Abstract: The present invention relates to a new cell based assay for combined determination of antibody or ligand binding and function in the same vial.

Abstract: Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, coumarins, cyanines, bimanes, and difuloroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer.

Abstract: The invention relates to functional lipid constructs and their use in diagnostic and therapeutic applications, including serodiagnosis, where the functional moiety is carbohydrate, peptide, chemically reactive group, conjugator or fluorophore.

Abstract: Provided are methods for determining the presence or absence of donor specific antibodies in a biological sample. The methods include mixing a cellular sample from a donor with a biological sample from a recipient under conditions sufficient for recipient immune antibodies, if present, to bind to donor cell surface antigen (Ag) to form an immune antibody-Ag complex, contacting the mixture with beads comprising an antibody that specifically binds the immune antibody-Ag complex (e.g., the Ag or immune antibody) on a surface thereof, adding under lysis conditions a detectably-labeled antibody that specifically binds the immune antibody-Ag complex bound to the beads, and detecting the presence or absence of the detectably-labeled antibody bound to the immune antibody-Ag complex to determine the presence or absence of donor specific antibodies in the biological sample from the recipient. Systems and kits for practicing the subject methods are also provided.

Abstract: The present invention provides a three-dimensional bioprinter for fabricating cellular constructs such as tissues and organs using electromagnetic radiation (EMR) at or above 405 nm. The bioprinter includes a material deposition device comprising a cartridge for receiving and holding a composition which contains biomaterial that cures after exposure to EMR. The bioprinter also includes an EMR module that emits EMR at a wavelength of about 405 nm or higher. Also provided is a bioprinter cartridge which contains cells and a material curable at a wavelength of about 405 nm or greater. The cells are present in a chamber and are extruded through an orifice to form the cellular construct.

Abstract: Methods of enhancing membrane permeabilization in a cell are provided. A method includes disposing the cell between a first electrode and a second electrode and applying a plurality of electrical pulses between the first electrode and the second electrode. In the method, the plurality of electrical pulses include at least two trains of pulses separated by an interval greater than about 10 s. Further, the amplitude of the electrical pulses is selected to be greater than about 0.2 kV/cm.

Abstract: Provided are methods for determining the presence or absence of donor specific antibodies in a biological sample. The methods include mixing a cellular sample from a donor with a biological sample from a recipient under conditions sufficient for recipient immune antibodies, if present, to bind to donor cell surface antigen (Ag) to form an immune antibody-Ag complex, contacting the mixture with beads comprising an antibody that specifically binds the immune antibody-Ag complex (e.g., the Ag or immune antibody) on a surface thereof, adding under lysis conditions a detectably-labeled antibody that specifically binds the immune antibody-Ag complex bound to the beads, and detecting the presence or absence of the detectably-labeled antibody bound to the immune antibody-Ag complex to determine the presence or absence of donor specific antibodies in the biological sample from the recipient. Systems and kits for practicing the subject methods are also provided.

Abstract: Provided is a primary cell isolating apparatus that includes, sequentially adjacent, a slicing space, a working space, a picking space, and a sliding device mounted through the above spaces. The slicing space has a slicing device. The working space has a first gate, a heater, a rotating holder, a centrifuge, an open-close cap device, a tube rack, and a liquid transferring device. The first gate is adjacent to the slicing space. The heater is proximal to the first gate, and is sequentially adjacent to the rotating holder and the centrifuge. The open-close cap device is proximal to the first gate and is opposite the heater, and is sequentially adjacent to the tube rack and the liquid transferring device. The picking space has a second gate adjacent to the working space. Also provided is a method of using the primary cell isolating apparatus as abovementioned for saving manpower.

Abstract: The invention relates to methods for effecting qualitative and quantitative changes in the functional moieties expressed at the surface of cells and multi-cellular structures, and functional lipid constructs for use in such methods. In particular, the invention relates to functional lipid constructs and their use in diagnostic and therapeutic applications, including serodiagnosis, where the functional moiety is a carbohydrate, peptide, chemically reactive group, conjugator or fluorophore.

