Abstract: An apparatus for thermally cycling samples of a biological material including a thermal block assembly including a plurality of sample holders for receiving samples of biological material; a heat sink thermally coupled to the thermal block assembly, the heat sink transferring heat away from the thermal block assembly to ambient air in contact with the heat sink; a first heat source thermally coupled to the thermal block assembly to provide heat to the thermal block assembly; and a second heat source thermally coupled to the first heat source and configured to provide heat to a portion of the first heat source. The arrangement of the heat sink, first heat source and second heat source can provide substantial temperature uniformity among the plurality of sample holders. The invention also includes a method for thermally cycling samples of biological material.

Abstract: The sample temperature regulator is provided with a heating block (3) having a sample container holder (6) and a temperature-controllable heater (7) and with a cooling block (4) having a cooling mechanism (11). These two blocks are combined with each other through a connecting plate (15) made of a material having a thermal conductivity lower than those of these blocks. This constitution can reduce heat transfer between the heating block and the cooling block and allows them to have wide temperature regulating ranges, as well as increased heating capacity and cooling capacity, respectively. Further, this constitution makes the structure of the temperature regulator simple and compact, so that the regulator has increased durability and can be offered at a low price.

Abstract: A method and a device are used for carrying out measurements on cells located in a liquid environment. Each cell is positioned with an underside of its membrane on a surface having a channel running through it. A negative pressure is established to aspirate the cells. Each cell is electrically scanned via at least one electrode which is spaced apart from the cell. The negative pressure is preferably established in a pulse-like manner to rupture the membrane in such a way that the cell interior enclosed by the membrane is connected to the channel.

Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide polymerization reaction. The devices comprise a substrate microfabricated to define a sample inlet port and a mesoscale flow system, which extends from the inlet port. The mesoscale flow system includes a polynucleotide polymerization reaction chamber in fluid communication with the inlet port which is provided with reagents required for polymerization and amplification of a preselected polynucleotide. In one embodiment the devices may be utilized to implement a polymerase chain reaction (PCR) in the reaction chamber (PCR chamber).

Abstract: The invention provides apparatus and methods for determining the nucleotide sequence of target nucleic acids using hybridization to arrays of oligonucleotides. The invention further provides apparatus and methods for identifying the amino acid sequence of peptides that bind to biologically active macromolecules, by specifically binding biologically active macromolecules to arrays of peptides or peptide mimetics.

Abstract: The present invention relates to a method of manufacturing a kit for isolating and purifying nucleic acids, or various biological materials, a kit manufactured by the method, and an apparatus using the kit. The method of manufacturing a kit for isolating or purifying nucleic acids or biological materials from biological samples using solid materials comprises the steps of; fabricating a container having a plurality of chambers and/or column which is configured to contain the solid materials, buffers and/or enzymes suitable for isolation of the nucleic acids or biological materials; fabricating a cover including a protruded portion with a bore formed therethrough; filling each of the chambers or column with the solid materials, buffers and/or enzymes for isolation and purification of the biological materials or nucleic acids; sealing the container with a predetermined sealing material; and packaging the cover and the container, one by one, with a separate case.

Abstract: A sleeve-type silicon polymerase chain reaction (PCR) chamber or thermocycler having improved thermal performance. The silicon sleeve reaction chamber is improved in thermal performance by etched features therein that reduce thermal mass and increase the surface area of the sleeve for cooling. This improved thermal performance of the thermocycler enables an increase in speed and efficiency of the reaction chamber. The improvement is accomplished by providing grooves in the faces of the sleeve and a series of grooves on the interior surfaces that connect with grooves on the faces of the sleeve. The grooves can be anisotropically etched in the silicon sleeve simultaneously with formation of the chamber.

Abstract: The invention relates to a device and a method for the detection, especially on line detection, of an amplification of a DNA and/or RNA sequence in a sample. The amplification of the DNA and/or RNA sequence in the sample is evaluated on the basis of scattered-light signal of the sample.

Abstract: The microfabricated cell injector having an injection wall and a cell injection needle projecting from the wall for piercing cells suspended in a fluid. The needle is held within a housing defined by the internal surfaces of the microfabricated cell injector. The housing has an inlet for suspended cells to enter and an outlet for cells to exit via the cell injection needle. A cell propulsion device is provided for impelling cells towards the needle such that, in use, cells suspended in the fluid are impelled towards the injection wall by the injection needle.

