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US 9,885,059 B2Granted
Ultrahigh throughput microinjection device
AssigneesIndiana University Research and Technology Corporation, The Regents of the University of California
InventorsChris Ballas, Masa Rao, Yanyan Zhang
Life of this patent
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Abstract
Many applications in cell biology, genetic engineering, cell-based therapeutics, and drug discovery require precise and safe methods for introducing membrane-impermeable molecules into cells. This can be implemented satisfactorily by microinjection. However, disadvantages of traditional manual microinjection include high degree of operator skill, low throughput and labor-intensiveness. Many studies have focused on developing automated and high-throughput systems for microinjection to address these limitations. However, none have provided sufficient throughput for applications such as ex vivo cell therapy, where manipulation of many cells is helpful.
Claims24
An apparatus for manipulation of biological cells, comprising:
- a substrate having a surface and a plurality of wells,
- each said well having a boundary shape at the surface adapted and configured to support thereon a cell,
- each said well having a bottom and including a projection extending from the bottom toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and/or wall of the cell,
- a single common fluid flow channel that is fluidly in direct contact with each of the plurality of wells, wherein the fluid flow channel is capable of exposing each of the plurality of wells to biological cells in a simultaneous manner, and wherein the fluid flow channel can be fluidly connected to a first source of fluid, and
- a plurality of aspiration vias that have unobstructed access to each of the wells and to a cell bound at the boundary shape of the wells, wherein the plurality of aspiration vias are fluidly connected to a second source of fluid, to which negative pressure can be applied to provide suction that captures the cell, or to which positive pressure can be applied to release the cell, wherein the plurality of aspiration vias are fluidly in contact with other wells in said plurality of wells, wherein a pressure in each of the aspiration vias is capable of being directly applied to a cell membrane of a cell captured at the boundary shape, wherein the pressure in each of the aspiration vias is capable of being varied in relation to the pressure in the common fluid flow channel, wherein the plurality of aspiration vias is configured to provide uniform tension on the cell membrane of a cell captured at the boundary shape, wherein the plurality of aspiration vias are located in the bottom of each of said wells and wherein at least two of the plurality of aspiration vias are located opposite one another and separated by the projection and whose axis are substantially perpendicular to the surface.
2 more elements
An apparatus for manipulation of biological cells, comprising:
- a substrate having a surface, one or more inlet ports and one or more outlet ports that extend entirely through the thickness of the substrate, and a plurality of wells,
- wherein each of the plurality of wells has an interior adapted and configured to hold therein at least a portion of a cell,
- wherein each of the plurality of wells comprises a plurality of aspiration vias that have unobstructed access to each of the wells and to a cell bound at a boundary shape of the wells, wherein the plurality of aspiration vias are fluidly in contact with other wells in said plurality of wells, wherein a pressure in each of the aspiration vias is capable of being directly applied to a cell membrane of a cell captured at the boundary shape, wherein the pressure in each of the aspiration vias is capable of being varied in relation to the pressure in the common fluid flow channel, wherein the plurality of aspiration vias is configured to provide uniform tension on the cell membrane of a cell captured at the boundary shape, wherein the plurality of aspiration vias are located in the bottom of each of said wells and wherein at least two of the plurality of aspiration vias are located opposite one another and separated by the projection and whose axis are substantially perpendicular to the surface, and
- a projection extending from a bottom of each of the wells toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and/or wall of the cell,
- a cover plate comprising a fluid flow channel, wherein the fluid flow channel can be fluidly connected with the one or more inlet ports, the one or more outlet ports and the plurality of wells of the substrate;
- a fluid inlet flow channel that can be fluidly connected with the one or more inlet ports and which can be fluidly connected with a first source of fluid;
- and
- a fluid outlet flow channel that is in fluid communication with the one or more outlet ports.
5 more elements
Dependencies are inferred from the claim text.