Microfluidic devices for optically-driven convection and displacement, kits and methods thereof

Inventors

Kurz, Volker L. S. • Lionberger, Troy A. • Sackmann, Eric K. • Szeto, Kai W. • Lebel, Paul M. • Bruhn, Brandon R. • Breinlinger, Keith J. • Hobbs, Eric D. • McFarland, Andrew W. • Nevill, J. Tanner • Wang, Xiaohua

Assignees

Bruker Cellular Analysis Inc

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Publication Number

US-11802264-B2

Patent

Publication Date

2023-10-31

Expiration Date


Abstract

Apparatuses and methods are described for the use of optically driven bubble, convective and displacing fluidic flow to provide motive force in microfluidic devices. Alternative motive modalities are useful to selectively dislodge and displace micro-objects, including biological cells, from a variety of locations within the enclosure of a microfluidic device.

Core Innovation

The disclosed microfluidic approach dislodges one or more micro-objects within a microfluidic device by illuminating a selected discrete region containing or adjacent to the micro-objects. The microfluidic device includes an enclosure having a microfluidic circuit with a flow region and at least one sequestration pen, and the sequestration pen comprises a connection region, an isolation region, and a displacement force generation region.

The connection region includes a proximal opening to the flow region and a distal opening to the isolation region. The fluidic connection between the isolation region and the displacement force generation region is configured to prevent passage of a micro-object from the isolation region to the displacement force generation region, and maintaining illumination of the selected discrete region for a first period of time sufficient to generate a dislodging force dislodges the micro-objects from a surface of the microfluidic device.

The disclosure further describes illumination-based mechanisms for generating displacement forces, including cavitation forces created by heating a first portion of a fluidic medium to cavitate, persistent gaseous bubble formation that displaces fluid around micro-objects, and convective flow attributed to thermocapillary convection (Gibbs-Marangoni effect) driven by temperature gradients from illumination. Microfluidic architectures are described with regions for isolation and displacement force generation, including cyclic culturing pen geometries and passive features that nucleate or guide bubbles and interfaces.

Claims Coverage

The independent claim identified is clm-00001. It includes two core inventive areas: optically illuminating a selected discrete region to generate a dislodging force, and using a sequestration pen architecture with connection, isolation, and displacement force generation regions configured to prevent micro-object passage.

Illumination of a selected discrete region to generate a dislodging force

Illuminating a selected discrete region containing or adjacent to one or more micro-objects disposed within a fluidic medium in an enclosure of the microfluidic device, wherein maintaining the illumination of the selected discrete region for a first period of time sufficient to generate a dislodging force dislodges the one or more micro-objects from a surface of the microfluidic device.

Sequestration pen with connection, isolation, and displacement force generation regions

Providing at least one sequestration pen comprising a connection region, an isolation region, and a displacement force generation region, wherein the connection region comprises a proximal opening to the flow region and a distal opening to the isolation region and wherein a fluidic connection between the isolation region and the displacement force generation region is configured to prevent passage of a micro-object from the isolation region to the displacement force generation region.

Across clm-00001, the claim coverage centers on dislodging micro-objects via illumination of a selected discrete region for a sufficient first period of time, while employing a sequestration pen architecture with connection, isolation, and displacement force generation regions that prevents micro-object passage.

Stated Advantages

Enables dislodging of one or more micro-objects from a surface of the microfluidic device using illumination that generates a dislodging force maintained for a first period of time.

Controls micro-object transport within the microfluidic enclosure by configuring the sequestration pen to prevent passage of a micro-object from the isolation region to the displacement force generation region.

Allows dislodging one or more micro-objects from a surface of a microfluidic device.

Documented Applications

Dislodging and displacing micro-objects, including biological cells, within a microfluidic device using optically driven bubble, cavitation, and flow mechanisms to support removal from a surface.

Displacement and export/positioning of human hybridoma cells using optically generated bubbles, with assessment of viability/proliferation [procedural detail omitted for safety].

Cyclic Marangoni-effect flow demonstrations using polystyrene beads in patterned/cyclic pen geometries.

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