Abstract: Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, coumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer.

Abstract: A scanning electron microscope suitable for imaging samples in a non-vacuum environment, the scanning electron microscope including an electron source located within an enclosure maintained under vacuum, an electron permeable membrane disposed at an opening of the enclosure separating an environment within the enclosure which is maintained under vacuum and an environment outside the enclosure which is not maintained under vacuum, the electron permeable membrane not being electrically grounded and at least one non-grounded electrode operative as an electron detector.

Abstract: Cells that are in the process division are vulnerable to damage by AC electric fields that have specific frequency and field strength characteristics. The selective destruction of rapidly dividing cells can therefore be accomplished by imposing an AC electric field in a target region for extended periods of time at particular frequencies with particular filed strengths. Some of the cells that divide while the field is applied will be damaged, but the cells that do not divide will not be harmed. This selectively damages rapidly dividing cells like bacteria, but does not harm normal cells that are not dividing. Improved results can be obtained when the field is sequentially imposed in different directions.

Abstract: Improved methods and systems for processing of solid tissue are described. The method may be performed manually or automatically. The system may have modules such as (i) a grossing module where a fresh tissue is sliced to prepare a tissue specimen, (ii) a hardening module that hardens the tissue specimen, (iii) an impregnating module that impregnates the tissue specimen that was hardened, and (iv) an embedding module that embeds a tissue specimen that was hardened and impregnated. Fresh (i.e., not fixed or frozen) tissue, which was excised to diagnose disease or to assess surgical treatment, is grossed to about 0.6 mm. Preferably, the hardening of fresh tissue is initiated, but not completed, during grossing by contact with a chemical admixture. Preferably, dry ice, a thermoelectric device, or a gas condenser cools a metal mold containing the embedded specimen.

Abstract: The present invention provides a method and system for using eye-safe infrared energy from a Class I laser to manipulate cells in culture. The laser energy produces one or more phase boundary propulsion events, which generate hydrodynamic forces sufficient to manipulate cells at the focal point.

Abstract: Apparatus, compositions, methods, and articles of manufacture are disclosed relating to the design and production of biological components and/or their incorporation in devices and systems, including biohybrid photosensitive devices and systems. In some embodiments, biological components include light antenna structures that collect light and emit Stokes-shifted light to a photoactive non-biological component. In some embodiments, the characteristics of biological components are engineered via force-adaptation of an organism or adaptive system. In some embodiments, biological components are modified by removing reaction centers or other structure not contributing to desired performance.

Abstract: The present invention relates to systems for releasing genetic materials from a solid medium. The present invention also relates to methods for releasing genetic materials from a solid medium. The present invention further relates to methods for isolating genetic material from a biological sample.

Abstract: The present invention stems from the finding that the extracellular domain of CD31 proteins present on blood leukocytes is shed and released in the circulation as a soluble form of CD31. A method for detecting shed CD31 is further disclosed. The invention therefore relates to a method for detecting a shed ectodomain of a transmembrane protein such as CD31 and to the use of such a method as a diagnostic tool. The invention further provides methods for determining whether a candidate protein is part of a molecular complex.

Abstract: The present invention relates to signaling mechanisms that transduce magnetic inputs into physiological cellular outputs. More particularly, the present invention relates to systems and methods for non-invasively controlling cellular signaling functions and behaviors by harnessing receptor-mediated and intracellular molecular-mediated signal transduction using nanomagnetic cellular switches.

Abstract: Method for the selection or the processing of first particles sensitive to the application of an external stimulus including the step of producing, through the application of the external stimulus, the permeabilization of at least a selected first particle, consisting in the organization of the first particles through a first force field, to generate a second force field substantially placed in proximity of at least a selected first particle to be permeabilized.

Abstract: The invention generally relates to methods of using compositions that include sets of magnetic particles, members of each set being conjugated to an antibody specific for a pathogen, and magnets to isolate a pathogen from a body fluid sample.

