Abstract: The present disclosure relates to a biocompatible, in vitro probe system. The probe system may have a substrate and a culture well supported on the substrate. The culture well defines a three-dimensional volume for containing in vitro cultures of electroactive cells. The probe system has at least one probe subsystem supported on the substrate. The probe subsystem has at least one probe having an array of electrodes, with the probe being disposed within the culture well for in vitro electrically communicating with the electroactive cells. The probe subsystem is adapted to be interfaced to an external instrumentation/recording device.

Abstract: Arrays of single molecules and methods of producing an array of single molecules are described. Arrays with defined volumes between 10 attoliters and 50 picoliters enable single molecule detection and quantitation.

Abstract: A system, device and method for electroporation of living cells and the introduction of selected molecules into the cells utilizes a fluidic system where living cells and biologically active molecules flow through a channel that exposes them to electric fields, causing the molecules to be transferred across the cell membrane. The device is structured in a manner that allows precise control of the cells location, motion, and exposure to electric fields within the flow channel device. The method is particularly well suited for the introduction of DNA, RNA, drug compounds, and other biologically active molecules into living cells.

Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing. Such polynucleotide processing may be useful for a variety of applications, including polynucleotide sequencing.

Abstract: The invention is directed to disposable cartridge for electroporation of cells, comprising a fluid compartment in an interior of the disposable cartridge; a first fluid port for providing cell suspension to the fluid compartment, and a second fluid port for delivering a fluid comprising at least one compound to be electroporated into the cells to the fluid compartment; a first electrode and a second electrode disposed in the fluid compartment; at least one exit port which delivers the fluid from the fluid compartment wherein the first and second fluid port have a fluid communication to a mixing channel which has a fluid communication to the fluid compartment, and a third ground electrode and a fourth ground electrode.

Abstract: A “localizable” systemic gene therapy system is provided substantially increasing the transfection efficiency of the gene vectors into targeted tissue cells and substantially reducing the escape of the gene vectors from the targeted tissue volume, such as would waste the vectors, promote undesired immune reactions, and/or incur prohibitive costs for the required dose of gene-containing virus vectors. In this regard, the invention provides a means to simultaneously achieve local electroporation and gene-containing vector injection in a portion of a vascularized organ. It includes two double-balloon catheters that create contained volumes in parallel blood vessels for the introduction of vectors with reduced loss along with electrodes providing electroporation of the cells in the same location where the vectors are injected.

Abstract: Disclosed is an apparatus and associated method for tagging insects and arthropods. According to an exemplary embodiment of this disclosure, an electrosprayer is provided including a nozzle cartridge, a spray chamber removably attached to the nozzle cartridge and a power supply operatively connected to the nozzle cartridge and a grounding plate within the spray chamber to electrically charge droplets expelled from the nozzle which coat one or more insects contained in the spray chamber.

Abstract: A method of inducing local cell death in patient tissue is provided. The method includes generating first and second radiation, conveying the radiation to a focusing element, and focusing the radiation on a target with the focusing element. A system for inducing local cell death in patient tissue is also provided. The system includes a power source for generating narrowband and/or ultra-wideband radiation, and a focusing element for focusing the radiation on a target.

Abstract: Arrays of single molecules and methods of producing an array of single molecules are described. Arrays with defined volumes between 10 attoliters and 50 picoliters enable single molecule detection and quantitation.

Abstract: An object of the invention is to provide an electroporation method for treating vesicles with exogenous material for insertion of the exogenous material into the vesicles which includes the steps of: a. retaining a suspension of the vesicles and the exogenous material in a treatment volume in a chamber which includes electrodes, wherein the chamber has a geometric factor (cm.sup.?1) defined by the quotient of the electrode gap squared (cm.sup.2) divided by the chamber volume (cm.sup.3), wherein the geometric factor is less than or equal to 0.1 cm.sup.?1, wherein the suspension of the vesicles and the exogenous material is in a medium which is adjusted such that the medium has conductivity in a range spanning 50 microSiemens/cm to 500 microSiemens/cm, wherein the suspension is enclosed in the chamber during treatment, and b. treating the suspension enclosed in the chamber with one or more pulsed electric fields.

Abstract: A cell treatment device which allows cell dispersion liquid including cancer cells to pass therethrough to cause at least the cancer cells to be subjected to at least one of a physical action, a chemical action, and a biologically activating action, includes: a slit member having a first surface and a second surface and including a through hole having a slit shape penetrating from the first surface to the second surface and extending in one direction, the through hole having a tapered portion, wherein the width of a cross section of the tapered portion orthogonal in the one direction reduces from the first surface toward the second surface side, and is smaller than an average diameter of the cancer cells at an end on the second surfaces side, and the cell dispersion liquid is allowed to pass from the first surface side through the through hole to the second surface side.

