Extracorporeal clearance of organophosphates from blood on an acoustic separation device
View Patent ↗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.
1. A device for removing organophosphates from whole blood comprising:
a microfluidic separation channel having an upstream end and downstream end, the separation channel comprising:
a first inlet configured to introduce flowing whole blood into a proximal end of the separation channel, wherein the whole blood includes or is suspected to include organophosphates;
a first outlet at the downstream end of the separation channel positioned substantially along the longitudinal axis of the separation channel;
a second outlet at the downstream end 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; and
a lipid-based capture particle injector containing lipid-based capture particles and configured to introduce lipid-based capture particles into the whole blood before the blood reaches the particle migration region of the separation channel, wherein the lipid-based capture particle comprises a first population of lipids and silicon oil; wherein the first population of lipids comprises organophosphate affinity molecules linked to the lipids in the first population of lipids, wherein the organophosphate affinity molecule is BChE.
2. The device of claim 1 , wherein the lipid-based capture particle further comprises a second population of lipids, wherein the second population of lipids form a lipid layer in which the first population 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 linked to the first population of lipids with a PEG molecule.
5. The device of claim 1 , wherein the silicone oil is encapsulated within the lipid-based particle.
6. The device of claim 1 , further comprising a reservoir in fluidic communication with the lipid-based capture particle injector.
7. The device of claim 1 , wherein the lipid-based particle is a liposome.
8. The device of claim 1 , wherein the separation channel comprises walls having a thickness at a particle aggregation point that is greater than a multiple of one quarter of the wavelength of an acoustic wave acting on the walls of the 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, and includes or is suspected to include organophosphates;
introducing lipid-based capture particles into the whole blood which bind to the organophosphates, wherein the lipid-based capture particle comprises a first population of lipids and silicone oil; wherein the first population of lipids comprises an organophosphate affinity molecule linked to the lipids of the first population of lipids, wherein said organophosphate affinity molecule is BChE; and
applying a standing acoustic wave transverse to a direction of flow of the whole blood through the separation channel such that the blood factors aggregate to about the axial center of the separation channel and the lipid-based capture particles with bound organophosphates aggregate along at least one wall of the separation channel.
10. The method of claim 9 , 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%.
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 separation channel at about the axial center of the separation channel.
12. The method of claim 9 , further comprising collecting lipid-based capture particles through at least a second outlet positioned at the downstream end of the 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 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. The method of claim 9 , further comprising:
reintroducing the blood factors back into the subject after flowing the whole blood through the microfluidic separation channel.
17. A composition comprising organophosphate affinity molecules, a first population of lipids and silicon oil, wherein the organophosphates 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, wherein said organophosphate affinity molecule is BChE.
18. 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 is embedded.
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.