Selective and high-resolution printing of single cells
Inventors
Abate, Adam R. • Zhang, Pengfei • Cole, Russell
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12644113-B2
Publication Date
2026-06-02
Expiration Date
Abstract
Methods for on-demand printing discrete entities including, e.g., cells, media or reagents to substrates are provided. In certain aspects, the methods include manipulating qualities of the entities or biological components thereof. In some embodiments, the methods may be used to create arrays of microenvironments and/or for two and three-dimensional printing of tissues or structures and/or for in situ printing for microsurgeries. Systems and devices for practicing the subject methods are also provided.
Core Innovation
A microfluidic delivery method delivers a plurality of discrete entities to a substrate by flowing the discrete entities through an air flow via a microfluidic device comprising an air/liquid co-flow junction. One or more air channels connected to the junction apply the air flow, and the air flow and one or more of the plurality of discrete entities are directed through the air/liquid co-flow junction toward the substrate.
The discrete entities are affixed to the substrate after delivery via a force selected from a gravitational force, an electrical force, a magnetic force, and combinations thereof. The document further describes delivery of droplets via the microfluidic air/liquid co-flow junction and affixing droplets to a substrate surface using gravitational, electrical, and/or magnetic forces.
Additional embodiments describe microdroplet sorting connected to the delivery workflow, including sorting based on optical detection/scan and electric-field based sorting. The document also describes reagent addition, recovery and manipulation of affixed droplets, multilayer 2D/3D tissue or wound-layer printing, cell printing with detection at multiple time points, and spheroid formation.
Claims Coverage
The independent claim set is centered on a method of delivering discrete entities to a substrate using a microfluidic device with an air/liquid co-flow junction, wherein an air flow is applied and directed through the junction, and the entities are affixed using a selected force. The inventive features are further limited by dependent claims that introduce quantitative size/volume constraints, upstream sorting using a microfluidic sorter, and discrete entity types such as droplets formed with a selectively activatable droplet maker.
Air/liquid co-flow junction for air-flow driven delivery
flowing a plurality of discrete entities through an air flow via a microfluidic device comprising an air/liquid co-flow junction connected to one or more air channels through which the air flow can be applied
Directing air flow and discrete entities through the junction to the substrate
directing the air flow and one or more of the plurality of discrete entities through the air/liquid co-flow junction to the substrate
Affixing to the substrate using a selected force
affixing the one or more of the plurality of discrete entities to the substrate via a force, wherein the force is selected from a gravitational force, an electrical force, a magnetic force, and combinations thereof
Discrete entities size constraint
the discrete entities have a diameter of about 1 to 1000 μm
Discrete entities volume constraint
the discrete entities have a volume within about 1 femtoliter to about 1000 nanoliters
Upstream sorting before co-flow delivery
a microfluidic device comprising a sorter to sort discrete entities before delivering them through an air/liquid co-flow junction to a substrate
Optical-scan-based sorting
sorting is performed based on results from an optical scan
Droplet delivery formed by a selectively activatable droplet maker
the discrete entities are droplets formed using a selectively activatable droplet maker in a microfluidic device, with droplets formed by selectively activating the droplet maker
Overall claim coverage emphasizes air/liquid co-flow junction delivery of discrete entities using an applied air flow, deposition to a substrate via affixing using gravitational, electrical, or magnetic force, and dependent refinements that include discrete entity size/volume ranges, optional upstream microfluidic sorting, and droplet formation using a selectively activatable droplet maker.
Stated Advantages
Enables high-accuracy/high-viability sorting and single-cell sorting viability, as described in the document summary.
Supports micro-to-nanoscale single-cell printing/patterning and spheroid formation, as described in the document summary.
Documented Applications
On-demand, high-resolution printing of discrete entities, notably single cells, to a substrate using a microfluidic air/liquid co-flow junction.
Microdroplet sorting with recovery and manipulation of affixed droplets using optical detection/scan and electric-field deflection, as described in the document summary.
Multilayer 2D/3D tissue or wound-layer printing, as described in the document summary.
Cell printing with detection at multiple time points, and reagent addition and merging/coalescence, as described in the document summary.
Spheroid formation, as described in the document summary.
Interested in licensing this patent?