Abstract: Described herein are methods and compositions for high efficiency transfection of siRNA into a cell population. Such methods and compositions utilize a low voltage pre-conditioning pulse to modulate the efficiency of siRNA transfection. In some embodiments, the methods and compositions permit spatial and temporal control of siRNA transfection efficiency within a population of cells. The disclosed methods and compositions, in some embodiments, are amenable to high throughput applications such as siRNA library-based phenotypic screening.

Abstract: Devices, systems and methods for processing cellulosic material to produce fermentable sugars are provided. Devices, systems and methods for increasing fermentation rates of microbes via biostimulation are provided. Electrodes are preferably positioned along an interior or exterior of a tube-shaped component to administer electromagnetic/electric pulses to a solution comprising a microbe. Systems can advantageously be used in new biofuels production plants, or in existing biofuels production plants without the need for significant retrofits.

Abstract: An apparatus for electroporation of biological cells is provided. The apparatus includes a sample container having an insulator chamber for holding the cells. The sample container has a first electrode and a second electrode to provide electrical connection for electroporation. The insulator chamber is configured to contain at least one cell monolayer. The apparatus also includes a pulse generator that can generate a predetermined pulse for electroporation of the cells.

Abstract: It is intended to provide an object-holding sheet and an object-treating equipment, which are useful for arranging objects such as biological materials (e.g., cells, embryos or individuals) or particles having the similar size thereto and efficiently conducting procedures such as analysis and fractionation on the objects. The present invention provides an object-holding sheet for holding two or more objects, the object-holding sheet including: a sheet member having two or more through-holes; and an anti-drop member corresponding to each of the holes, wherein the holes have a size that enables only one of the objects to be held, and the anti-drop member is disposed in the vicinity of one opening of each of the holes so as not to permit the object held in each of the holes to pass through the opening.

Abstract: Devices, systems and methods for processing cellulosic material to produce fermentable sugars are provided. Devices, systems and methods for increasing fermentation rates of microbes via biostimulation are provided. Electrodes are preferably positioned along an interior or exterior of a tube-shaped component to administer electromagnetic/electric pulses to a solution comprising a microbe. Systems can advantageously be used in new biofuels production plants, or in existing biofuels production plants without the need for significant retrofits.

Abstract: An object of the present invention is to provide a screening system that targets ion channels and has superior efficiency. The present invention provides a material for screening for compounds that act on a target ion channel, comprising cells which retain at least one first DNA encoding a voltage-dependent Na ion channel that has been inhibited from being inactivated, and in which a K ion channel has been activated so that a resting membrane potential becomes deeper in a negative direction.

Abstract: A glass pipette such as an electrode for electrophysiological recording is coated with quantum dots. This greatly aids the ability to observe the glass pipette, particular in tissue as the quantum dots provide an excellent performance under two-photon illumination used to visualize objects at depths of hundreds of microns.

Abstract: The present invention provides a system and method of directing, focusing, or concentrating electrical charges within a defined electric field so that these charges can be used to exert forces on cells and tissues in vivo and/or cell cultures in vitro. The present invention reduces and/or eliminates the damage at a target site that would normally be caused by an electrode that acts as a current source or sink to accomplish the same task.

Abstract: An electroporation apparatus comprising an elongated hollow member in order to provide a uniform electric field during electroporation, wherein specifically, electroporation is carried out by applying electric pulses through a couple of electrodes from both end parts of the elongated hollow member, after the hollow member is charged with fluid specimen including cells and material which would be injected into the cells.

Abstract: Provided herein are improved multi-way cell sorter systems and methods. For example, provided are systems and methods for the collection of cells that are sorted in multiple directions. The systems and methods allow for the construction of a multi-way sorter (e.g., a ten-way sorter in the space that currently only allows four-way sorting). In addition the device may actively sense the arrival of drops (with cells of interest) at a sample tube, and trigger an alarm when the drops' arrivals deviate from an expected pattern.

Abstract: A biosensor chip with nano-structures. The biosensor chip includes a RF biosensor, comprising an isolated substrate; a ground plane; a filtering circuit; at least one cell detection area with nano-structures and a protection layer. The RF biosensor can detect the existence of the cancer cells, high frequency biological effects and the cells relationship between transfers by noninvasive method. The RF biosensor according to the invention can provide high accuracy and sensitivity in cancer cells detection.

