Acoustic methods for separation of cells and pathogens

Patent metadata

Field	Value
Publication number	US-2016363579-A1
Application number	US-201615180015-A
Country	US
Kind code	A1
Filing date	Jun 11, 2016
Priority date	Jun 11, 2015
Publication date	Dec 15, 2016
Grant date	—

Abstract

Devices and methods for inspecting, detecting, isolating, monitoring, characterizing, or separating pathogens in blood containing blood cells are disclosed. The devices include a flow chamber having a solvent inlet, at least one host-fluid inlet, a particulate outlet, at least one residual outlet, and a reflector. The methods include trapping the pathogens in the acoustic standing wave, introducing a solvent into the flow chamber, and removing the pathogens from the device. Devices and methods for inspecting, detecting, isolating, monitoring, characterizing, or separating specialized circulating cells in blood containing blood cells are also disclosed. The devices include a flow chamber having at least one inlet and at least one outlet, and a microscope objective and a cover glass. The methods include driving the transducer to create an acoustic standing wave in the flow chamber and microbubbles in the blood.

First claim

1 . A method for inspecting, detecting, isolating, monitoring, characterizing, or separating target cells in a host fluid also containing non-target cells, the method comprising:
flowing the host fluid containing the target cells and the non-target cells through an acoustophoretic device, the acoustophoretic device comprising:
a flow chamber having a solvent inlet and at least one host-fluid inlet at a first end of the flow chamber, and a particulate outlet and at least one residual outlet at a second end of the flow chamber opposite the first end thereof, wherein the solvent inlet and the particulate outlet are aligned with a longitudinal axis of the flow chamber and the at least one host-fluid inlet and the at least one residual outlet are spaced apart from the longitudinal axis;
at least one ultrasonic transducer located on a wall of the flow chamber, the at least one ultrasonic transducer including a piezoelectric material driven by a voltage signal to create an acoustic standing wave in the flow chamber; and
a reflector located on a wall on the opposite side of the flow chamber from the at least one ultrasonic transducer;
sending a voltage signal to drive the at least one ultrasonic transducer to create the acoustic standing wave in the flow chamber to drive the target cells toward the longitudinal axis where the target cells become trapped in the acoustic standing wave; introducing a solvent into the flow chamber through the solvent inlet; and removing the target cells from the device through the particulate outlet.

2 . The method of claim 1 , wherein the acoustophoretic device further comprises at least one buffer inlet located between the solvent inlet and the at least one host-fluid inlet.

3 . The method of claim 2 , further comprising introducing a buffer into the flow chamber through the at least one buffer inlet, the buffer creating a buffer layer that permits the target cells to pass therethrough but destroys the non-target cells as they pass therethrough.

4 . The method of claim 3 , wherein the buffer is a selective lytic buffer.

5 . The method of claim 1 , further comprising removing a portion of the solvent from the device through the residual outlet.

6 . The method of claim 1 , wherein the piezoelectric material includes a plurality of piezoelectric elements arranged in an array, the plurality of piezoelectric elements operated between active and inactive modes such that the target cells are trapped above the piezoelectric elements in the active mode.

7 . The method of claim 6 , further comprising switching the piezoelectric elements between the active and inactive modes to move the target cells trapped in the acoustic standing wave along the longitudinal axis from the first end to the second end of the flow chamber to the particulate outlet.

8 . The method of claim 1 , wherein the solvent is a bacteria-friendly solvent.

9 . The method of claim 1 , wherein the acoustic standing wave is a multi-dimensional acoustic standing wave.

10 . The method of claim 1 , wherein acoustically active particles are attached to the target cells.