Abstract: An organism cell auto-handling apparatus includes a platform, an organelle observation microscope unit, a piping device and a system controller. An organism cell auto-handling method using the aforesaid apparatus includes the steps of putting an organism cell sample on the platform, then using the organelle observation microscope unit to position a specific organelle of said organism cell sample and produce a corresponding coordinate data to the system controller, and then processing an organelle draw/injection action to the specific organelle by a micro needle of the piping device that is controlled by the system controller.

Abstract: An apparatus for injecting a substance into a cell includes a cell input part to input the cell, a cell output part to output the cell, a flow path that connects the cell input part and the cell output part, wherein the cell flows in the flow path from the cell input part toward the cell output part, a trapping part that is arranged in the flow path and traps the cell that flows in the flow path, and an inserting part that allows to pass a needle that injects the substance into the cell that is trapped at the trapping part. The cell injected with the substance flows in the flow path toward the cell output part and the cell can be retrieved from the cell output part.

Abstract: Apparatus for conducting electrophysiological measurements on cells wherein a measuring head is provided with at least one electrode in a common support for impaling the cells.

Abstract: Systems and methods are described for parallel macromolecular delivery and biochemical/electrochemical interface to whole cells employing carbon nanostructures including nanofibers and nanotubes. A method includes providing a first material on at least a first portion of a first surface of a first tip of a first elongated carbon nanostructure; providing a second material on at least a second portion of a second surface of a second tip of a second elongated carbon nanostructure, the second elongated carbon nanostructure coupled to, and substantially parallel to, the first elongated carbon nanostructure; and penetrating a boundary of a biological sample with at least one member selected from the group consisting of the first tip and the second tip.

Abstract: The present invention relates to the use of porous silicon in the delivery of substances into cells. The porous silicon can be formed into micropiercers, microneedles and biolistic bullets for peenetration of the cell. The control of the pore size and porosity of the porous silicon allows tuning of the bioactivity of the porous silicon. The porous silicon is also resorbable and is therefore resorbed from the cells without leaving any particles or being seen as a foreign body. The present invention also relates to the methods of manufacturing the porous silicon micropiercers, microneedles, microelectrodes, biolistic bullets, and precipitation of calcium phosphate on a bioactive substrate, and their advantages over known methods of delivering materials into cells.

Abstract: Method and apparatus for accelerating micro particles for use in delivering DNA or a solid drug in which a shockwave is generated by applying a short pulse energy to a surface of a metal foil to be absorbed and cause vaporization and plasmatization of the metal foil. A jet is generated by a sudden expansion of metal gas and thereby the shockwave is generated on a surface of an opposite side of the metal foil on which the micro particles are arranged.

Abstract: A device for the delivery of treatment material to radiopharmaceutical labeled diseased or malfunctioning candidate cells within a human body an a method for using the device. The method includes the labeling of target cells in a body with a radionuclide, the identification in situ of the candidate cells using a nuclear probe sensitive to the presence of the radionuclide label and delivery of the treatment compound to the cell. while the probe is at the site of the labeled cells. More particularly, the invention relates to in situ gene therapy using a beta or gamma probe to locate labeled cells, also referred to as candidate cells, and the delivery of corrective genes, cells or biological vectors to the candidate cells identified by the probe while the probe is positioned adjacent to the labeled and located cells. The device is part of a system which provides a quantitative measure of the amount of radiation emanating from the labeled tissue targeted by the probe.

Abstract: A portable polymerase chain reaction DNA amplification and detection system includes one or more chamber modules. Each module supports a duplex assay of a biological sample. Each module has two parallel interrogation ports with a linear optical system. The system is capable of being handheld.

Abstract: The rate of nucleic acid strand exchange can be greatly enhanced if one of the strands of a double-stranded nucleic acid oligomer has a single-stranded extension, or “toehold,” to which a complementary, single-stranded, nucleic acid oligomer can bind. Toehold-facilitated strand exchange makes possible the controlled addition and removal of one nucleic acid strand from a second, complementary strand. Oligomers are designed and used to carry out controlled, repetitive nucleic acid structural transitions mediated by hybridization and toehold-facilitated strand exchange reactions, which in turn control the operation of a nanomachine or a 2-state molecular switch.