Abstract: The invention aims at providing an adsorbent for bacterial toxins, a method for removal of such toxins by adsorption, and an adsorber packed with said adsorbent. Provided are an adsorbent for bacterial toxins, which comprises a water-insoluble porous material having a mode of pore radius of 20 angstroms to 1,000 angstroms, a method for removal of bacterial toxins using said adsorbent, and an adsorber packed with said adsorbent.

Abstract: To provide a system by which evaluation of circumstances of contamination by microparticles having nucleic acid can be performed rapidly and accurately. The theme is achieved by a system for measuring microparticles that includes: (1) a microparticle adhesion step of adhering the microparticles having nucleic acid to a microparticle adhesion member; (2) a membrane breakage step of breaking membranes of the adhered microparticles by electrical discharge; (3) an electrophoresis step of electrophoresing the microparticles in a thickness direction of a gel to make the nucleic acid in the microparticles migrate from a negative electrode side toward a positive electrode side and adhere the nucleic acid on a surface of a nucleic acid detection member; and (4) a nucleic acid measurement step of fluorescently staining the surface of the nucleic acid detection member to measure a concentration of the nucleic acid.

Abstract: A method of delivering exogenous molecules, comprising: providing a plurality of cells having a cell membrane; adding a plurality of exogenous molecules to the cells; exposing the cells to a defocused infrared (IR) light to permeabilize the cell membrane of the cells; and delivering the exogenous molecules to the cells through the permeablized cell membrane, wherein an intensity of the IR light at the optical focus is at least greater than or equal to an order of 104 W/cm2.

Abstract: The present invention relates to a device comprising an organic field effect transistor (OFET) with charge injecting contacts containing a semiconductor layer formed by a perylene derivative, to uses of said device as a medical sensor and/or as a medical cell stimulator and to methods of stimulating and/or monitoring biological cellular activity by using said device.

Abstract: The present invention disposes a membrane between two electrical conductive walls having a height at least as great as the thickness of the membrane. The conductive walls are fabricated on an electrically insolative chip base. The chip base has one or more through hole between the electrically conducting walls. The chip is placed inside a container having a well below the through hole of the electrically insolative base. At least one passageway extends from the well to the periphery of the container. This invention probes changes of the membrane as an in-plane electric field is applied between the conductive walls. The well may include various compounds while-other compounds can be placed in contact with the top of the membrane. The passageways are used to introduce substances into and out of the well.

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: 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: Described herein are bioprinters comprising: one or more printer heads, wherein a printer head comprises a means for receiving and holding at least one cartridge, and wherein said cartridge comprises contents selected from one or more of: bio-ink, and support material; a UV light module for optionally exposing the contents of at least one cartridge to UV light; a means for calibrating the position of at least one cartridge; and a means for dispensing the contents of at least one cartridge. Also described herein are methods of using and bioprinting cartridges for such bioprinters.

Abstract: Provided herein are methods of inducing psychosis in animals using light-responsive opsins and methods of identifying or screening compounds that may be useful in treating psychosis.

Abstract: The invention relates to methods for effecting qualitative and quantitative changes in the functional moieties expressed at the surface of cells and multi-cellular structures, and functional lipid constructs for use in such methods. In particular, the invention relates to functional lipid constructs and their use in diagnostic and therapeutic applications, including serodiagnosis, where the functional moiety is a carbohydrate, peptide, chemically reactive group, conjugator or fluorophore.

Abstract: The present invention provides a sonoporation-based method that can be universally applied for delivery of compounds into Gram positive bacteria. Gram positive bacteria which can be transformed by sonoporation include, for example, Bacillus, Streptococcus, Acetobacterium, and Clostridium. Compounds which can be delivered into Gram positive bacteria via sonoporation include nucleic acids (DNA or RNA), proteins, lipids, carbohydrates, viruses, small organic and inorganic molecules, and nano-particles.

