Abstract: In various embodiments, method and devices for delivering large cargos (e.g., organelles, chromosomes, bacteria, and the like) into cells are provided. In certain embodiments method of delivering a large cargo into eukaryotic cells, are provided that involve providing eukaryotic cells disposed on one side of a porous membrane; providing the cargo to be delivered in a solution disposed in a reservoir chamber on the opposite side of the porous membrane; and applying pressure to the reservoir chamber sufficient to pass the cargo through pores comprising said porous membrane wherein said cargo passes through cell membranes and into the cells.

Abstract: A novel Self-Locking Optoelectronic Tweezers (SLOT) for single microparticle manipulation across a large area is provided. DEP forces generated from ring-shape lateral phototransistors are utilized for locking single microparticles or cells in the dark state. The locked microparticles or cells can be selectively released by optically deactivating these locking sites.

Abstract: This invention provides novel tools for surgery on single cells and substrates/devices for delivery of reagents to selected cells. In certain embodiments the substrates comprise a surface comprising one or more orifices, where nanoparticles and/or a thin film is deposited on a surface of said orifice or near said orifice, where the nanoparticles and/or a thin film are formed of materials that heat up when contacted with electromagnetic radiation. In certain embodiments the pores are in fluid communication with microchannels containing one or more reagents to be delivered into the cells.

Abstract: Methods and devices for the formation of droplets of a first fluid in a second fluid and the encapsulation of particles or cells within such droplets are disclosed. Impetus for droplet formation is provided by the creation of a transient bubble, which may be induced using a pulsed laser. Droplet volume and the frequency at which droplets are formed can be controlled by modulation of the pulsed laser. The disclosed methods and devices are particularly suitable for use in microfluidic devices.

Abstract: In certain embodiments this invention provides a pulsed-laser triggered microfluidic switching mechanism that can achieve a switching time of 70 ?s. This switching speed is two orders of magnitude shorter than that of the fastest switching mechanism utilized in previous ?FACS.

Abstract: Methods and devices for the formation and/or merging of droplets in microfluidic systems are provided. In certain embodiments a microfluidic droplet merger component is provided that comprises a central channel comprising a plurality of elements disposed and spaced to create a plurality of lateral passages that drain a carrier fluid out of a fluid stream comprising droplets of a first fluid contained in the carrier fluid; and a deformable lateral membrane valve disposed to control the width of said center channel.

Abstract: In various embodiments a plasmonic cell force sensor platform is provided where the platform comprises a plurality of micropillars, where micropillars comprising the plurality of micropillars each have a nanoparticle (e.g., a plasmonic nanoparticle, a fluorescent nanoparticle, etc.) disposed at the tip.

Abstract: Methods and devices for the formation and/or merging of droplets in microfluidic systems are provided. In certain embodiments a microfluidic droplet merger component is provided that comprises a central channel comprising a plurality of elements disposed and spaced to create a plurality of lateral passages that drain a carrier fluid out of a fluid stream comprising droplets of a first fluid contained in the carrier fluid; and a deformable lateral membrane valve disposed to control the width of said center channel.

Abstract: In various embodiments a Massively parallel Single-cell Electroporation Platform (MSEP) for low voltage, high efficiency delivery of extracellular materials into mammalian cells at an ultrahigh throughput of 10 million cells/min on a 1 cm2 chip is provided. In certain embodiments MSEP is realized by a 3D silicon-based device with, e.g., 5,000 short vertical microfluidic channels in parallel. Single cells flowing through these channels are geometrically confined to regions with intense and localized electric fields where cells are electroporated. High efficiency delivery of calcium dyes, large-sized dextran proteins, and plasmids into mammalian cells to establish a range of sizes and compositions have been successfully accomplished with MSEP.

Abstract: A 3-dimensional PDMS cell sorter having multiple passages in a PDMS layer that follow the same path in a DEP separation region and that are in fluid communication with each other within that region. The passages may differ in width transverse to the flow direction within the passages. Flat plates may sandwich the PDMS layer; each plate may have a planar electrode used to generate a DEP field within a sample fluid flowed within the passages. The DEP field may concentrate target cells or particulates within one of the passages within the DEP separation region. The passages may diverge after the DEP-separation region, leaving one passage with a high concentration of target cells or particulates. Techniques for manufacturing such structures, as well as other micro-fluidic structures, are also provided.