Abstract: An electroporation apparatus comprising an elongated hollow member in order to provide a uniform electric field during electroporation, wherein specifically, electroporation is carried out by applying electric pulses through a couple of electrodes from both end parts of the elongated hollow member, after the hollow member is charged with fluid specimen including cells and material which would be injected into the cells.

Abstract: The present invention includes devices and methods for transfecting a cell or cell population and dynamic monitoring of cellular events. A variety of microelectronic devices are provide that incorporate functions such as electroporation, modulation of a transmembrane potential and dynamic monitoring of cellular functions and mechanisms.

Abstract: A system and method are described for electroporating a sample that utilizes one or more sets of electrodes that are spaced apart in order to hold a surface tension constrained sample between the electrodes. The first electrode is connected to the lower body of the system while the second electrode is connected to the upper body. Both electrodes are connected to a pulse generator. Each electrode has a sample contact surface such that the first electrode and the second electrode may be positioned to hold a surface tension constrained sample between the two sample contact surfaces and the sample may receive a selected electric pulse.

Abstract: A pulse generation system for applying electric pulses across a load includes a first plurality of energy storage modules connected in series on a positive chain and configured to apply a positive potential to the load and a second plurality of energy storage modules connected in series on a negative chain and configured to apply a negative potential to the load. Each energy storage module of the positive chain and the negative chain includes a rectifier and a storage element, and at least one control element.

Abstract: A testing device uses a selectively deformable substrate to capture and retain spherical beads for genetic experimentation. A method of fabricating the device is described in which a silicon substrate can be coated with a photosensitive, bio-compatible polymer for photolithographic patterning using a single mask exposure. The polymer is patterned with a matrix of wells, each well capable of expansion to accept placement of a bead in the well, and contraction to secure the bead in the well. The polymer can exhibit piezoelectric properties that cause it to respond mechanically to a selected electrical excitation.

Abstract: A mechanism is provided for utilizing a nanodevice to distinguish molecules with different structure. The molecules translocate through or across a nanochannel filled with a electrolyte solution. An electrical signal through the nanochannel is measured for every translocation event. Inner surfaces of the nanochannel include a functional layer, which is a coating to functionalize the nanochannel, in which the functional layer is configured to interact with predetermined ones of the molecules during translocation events. It is determined that a combination of at least two different molecules is formed based on predetermined ones of the molecules interacting with the functional layer to change the electrical signal and/or change a translocation time for the translocation event.

Abstract: A system and method is provided for non-invasively measuring changes in a specimen suspected of containing one or more microbes, by monitoring changes in the dielectric constant of the specimen caused by metabolic processes of such microbes.

Abstract: Systems and methods for manipulating molecular material are provided. In one aspect, for example, a method for manipulating molecular material may include positioning an uncharged needle structure in electrical proximity with a charged molecular material at a first locus in a liquid environment, charging the needle structure such that at least a portion of the charged molecular material becomes associated with the needle structure, moving the needle structure and the first locus relative to one another, and discharging the needle structure to disassociate the charged molecular material at a second locus.

Abstract: Methods for creating a transient nanoscale opening in a cell membrane and methods for transporting a desired species through the nanoscale opening are provided. A nano-sized needle-like tip can be used to mechanically slice the cell membrane to create a transient, localized nanoscale slit. The nanoscale slit may be used for transferring exogenous molecules into a living cell.

Abstract: Disclosed is an analysis method comprising the steps of: (a) reacting a substance to be analyzed with at least a specific partner which exhibits a selective interaction with the substance, converting a soluble substance to an insoluble substance by an insolubilization reaction, in correlation with the amount of the substance to be analyzed contained in a sample, and depositing the insoluble substance on a sensing part, and (b) electrically analyzing the insoluble substance deposited on the sensing part, wherein at least one of steps (a) and (b) is carried out under flow conditions.

Abstract: Systems, devices, and methods for delivering a biological material into a cell are provided. In one example, a lance device for introducing biological material into a cell and configured for use in a nanoinjection system including a microscope is provided. Such a device can include a lance having a tip region and a shaft region, wherein the lance is structurally configured to allow entry and movement of the tip region into the cell along an elongate axis of the tip region and along a focal plane of the microscope. In another example, the lance can be configured to allow substantially horizontal entry and movement of the tip region into the cell.