11 . An acoustophoretic device, comprising:
a flow chamber having a solvent inlet and at least one host-fluid inlet at a first end of the flow chamber, and a particulate outlet and at least one residual outlet at a second end of the flow chamber opposite the first end thereof, wherein the solvent inlet and the particulate outlet are aligned with a longitudinal axis of the flow chamber and the at least one host-fluid inlet and the at least one residual outlet are spaced apart from the longitudinal axis; at least one ultrasonic transducer located on a wall of the flow chamber, the at least one ultrasonic transducer including a piezoelectric material driven by a voltage signal to create an acoustic standing wave in the flow chamber; and a reflector located on a wall on the opposite side of the flow chamber from the at least one ultrasonic transducer.

12 . The acoustophoretic device of claim 11 , further comprising at least one buffer inlet located between the solvent inlet and the at least one host-fluid inlet.

13 . The acoustophoretic device of claim 11 , wherein the piezoelectric material includes a plurality of piezoelectric elements arranged in an array, the plurality of piezoelectric elements configured to operate between active and inactive modes.

14 . The acoustophoretic device of claim 11 , wherein the flow chamber is disposable.

15 . The acoustophoretic device of claim 11 , wherein the at least one ultrasonic transducer comprises:
a housing having a top end, a bottom end, and an interior volume; and a piezoelectric crystal at the bottom end of the housing having an exposed exterior surface and an interior surface, the crystal being able to vibrate when driven by a voltage signal.

16 . The acoustophoretic device of claim 15 , wherein no backing layer is present within the housing of the at least one ultrasonic transducer, and an air gap is present in the interior volume between the crystal and a top plate at the top end of the housing; or
wherein the at least one ultrasonic transducer further comprises a backing layer contacting the interior surface of the crystal, the backing layer being made of a substantially acoustically transparent material.

17 . A method for inspecting, detecting, isolating, monitoring, characterizing, or separating specialized circulating cells in blood containing blood cells, the method comprising:
flowing the blood containing specialized circulating cells and blood cells through an acoustophoretic device, the acoustophoretic device comprising:
a flow chamber having at least one inlet and at least one outlet;
at least one ultrasonic transducer located on a wall of the flow chamber, the at least one ultrasonic transducer including a piezoelectric material driven by a voltage signal to create an acoustic standing wave in the flow chamber; and
a cover glass forming a wall of the flow chamber opposite the at least one ultrasonic transducer;
sending a voltage signal to drive the at least one ultrasonic transducer to create the acoustic standing wave in the flow chamber and microbubbles in the blood, the microbubbles attaching to the specialized circulating cells and being driven by the acoustic standing wave toward the cover glass where the specialized circulating cells and attached microbubbles become trapped in the acoustic standing wave; and examining the specialized circulating cells using a microscope objective.

18 . The method of claim 17 , wherein the at least one inlet includes a solvent inlet and at least one host-fluid inlet at a first end of the flow chamber, and the at least one outlet includes a particulate outlet and at least one residual outlet at a second end of the flow chamber opposite the first end thereof, wherein the solvent inlet and the particulate outlet are aligned with a longitudinal axis of the flow chamber and the at least one host-fluid inlet and the at least one residual outlet are spaced apart from the longitudinal axis.

19 . The method of claim 18 , wherein the acoustophoretic device further comprises at least one buffer inlet located between the solvent inlet and the at least one host-fluid inlet.

20 . The method of claim 19 , further comprising introducing a dividing buffer into the flow chamber through the at least one buffer inlet.

21 . The method of claim 17 , wherein the acoustophoretic device further comprises a substantially acoustically transparent l

Assignees

• Flodesign Sonics Inc

Inventors

• Gilmanshin Rudolf
• Lipkens Bart

Classifications

• G01N33/575

  for cancer · CPC title

• B01L2200/025

  Align devices or objects to ensure defined positions relative to each other · 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

• G01N33/491 Primary

  by separating the blood components (G01N15/05 takes precedence) · CPC title

• B01D43/00

  Separating particles from liquids, or liquids from solids, otherwise than by sedimentation or filtration (flotation processes B03D1/00; drying solid materials or objects F26B) · CPC title