Method and apparatus for temperature gradient microfluidics
Inventors
Yang, Tinglu • Rogers, Bradley • Zhang, Jifeng • Cremer, Paul S.
Assignees
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Publication Number
US-11971377-B2
Publication Date
2024-04-30
Expiration Date
Abstract
The present invention describes a versatile, robust and environmentally controlled platform with a linear temperature gradient for massively parallel chemical or biochemical processing. This apparatus is capable of probing the phase transition behavior of macromolecules in solution, both thermodynamically and kinetically. This includes—but is not limited to—liquid/liquid phase transition behavior of antibody solutions and in situ gelation of thermo-responsive polymers. The device can be operated in a multiplex fashion using a controlled temperature gradient architecture and visualized by dark field microscopy or by other optical intensity measurements.
Core Innovation
The invention describes a temperature gradient device that includes a planar, horizontally oriented base with a first thermoelectric cooler and a second thermoelectric cooler positioned on the base at a distance from one another. Each thermoelectric cooler has a hot surface and a cold surface, and the sample holder is separated from the first and second thermoelectric coolers and configured to move into contact with a first end on the first thermoelectric cooler and a second opposing end on the second thermoelectric cooler.
A chamber secured to the base encloses the first thermoelectric cooler, the second thermoelectric cooler, and the sample holder, and a lid is configured to seal the chamber. A flexible element attached to the lid is configured to suspend the sample holder above the first and second thermoelectric coolers while maintaining an open chamber in a lifted state, and to lower the sample holder for simultaneous contact with the first and second thermoelectric coolers while sealing the chamber in a lowered state.
The platform supports temperature gradient microfluidic probing of macromolecular phase transitions by combining the gradient device with microfluidic sample holders such as channels, capillary arrays, and well arrays sealed in a climate-controlled chamber. The chamber enables environmentally controlled conditions, including gas inlet and gas outlet and humidity, temperature, and tilt sensing, and phase behavior is visualized using dark-field microscopy and/or other optical modalities, including fluorescence, spectroscopic approaches, and hyperspectral imaging.
Claims Coverage
The document includes one independent claim directed to a temperature gradient device architecture. The independent claim centers on two spatially separated thermoelectric coolers on a planar base, coupled to a movable sample holder that can be simultaneously lowered into contact with both thermoelectric coolers while the chamber is sealed by a lid attached to a flexible suspension element.
Two spatially separated thermoelectric coolers on a planar base
The device includes a planar, horizontally oriented base with a first thermoelectric cooler positioned on the base and a second thermoelectric cooler positioned on the base a distance away from the first thermoelectric cooler, with hot and cold surfaces arranged so the device can establish a temperature gradient.
Movable sample holder for simultaneous contact with both thermoelectric coolers
A sample holder separated from the first and second thermoelectric coolers is configured to move into contact with a first end on the first thermoelectric cooler and a second opposing end on the second thermoelectric cooler.
Sealed chamber with a lid that suspends and lowers the sample holder
A chamber secured to the base encloses the first thermoelectric cooler, the second thermoelectric cooler, and the sample holder, and includes a lid configured to seal the chamber; the lid is attached to a flexible element that suspends the sample holder above the first and second thermoelectric coolers in a lifted open state and lowers the sample holder for simultaneous thermoelectric cooler contact while sealing the chamber in a lowered state.
Independent claim coverage focuses on a temperature gradient device that uses two spatially separated thermoelectric coolers mounted on a planar base, with a movable sample holder lowered into simultaneous contact with both thermoelectric coolers while a lid-and-flexible-element mechanism keeps the chamber open in a lifted state and sealed in a lowered state.
Stated Advantages
Enables massively parallel, environmentally controlled probing of macromolecular phase transitions across a temperature gradient.
Enables simultaneous detection across the gradient, supporting kinetic and thermodynamic measurements.
Provides reduced convection and reduced condensation effects via chamber humidity control and leveling.
Supports small sample volumes and fast establishment of the temperature gradient for early-time measurement.
Documented Applications
Probing macromolecular phase transitions, including liquid-liquid phase separation (LLPS) and in situ gelation, using microfluidic sample holders.
Performing cloud point measurements and related phase-transition characterization of thermoresponsive polymers, including protein-rich droplets and aqueous two-phase systems (ATPS).
Measuring DNA melting curves using a specified intercalation dye (SYBR Green I).
Investigating protein crystallization using multidimensional arrays as described in the document.
Visualizing phase behavior with dark-field microscopy and/or other optical modalities including hyperspectral imaging and selectable microscopy technologies.
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