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 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: Various systems and methods are implemented for controlling stimulus of a cell. One such method is implemented for optical stimulation of a cell expressing a NpHR ion pump. The method includes the step of providing a sequence of stimuli to the cell. Each stimulus increases the probability of depolarization events occurring in the cell. Light is provided to the cell to activate the expressed NpHR ion pump, thereby decreasing the probability of depolarization events occurring in the cell.

Abstract: Provided herein are compositions comprising light-activated chimeric proteins expressed on plasma membranes and methods of using the same to selectively depolarize excitatory or inhibitory neurons.

Abstract: The invention concerns a device and a method for concentrating pathogenic germs potentiaily present in blood products or derivatives and for detecting said germs comprising the following steps: (a) subjecting a sample of said blood product to a blood cell aggregating treatment, (b) eliminating the aggregates formed at step (a) by passing the treated sample over a first filter allowing through the contaminating germs but not the cell aggregates, (c) selectively lyzing the residual cells of the filtrate obtained at step (b), (d) recuperating the contaminating germs by passing the lysate of step (c) over a second filter to detect the contaminating germs possibly trapped.

Abstract: The invention is a device including array of aciive regions for use in reacting one or more species in at least two of the active regions in a sequential process, e.g., sequential reactions. The device has a transparent substrate member, which has a surface region and a silane material overlying the surface region. A first active region overlies a first portion of the silane material. The first region has a first dimension of less than 1 micron in size and has first molecules capable of binding to the first portion of the silane material. A second active region overlies a second portion of the silane material. The second region has a second dimension of less than 1 micron in size, second molecules capable of binding to the second portion of the active region, and a spatial distance separates the first active region and the second active region.

Abstract: Means, compositions, and uses for triggering exocytosis of lysosomes in living cells. During exocytosis, lysosomes travel to the plasma membrane of the cell and dump their contents outside of the cells, thus removing accumulations of harmful, reactive metabolic by-products, such as lipofuscin. Consequently, cells function better, thus improving their vitality and the vitality of people, animals, and cell cultures. Degenerative diseases can be prevented or reversed. Embodied methods include electrical pulses, sonic vibrations, mechanical pressure, and mixtures of substances, which may include drugs, proteins, antibodies, or liposomes, which can be combined, injected, or administered transdermally or orally. Other embodiments are described and shown.

Abstract: A method for facilitating a delivery of a molecule into an interior space of a cell includes the steps of introducing a molecule into a biological structure comprising a cell and applying a substantially continuous low-level electric field, in the form of non-thermal plasma (ionized gas) generated by a direct current voltage applied to an electrode, to the molecule and biological structure. The field is applied for a duration sufficient to effect a change in porosity the cell of the biological structure sufficient to facilitate an entry of a desired molecule into an interior thereof.

Abstract: The invention concerns a recombinant vector characterized in that it comprises a polynucleotide comprising a central initiation cis-active region (cPPT) and a termination cis-active region (CTS), the regions being of retroviral or retroviral-like origin, and the vector further comprising a predetermined nucleotide sequence (transgene or nucleotide sequence of interest) and retrotranscription regulating, expressing, and packaging signals of retroviral or retroviral-like origin.

Abstract: A microfluidic cartridge for isolating biological molecules having a capture chamber containing functionalized solid supports maintained in a fluidized state provides reduced pressure drops and bubble formation during microfluidic extraction. The cartridge may include an electric field lysis chamber and/or a chemical lysis chamber. The electric-field lysis chamber may comprise an electrically insulating structure arranged between two opposing planar electrodes.

Abstract: Disclosed is a method for selective electrofusion of at least two fusion partners having cell-like membranes and cellular or subcellular dimensions, comprising the following steps: A) the fusion partners are brought into contact with each other and B) an electrical field of a strength sufficient to obtain fusion and highly focused on the fusion partners is applied. The fusion partners are independently selected from the group consisting of a single cell, a liposome, a proteoliposome, a synthetic vesicle, an egg cell, an enucleated egg cell, a sperm cell at any development stage and a plant protoplast.