Abstract: A cell transfection apparatus and methods for making and using the cell transfection apparatus are described. The cell transfection apparatus has a surface on which there is printed at different locations one or more foreign biomolecules (e.g., DNA, RNA, oligonucleotides, nucleotides). The foreign biomolecules can be printed at the same time. The surface is then covered with a transfection reagent which is incubated and removed from the surface before cells in a cell growth media are placed on the surface. The surface is configured such that the cells which become transfected with one or more foreign biomolecules are segregated from the cells which fail to become transfected with one or more foreign biomolecules. There are disclosed two embodiments of the cell transfection apparatus.

Abstract: The present invention provides a cell-manipulating apparatus and method, wherein a gene or a gene expression-related substance is immobilized onto a needle-shaped body such as a carbon nanotube, and the needle-shaped body is inserted into and held in a cell. The present invention allows temporal dynamic changes appearing in the cell to be intimately observed in real time from gene introduction to gene expression.

Abstract: An apparatus for thermally cycling samples of a biological material including a thermal block assembly including a plurality of sample holders for receiving samples of biological material; a heat sink thermally coupled to the thermal block assembly, the heat sink transferring heat away from the thermal block assembly to ambient air in contact with the heat sink; a first heat source thermally coupled to the thermal block assembly to provide heat to the thermal block assembly; and a second heat source thermally coupled to the first heat source and configured to provide heat to a portion of the first heat source. The arrangement of the heat sink, first heat source and second heat source can provide substantial temperature uniformity among the plurality of sample holders. The invention also includes a method for thermally cycling samples of biological material.

Abstract: A cell transfection apparatus and methods for making and using the cell transfection apparatus are described. The cell transfection apparatus has a surface on which there is printed at different locations one or more foreign biomolecules (e.g., DNA, RNA, oligonucleotides, nucleotides). The foreign biomolecules can be printed at the same time. The surface is then covered with a transfection reagent which is incubated and removed from the surface before cells in a cell growth media are placed on the surface. The surface is configured such that the cells which become transfected with one or more foreign biomolecules are segregated from the cells which fail to become transfected with one or more foreign biomolecules. There are disclosed two embodiments of the cell transfection apparatus.

Abstract: An apparatus and method are disclosed for in vitro transformation of living cells. The apparatus, which is formed as a microelectromechanical device by surface micromachining, can be used to temporarily disrupt the cell walls or membrane of host cells one at a time so that a particular substance (e.g. a molecular tag, nucleic acid, bacteria, virus etc.) can be introduced into the cell. Disruption of the integrity of the host cells (i.e. poration) can be performed mechanically or electrically, or by both while the host cells are contained within a flow channel. Mechanical poration is possible using a moveable member which has a pointed or serrated edge and which is driven by an electrostatic actuator to abrade, impact or penetrate the host cell. Electroporation is produced by generating a relatively high electric field across the host cell when the host cell is located in the flow channel between a pair of electrodes having a voltage applied therebetween.

Abstract: A technique for controlling membrane denaturation reactions other than physical shear force was developed. For example, the present invention provides, a method for causing membrane disruption at a specific site by reacting a stimulus such as light with a compound that is activated by the stimulus, where the reaction occurs on a membrane such as a biomembrane. It also provides a membrane structure such as cells in which a specific site has been disrupted, which are obtained by the present method. Introduction of substances such as genes also became possible by using this membrane structure. Further provided is a membrane-destroying member for disrupting a membrane at a specific site. Thus, the present invention enabled, for example, easy membrane penetration using components constituting microelectrodes, micromanipulators, and microinjectors, which were conventionally hardly usable in penetrating cell membranes.

Abstract: The invention relates to a process for a simplified and rapid preparation of sterile culture media using microwave ovens. The sterile media of the invention are usable for the selection and identification of microorganisms transformed by viral or plasmid DNA.

