in which the first population of lipids is embedded.

18. The composition of claim 16 , wherein the organophosphate affinity molecules are BChE.

19. The composition of claim 16 , wherein the first population of lipids is selected from DSPE, DPPE, DMPE, or a combination thereof.

20. The composition of claim 17 , wherein the second population of lipids is selected from DOPC, DOPG, DOPE, or a combination thereof.

Assignees

• Charles Stark Draper Laboratory Inc

Inventors

• Spain Tammy
• Fiering Jason O
• Albers Leila

Classifications

• B01D21/283

  Settling tanks provided with vibrators · CPC title

• A61M1/362 Primary

  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

• A61M1/3623

  Means for actively controlling temperature of blood · CPC title

• A61M1/3693

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