Abstract: In various embodiments methods and devices are provided for focusing and/or sorting particles and/or cells in a microfluidic channel. In certain embodiments the device comprises a microfluidic channel comprising a plurality of electrodes disposed to provide dielectrophoretic (DEP) forces that are perpendicular to hydrodynamic flows along the channel; wherein said device is configured to apply voltages to said electrodes to provide an electric field minimum that is not centered in said microfluidic channel.

Abstract: A 3-dimensional PDMS cell sorter having multiple passages in a PDMS layer that follow the same path in a DEP separation region and that are in fluid communication with each other within that region. The passages may differ in width transverse to the flow direction within the passages. Flat plates may sandwich the PDMS layer; each plate may have a planar electrode used to generate a DEP field within a sample fluid flowed within the passages. The DEP field may concentrate target cells or particulates within one of the passages within the DEP separation region. The passages may diverge after the DEP-separation region, leaving one passage with a high concentration of target cells or particulates. Techniques for manufacturing such structures, as well as other micro-fluidic structures, are also provided.

Abstract: A novel Self-Locking Optoelectronic Tweezers (SLOT) for single microparticle manipulation across a large area is provided. DEP forces generated from ring-shape lateral phototransistors are utilized for locking single microparticles or cells in the dark state. The locked microparticles or cells can be selectively released by optically deactivating these locking sites.

Abstract: In various embodiments methods are provided for delivering an agent of interest (e.g., protein, antibody, nucleic acid) into cells. In certain embodiments the method comprises contacting the cells with anisotropic magnetic particles in the presence of the agent; and applying a substantially uniform magnetic field to said magnetic particles where movement of said particles induced by said magnetic field introduces transient openings into said cell facilitating entry of said agent of interest into said cells.

Abstract: In various embodiments, method and devices for delivering large cargoes (e.g., organelles, chromosomes, bacteria, and the like) into cells are provided. In certain embodiments method of delivering a large cargo into eukaryotic cells, are provided that involve providing eukaryotic cells disposed on one side of a porous membrane; providing the cargo to be delivered in a solution disposed in a reservoir chamber on the opposite side of the porous membrane; and applying pressure to the reservoir chamber sufficient to pass the cargo through pores comprising said porous membrane wherein said cargo passes through cell membranes and into the cells.

Abstract: In certain embodiments this invention provides a pulsed-laser triggered microfluidic switching mechanism that can achieve a switching time of 70 ?s. This switching speed is two orders of magnitude shorter than that of the fastest switching mechanism utilized in previous ?FACS.

Abstract: Methods and devices for the formation of droplets of a first fluid in a second fluid and the encapsulation of particles or cells within such droplets are disclosed. Impetus for droplet formation is provided by the creation of a transient bubble, which may be induced using a pulsed laser. Droplet volume and the frequency at which droplets are formed can be controlled by modulation of the pulsed laser. The disclosed methods and devices are particularly suitable for use in microfluidic devices.

Abstract: Microfluidic devices in which electrokinetic mechanisms move droplets of a liquid or particles in a liquid are described. The devices include at least one electrode that is optically transparent and/or flexible.

Abstract: Methods and devices for the formation and/or merging of droplets in microfluidic systems are provided. In certain embodiments a microfluidic droplet merger component is provided that comprises a central channel comprising a plurality of elements disposed and spaced to create a plurality of lateral passages that drain a carrier fluid out of a fluid stream comprising droplets of a first fluid contained in the carrier fluid; and a deformable lateral membrane valve disposed to control the width of said center channel.

Abstract: Methods, devices, and systems are provided for the delivery of agents (e.g., nucleic acids, proteins, organic molecules, organelles, antibodies or other ligands, 5 etc.) into live cells and/or the extraction of the same from said cells. In various embodiments the photothermal platforms and systems incorporating such photothermal platforms are provided that permit efficient, high-throughput cargo delivery into live cells.