Abstract: A method of delivery of reactive substances that are attached to magnetizable needle-like particles using a magneto-mechanical delivery device. The subject method and device can be utilized for the delivery of reactive or other substances, such as DNA via the penetration of a target body. Such penetration of a target or multiple targets can initiate the interaction between the material contained within the target site and the chemical substances delivered by the particles into the targets. In a preferred embodiment, the subject device is portable and does not require electrical power.

Abstract: An apparatus for microinjection of samples into amphibian oocytes, comprising a tray for holding a plurality of the amphibian oocytes, an injection needle for injecting a sample into the said amphibian oocytes, a driving means for moving a relative position between the said tray and the said injection needle and a controlling means for controlling the said movement by imputing a depth of the said injection needle for the said tray or the said amphibian oocytes in the injection of the sample, and injecting the sample into the said amphibian oocytes at the said depth. According to the present invention, the sample can be injected into the amphibian oocyte with constant depth.precisely and quality of oocyte or a positional site of needle injection can be recorded as the information.

Abstract: A cell transfection apparatus and methods for making and using the cell transfection apparatus are described. The cell transfection apparatus has a surface on which there is printed at different locations one or more foreign biomolecules (e.g., DNA, RNA, oligonucleotides, nucleotides). The foreign biomolecules can be printed at the same time. The surface is then covered with a transfection reagent which is incubated and removed from the surface before cells in a cell growth media are placed on the surface. The surface is configured such that the cells which become transfected with one or more foreign biomolecules are segregated from the cells which fail to become transfected with one or more foreign biomolecules. There are disclosed two embodiments of the cell transfection apparatus.

Abstract: The present invention provides a method and an improved apparatus for removing gas bubbles from a reaction chamber comprising a flexible layer removably affixed to a substrate layer having a multiplicity of oligonucleotide binding sites disposed thereon, in which biological reactions are performed. The invention specifically relates to methods and apparatus for removing gas bubbles from a reaction chamber wherein target molecules contained in a sample fluid are reacted with probe molecules immobilized on a substrate having an array of oligonucleotide binding sites. The arrays are covered with a flexible, gas permeable layer that permits mixing of the sample fluid on the biochip and removal of gas bubbles from the fluid by use of a means for facilitating diffusion of gas bubbles across the flexible, gas permeable layer.

Abstract: This invention provides a pattern exposure method which may be used for effectively preparing, for example, a DNA or peptide array with a lower cost and a device therefor. Specifically, the method is a method for pattern exposure comprising the step of exposing a photosensitive material on a solid-phase substrate by irradiating it with a light as a pattern, wherein the photosensitive material is selectively exposed with beams selectively emitted from multiple vertical cavity surface emitting laser sources aligned as an array.

Abstract: A cell transfection apparatus and methods for making and using the cell transfection apparatus are described. The cell transfection apparatus has a surface on which there is printed at different locations one or more foreign biomolecules (e.g., DNA, RNA, oligonucleotides, nucleotides). The foreign biomolecules can be printed at the same time. The surface is then covered with a transfection reagent which is incubated and removed from the surface before cells in a cell growth media are placed on the surface. The surface is configured such that the cells which become transfected with one or more foreign biomolecules are segregated from the cells which fail to become transfected with one or more foreign biomolecules. There are disclosed two embodiments of the cell transfection apparatus.

Abstract: Provided is a method for introducing a substance into a cell, which method comprises: (a) generating one or more bubbles of a gas in a liquid medium comprising the cell, the bubbles being capable of forming a hole in the surface of the cell when one or more bubbles interact with the cell; and (b) introducing the substance into the cell.

Abstract: A device for preparing an undifferentiated cell, the device comprises means for contacting a more committed cell with an agent that causes the more committed cell to retrodifferentiate into an undifferentiated cell.

Abstract: A perfusion chamber includes a porous oocyte support structure. A continuously sloped top surface and a receiving well in the support structure entrap the underside of the oocyte, thereby localizing the cell in a predetermined fixed position within the reach of dedicated voltage-clamp microelectrodes. A test solution is delivered continuously at the top of the chamber, above the oocyte, and withdrawn from the bottom of the chamber, below the oocyte. The porosity of the support material enables the continuous perfusion of test solution around the membrane of the oocyte, including its bottom portion that is held firmly in contact with the holding well. The geometry of the holding well is selected such as to ensure the automatic and precise placement of the oocyte by gravity and to optimize the pressure distribution over its membrane, thereby minimizing the probability of rupture or other damage to the cell.