Abstract: Devices, systems and methods for increasing fermentation rates of microbes via biostimulation are provided. Electrodes are preferably positioned along an interior or exterior of a tube-shaped component to administer electromagnetic/electric pulses to a solution comprising a microbe. Systems can advantageously be used in new biofuels production plants, or in existing biofuels production plants without the need for significant retrofits.

Abstract: Provided herein are improved multi-way cell sorter systems and methods. For example, provided are systems and methods for the collection of cells that are sorted in multiple directions. The systems and methods allow for the construction of a multi-way sorter (e.g., a ten-way sorter in the space that currently only allows four-way sorting). In addition the device may actively sense the arrival of drops (with cells of interest) at a sample tube, and trigger an alarm when the drops' arrivals deviate from an expected pattern.

Abstract: Systems, devices, and methods for delivering a biological material into an organelle of a cell are provided. In one aspect, for example, a method for introducing biological material into an organelle of a cell can include bringing into proximity outside of a cell a lance and a preselected biological material, charging the lance with a polarity and a charge sufficient to electrically associate the preselected biological material with a tip portion of the lance, and penetrating an outer portion of the cell with the lance and directing and inserting the lance into the cell but outside of the organelle. The method can further include discharging the lance to release at least a portion of the biological material, charging the lance with an opposite polarity and charge sufficient to electrophoretically drive at least a portion of the biological material into the organelle, and withdrawing the lance from the cell.

Abstract: The present invention relates to a cell fusion chamber in which two types of cells having different diameters are fused, the cell fusion chamber including: a cell fusion region in which cell fusion is carried out; a pair of electrodes formed by a conductor and disposed opposite to each other in the cell fusion region; and a partition wall having at least one fine pore; near the fine pore, a cell fusion device including a cell fusion container containing a cell fusion region; a pair of electrodes; a spacer; and an insulator disposed between the spacer and one of the electrodes and having at least one fine pore; and an electronic power supply which applies an alternating voltage and a voltage pulsed direct current to the electrodes, and a cell fusion method using the same.

Abstract: Systems, devices, and methods for delivering a biological material into an organelle of a cell are provided. In one aspect, for example, a method for introducing biological material into an organelle of a cell includes bringing into proximity a lance and a preselected biological material outside of a cell and charging the lance with a polarity and a charge sufficient to electrically associate the preselected biological material with a tip portion of the lance. The method also includes penetrating an outer portion of the cell with the lance and directing and inserting the lance into an organelle, discharging the lance to release at least a portion of the biological material into the organelle, and withdrawing the lance from the cell.

Abstract: The present invention relates to methods for measuring an amount of an analyte using an electrochemical assay in a conduit comprising a sensor, wherein said sensor comprises an electrode having a surface layer of immobilized antibody that binds said analyte, and a counter/reference electrode disposed within said conduit. A solution comprising a substrate for said enzyme and at least one air segment contacts the sensor to remove unbound analyte and labeled antibody from a region of the sensor. The disclosed invention is adaptable to the point-of-care clinical diagnostic field, including use in accident sites, emergency rooms, surgery, nursing homes, intensive care units, and non-medical environments.

Abstract: A real-time method employing a portable peptide-containing potentiometric biosensor, can directly detect and/or quantify bacterial spores. Two peptides for specific recognition of B. subtilis and B. anthracis Sterne may be immobilized by a polysiloxane monolayer immobilization (PMI) technique. The sensors translate the biological recognition event into a potential change by detecting, for example, B. subtilis spores in a concentration range of 0.08-7.3×104 CFU/ml. The sensing method exhibited highly selective recognition properties towards Bacillus subtilis spores over other kinds of spores. The selectivity coefficients of the sensors for other kinds of spores are in the range of 0-1.0×10?5. The biosensor method not only has the specificity to distinguish Bacillus subtilis spores in a mixture of B. subtilis and B. thuringiensis (thur.) Kurstaki spores, but also can discriminate between live and dead B. subtilis spores. Furthermore, the sensing method can distinguish a Bacillus subtilis 1A700 from other B.

Abstract: The invention provides an organism for expressing foreign DNA, the organism engineered to accept standard DNA carriers. The genome of the organism codes for intracytoplasmic membranes and features an interruption in at least one of the genes coding for restriction enzymes. Further provided is a system for producing biological materials comprising: selecting a vehicle to carry DNA which codes for the biological materials; determining sites on the vehicle's DNA sequence susceptible to restriction enzyme cleavage; choosing an organism to accept the vehicle based on that organism not acting upon at least one of said vehicle's sites; engineering said vehicle to contain said DNA; thereby creating a synthetic vector; and causing the synthetic vector to enter the organism so as cause expression of said DNA.

