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US 10,589,272 B2Granted
Thermally-assisted acoustic separation of cells based on their stiffness
AssigneeThe Florida International University Board of Trustees
InventorsBilal El-Zahab, Ata Dolatmoradi
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Abstract
Devices, systems, and methods for separating cells or vesicles using a thermo-acoustophoretic approach are provided. A microfluidic device can be used for stiffness-based separation of cells or vesicles that otherwise have the same or approximately the same size, shape, and charge, where at least some of the membranes or vesicles have different compositions. The separation can be done by tuning the temperature of the cells or vesicles.
Claims18
A method of separating vesicles, the method comprising:
- providing to a microfluidic device a population of vesicles suspended in an aqueous medium, the vesicles having the same or approximately the same size, shape, and charge but different stiffness due to different compositions;
- applying standing-wave acoustic signals to the microfluidic device, the acoustic signals being set to a pre-determined first harmonic frequency of the vesicles suspended in the aqueous medium;
- and
- tuning the temperature of the device to separate vesicles based on their directions of migration as a response to the acoustic signals,
- each vesicle comprising a lipid bilayer membrane and that the compressibility of vesicles changes at a temperature TΦ characteristic to the stiffness of said vesicles in the presence of the acoustic field, and
- the microfluidic device comprising:
- a microfluidic channel etched on a silicon wafer, the channel comprising an inlet and at least one outlet, the inlet and the at least one outlet being controlled by their respective syringe pump for fluid transport, and if more than one outlet is present, the outlets being separated by a thermally insulating material;
- an optically transparent cover slip placed atop the microfluidic channel;
- at least one acoustic transducer bonded to the back of the microfluidic channel and connected to an AC signal generator and if more than one acoustic transducer is present, each transducer being connected to an independent signal generator;
- at least one thermoelectric transducer positioned in thermal contact with the microfluidic channel, the at least one thermoelectric transducer being capable of controlling the temperature of the channel and if more than one thermoelectric transducer is present, each transducer being operated independently;
- and
- a heat sink disposed underneath the at least one thermoelectric transducer.
9 more elements
A method of separating vesicles, the method comprising:
- providing a microfluidic device for separating vesicles, the device comprising:
- a microfluidic channel etched on a silicon wafer, the channel comprising inlet and at least one outlet, the inlet and the at least one outlet being controlled by their respective syringe pump for fluid transport, and if more than one outlet is present, the outlets being separated by a thermally insulating material;
- an optically transparent cover slip placed atop the microfluidic channel;
- at least one acoustic transducer bonded to the back of the microfluidic channel and connected to an AC signal generator, and if more than one acoustic transducer is present, each transducer being connected to an independent signal generator;
- at least one thermoelectric transducer positioned in thermal contact with the microfluidic channel, the at least one thermoelectric transducer being capable of controlling the temperature of the channel, and if more than one thermoelectric transducer is present, each transducer being, operated independently;
- and
- an aluminum heat sink disposed underneath the at least one thermoelectric transducer;
- providing a population of vesicles suspended in an aqueous medium into the inlet of the device using a syringe pump operating in injection mode, the vesicles having the same or approximately the same size, shape, and charge but at least two distinctly different membrane compositions;
- applying to the device standing-wave acoustic signals via a first transducer, the acoustic signals being set to a pre-determined first harmonic frequency of the vesicles suspended in the aqueous medium;
- tuning the temperature within the channel by controlling a first Peltier element to separate vesicles based on their directions of migration as a response to the acoustic signals;
- collecting the separated vesicles from the channel using a syringe pump operating in withdrawal mode from a first outlet;
- and
- repeating said process until all vesicles are separated,
- each vesicle comprising a lipid bilayer membrane and that the compressibility of vesicles changes at a temperature TΦ characteristic to the composition of said vesicles in the presence of the acoustic field.
11 more elements
Dependencies are inferred from the claim text.