Microfluidic laser-activated intracellular delivery systems and methods
Inventors
Wagner, Matthias • Madrid, Marinna
Assignees
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Publication Number
US-11643667-B2
Publication Date
2023-05-09
Expiration Date
Abstract
An intracellular delivery system and method are provided. The intracellular delivery system comprises a laser-activated surface and cells positioned at a distance from the laser-activated surface. A laser provided a laser pulse that is used to porate membranes of the cells to deliver or extract cargo from the cells into a liquid surrounding the cells. The method of intracellular delivery comprises positioning a laser-activated surface at a distance from cells and applying a laser pulse from the laser to the surface to porate membranes of the cells to deliver or extract cargo from the cells into a liquid surrounding the cells.
Core Innovation
The invention provides an intracellular delivery system comprising a laser-activated surface and cells positioned at a distance from the laser-activated surface. A laser provides a laser pulse that enables the cells to import or export cargo from or to a medium surrounding the cells, and contrast-agent microbubbles support the laser-activated delivery.
In a further refinement, the invention includes a first set of laser-generated contrast-agent microbubbles and a second set of laser-generated contrast-agent microbubbles. The first set of laser-generated contrast-agent microbubbles is imploded by the second set of laser-generated contrast-agent microbubbles, and this microbubble interaction is used together with the laser-activated surface and the cells at a distance to enable cargo import or export from or to the surrounding medium.
The system further encompasses laser-activated surfaces including patterned layers of thin layer of metal, polymer materials, ink-containing polymers, and oxide layer materials, with spatial control features that promote nucleation of the bubbles at pre-determined sites responsive to absorbing the radiation from the laser pulse. The disclosed laser pulse is provided by an optical source selected from diode-pumped solid state lasers, lamp-pumped solid state lasers, gas lasers, fiber lasers, diode lasers, or quantum cascade lasers.
Claims Coverage
The provided independent claims are clm-00001 and clm-00020, and they define a laser-activated, distance-based intracellular import/export system with contrast-agent microbubbles, including a microbubble implosion interaction between two bubble sets in clm-00020. Across these claims, the coverage focuses on the combination of a laser-activated surface, cells positioned at a distance from that surface, a laser pulse enabling cargo import or export, and contrast-agent microbubbles as part of the delivery system, with clm-00020 adding the first-set/second-set implosion relationship.
Laser-activated surface for distance intracellular cargo import/export
A laser-activated surface; cells positioned at a distance from the laser-activated surface; a laser providing a laser pulse that enables the cells to import or export cargo from or to a medium surrounding the cells; and contrast-agent microbubbles.
Implosion of first bubble set by second bubble set
A laser-activated surface; cells positioned at a distance from the laser-activated surface; a laser providing a laser pulse that enables the cells to import or export cargo from or to a medium surrounding the cells; and a first set of laser-generated contrast-agent microbubbles and a second set of laser-generated contrast-agent microbubbles, wherein the first set of laser-generated contrast-agent microbubbles is imploded by the second set of laser-generated contrast-agent microbubbles.
Laser pulse optical source types
The laser pulse is provided by an optical source selected from diode-pumped solid state lasers, lamp-pumped solid state lasers, gas lasers, fiber lasers, diode lasers, or quantum cascade lasers.
Patterned laser-activated surface material layer
The laser-activated surface comprises a patterned layer of material selected from thin layer of metal, polymer materials, ink-containing polymers, and an oxide layer.
Pre-determined sites for bubble nucleation
The features promote nucleation of the bubbles at pre-determined sites responsive to absorbing the radiation from the laser pulse.
Selective targeting of the laser-activated surface
The laser-activated surface is selectively targeted to porate specific cells.
Cargo selection list
The cargo is selected from a group including CRISPR-associated endonuclease Cas components, guide ribonucleic acid, ssODN, mRNA or pre-mRNA, siRNA, shRNA, microRNA, proteins and enzymes, antibodies and nanobodies, and particles including nanoparticles, quantum dots, radionuclide, and magnetic beads, among other listed cargo types.
The claim coverage centers on a distance-based intracellular delivery approach using a laser-activated surface with a laser pulse enabling cargo import/export and contrast-agent microbubbles. The second independent claim adds a specific microbubble implosion relationship between two sets of laser-generated contrast-agent microbubbles. Dependent coverage shown in the provided claims further specifies laser source types, patterned laser-activated surface materials, selective poration targeting, predetermined bubble nucleation sites, and an explicit cargo selection list.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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