Abstract: An apparatus for performing magnetic electroporation is disclosed. A required electric field for electroporation is generated using a pulsed magnetic field through a closed magnetic yoke, such as a toroid, placed in a flow path of a fluid medium to be processed. The fluid medium flows through the orifice of the magnetic yoke, with the fluid medium flowing through and around the yoke. The required power to send a maximum flux through the magnetic yoke is less than the required power in a conventional apparatus for performing electroporation.

Abstract: A system and method are described for electroporating a sample that utilizes one or more sets of electrodes that are spaced apart in order to hold a surface tension constrained sample between the electrodes. The first electrode is connected to the lower body of the system while the second electrode is connected to the upper body. Both electrodes are connected to a pulse generator. Each electrode has a sample contact surface such that the first electrode and the second electrode may be positioned to hold a surface tension constrained sample between the two sample contact surfaces and the sample may receive a selected electric pulse.

Abstract: A liquid sample flow containing living cells is irradiated with measurement laser light and the photo data of at least either scattering light or fluorescence that is generated by each of the living cells in the liquid sample flow due to the irradiation with the measurement laser light is acquired. Based on the photo data thus acquired, it is determined whether each of the cells assignable to the respective photo data is an unnecessary living cell or a target living cell. Based on the determination results, a pulse voltage is then applied exclusively to the living cells having been determined as unnecessary living cells so that the unnecessary living cells are damaged and killed.

Abstract: The present invention relates to methods for measuring an amount of an analyte using an electrochemical assay in a conduit comprising a sensor, wherein said sensor comprises an electrode having a surface layer of immobilized antibody that binds said analyte, and a counter/reference electrode disposed within said conduit. A solution comprising a substrate for said enzyme and at least one air segment contacts the sensor to remove unbound analyte and labeled antibody from a region of the sensor. The disclosed invention is adaptable to the point-of-care clinical diagnostic field, including use in accident sites, emergency rooms, surgery, nursing homes, intensive care units, and non-medical environments.

Abstract: The invention relates to an apparatus for introducing a biological material, a method of introducing a biological material, and a magnetic support for introducing a biological material with the object of providing an apparatus for introducing a biological material, a method of introducing a biological material, and a magnetic support for introducing a biological material whereby a biological material can be efficiently introduced into a host. The invention comprises: one or more packing units in which a mixture solution containing a large number of magnetic supports carrying a biological material to be introduced into a host such as cells upon using, together with a large number of the hosts in a liquid is pooled; and an introduction treatment unit in which a magnetic force affecting the inside of the packing unit is controlled so as to move the magnetic supports relatively with respect to the host so that the biological material can be introduced into the host.

Abstract: A molecular delivery device including a plurality of nanowires (e.g., Si NWs) coated with an electrically conductive layer. Also disclosed are methods for delivering a molecule by nanowire-mediated electroporation.

Abstract: The invention relates to a method for subjecting adherent cells to at least one electric field, in which the electric field is generated by applying a voltage to at least two active electrodes 63, wherein at least three electrodes 63, 64 are provided, and wherein at least two electrodes 63, 64 are active electrodes 63 when the voltage is applied in order to generate a first electric field, and in which at least one second electric field is generated, wherein at least one of the two previously active electrodes 63 is a potential-free electrode 64 when the voltage is applied.

Abstract: A fluid containing cells and free genetic material is acoustically coupled to a propulsion surface of a diaphragm. A blast-receiving surface of the diaphragm is acoustically coupled to an explosion chamber in which an explosive material is disposed. An ignition system ignites the explosive material in the explosion chamber to create a blast wave. The diaphragm transfers momentum from the blast wave to the fluid containing cells and free genetic material sufficient to cause the cells to take up the free genetic material.

Abstract: Transfecting biology cells with nucleic acid molecules (DNA, siRNA) is an essential prerequisite in elucidating how genes function in complex cellular context and how their activities could be modulated for therapeutic intervention. Traditionally studies are carried out on a low throughput gene-by-gene scale, which has created a huge bottleneck in functional genomic study and drug discovery. Development of high-throughput cell transfection technology will permit functional analysis of massive number of genes and how their activities could be modulated by chemical or biological entities inside cells. This invention describes design, construction of device and apparatus for high throughput effective cell transfection. Procedures and protocols for using the device and apparatus are also described in the application. Novel methods of using the device in cell-based assays are also disclosed.