Abstract: Disclosed are polynucleotides and methods for expressing light activated proteins in animal cells and altering an action potential of the cells by optical stimulation. The disclosure also provides animal cells and non-human animals comprising cells expressing the light-activated proteins.

Abstract: A method of optoperforation of the membrane of a cell by application of laser pulses characterized by focusing the pulsed laser beam onto the cell membrane to be perforated, applying a series of laser pulses of predetermined pulse energy, measuring the oscillation time of the bubbles formed in the laser focus from the change in laser intensity of a test laser beam transmitted through the laser focus and caused by the bubbles in the laser focus, and increasing the pulse energy to a level at which the oscillation time of the bubbles attains a predetermined value.

Abstract: Methods and devices for causing uptake of materials by cells, temporary using local chemical environment modification. The modification may be caused chemically by reducing pH. The uptake method is passive and does not require bioactivity of the cells.

Abstract: A cancer cell separating apparatus includes: a flow channel including an antibody fixation area having antibodies which bind specifically to cancer cells fixed thereon, wherein the cancer cells and non-cancer cells are separated using a difference in velocity of movement between the cancer cells and the non-cancer cells in cell slurry introduced into the flow channel.

Abstract: Disclosed is a method for parallel delivery of agents to and/or into a cell structure, wherein at least two electrolyte-filled tubes are provided together with a counter electrode, the tubes being connected to a voltage or current generator, said agents being introduced into the electrolyte solution contained in the tubes, which are placed close to the cell structure, whereupon the agents are transported through the tubes to said cell structure and into the said structure through pores which have been formed by application of an electric field focused on the cell structure, resulting in electroporation of the cell structure. Also different applications of the method is disclosed, e.g. use of the method in order to transfer cell-impermeant solutes, such as drugs or genes, into the cell structure or out of the cell structure.

Abstract: A micromachined patch-clamp apparatus is disclosed for holding one or more cells and providing electrical, chemical, or mechanical stimulation to the cells during analysis with the patch-clamp technique for studying ion channels in cell membranes. The apparatus formed on a silicon substrate utilizes a lower chamber formed from silicon nitride using surface micromachining and an upper chamber formed from a molded polymer material. An opening in a common wall between the chambers is used to trap and hold a cell for analysis using the patch-clamp technique with sensing electrodes on each side of the cell. Some embodiments of the present invention utilize one or more electrostatic actuators formed on the substrate to provide mechanical stimulation to the cell being analyzed, or to provide information about mechanical movement of the cell in response to electrical or chemical stimulation.

Abstract: The present application includes systems and methods for identifying a compound capable of interacting with a G-Protein Coupled Receptor (GPCR) or Receptor Tyrosine Kinase (RTK) including providing a device capable of measuring cell-substrate impedance operably connected to an impedance analyzer, adding test cells expressing a GPCR or a RTK to wells of the device, measuring first impedances of the wells and optionally determining first cell indices from the first impedances, adding a compound to at least one well containing test cells to form at least one compound well and adding a vehicle control to at least another well containing test cells to form at least one control well, measuring second impedances of the compound well and the control well and optionally determining second cell indices from the second impedances, determining the change in the impedance or cell index for the compound well and the one control well, comparing the change in impedance or cell index between the compound well and the control

Abstract: An extracellular potential measuring device includes a plate portion having a first surface and a second surface opposite to the first surface, and an electrode provided on the second surface of the plate portion. In the plate portion, a pocket having an opening which opens to the first surface is formed, and a through-hole communicating to the second surface from the pocket. The through-hole communicates from a position which is closer to the opening than a deepest point of the first pocket. The electrode is provided around of the opening of the through-hole. In this device, even if a cell to be examined does not reach the deepest point of the pocket, a cell membrane of the cell can tightly attaches onto the through-hole securely without a clearance. Hence, culture solution inside the through-hole is isolated from culture solution over an upper surface of the plate portion, thereby allowing electrochemical changes caused by activities of the cell to be detected efficiently with a detector electrode.