Abstract: In a preferred embodiment, a polymerase chain reaction temperature control system, including: a first tank into which a multiwell sample carrier may be placed; apparatus to introduce first temperature controlled heat transfer medium into the first tank for a first predetermined length of time; and apparatus to subsequently introduce at least a second second temperature controlled heat transfer medium into the first tank for at least a second predetermined length of time.

Abstract: An apparatus and method for detecting the presence of at least two predetermined known materials in a test sample are disclosed. The apparatus includes a sample addition station for adding a sample to a test column in the apparatus, a reagent station, a washing station, a detection station for detecting signals on the snares of the test column due to the presence of the predetermined known materials in the sample, and conveying means for conveying the test column from the sample addition station to the reagent station, washing station, and detection station. The test sample is introduced into a test column which has at least two snares for capturing the predetermined known materials, and the snares are separate spatially one from another. Each snare has a capture material specific to the associated predetermined known material. The detection station has a plurality of detectors for detecting signals on the snares of the test column due to the presence of the predetermined known materials in the sample.

Abstract: A method for the transfer of molecules into cells and apparatus for performing the method.

Abstract: Methods and apparatus are provided for the recovery of nucleic acids from a nucleic acid-containing material by which nucleic acids can be rapidly and easily recovered at a high purity without deteriorating the yield. The methods are composed of step 1 for promoting the release of nucleic acids from a nucleic acid-containing material, step 2 for mixing the released nucleic acids with an accelerator substance for the binding of nucleic acids to a solid phase, step 3 for bringing the mixture in contact with a solid phase bondable to nucleic acids, step 4 for isolating the solid phase from a liquid, step 5 for washing the solid phase with a solution containing a salt, and a step 6 for eluting the nucleic acids from the solid phase. Accordingly, nucleic acids at a suitable purity for genetic tests or gene analyses can be rapidly and easily recovered without the use of hazardous substances.

Abstract: There is disclosed a method for introducing agents into the cytosol and/or plasma membrane of a cell. The method comprises the steps of: (a) coating at least a portion of a tip of a transferring means with a lipid; (b) bringing the lipid-coated tip of the transferring means into contact with the cell; and (c) transferring the contents of the transferring means into the cytosol and/or plasma membrane of the cell without entering the cytoplasm. Also disclosed is a transferring means for injecting agents into the cytosol and/or plasma membrane of the cell and a method of coating a tip of a transferring means with a lipid. A suitable packaging and a method for preparing the transferring means for use are also disclosed.

Abstract: An apparatus suitable for making a designer disease is disclosed. The apparatus comprises first, second, and third containers, each having two sections, I and II, separated by a semipermeable material through which a microbe can pass but cells from target and non-target populations cannot pass, and an entrance and an exit to each section. The entrance to section I of the first and second containers are circulation entrances, the exits from section II of the first and second containers are circulation exits, and the entrance to and exit from section I of the third container is a circulation entrance and a circulation exit, respectively. Conduits form a loop by connecting the circulation exit of each container to the circulation entrance to another container. A pump moves fluid around the loop and microbes in the fluid are mutated. A method of making a designer disease using that apparatus is also disclosed.

Abstract: The subject invention relates to improvements in nucleic acid isolation, and more particularly, relates to modifications to the subtractive hybridization method and to reagents such as oligonucleotides that are useful when performing the method.

Abstract: In a vector purification device, bacteria containing vectors are cultured in a culture medium in a culture tank, the culture medium is concentrated by filtration with a first TFF film, and the concentrated culture medium is replaced with a buffer solution by filtering a mixture of the culture medium and the buffer solution by the TFF film while supplying the buffer solution from a buffer tank. The bacteria subjected to bacteriolysis by an alkali solution supplied from an alkali tank are passed through a second TFF film to remove undesired substances. Since the TFF films are used in place of a centrifugal separator for concentration or the like, a series of operations can be carried out continuously in a closed system. Further, a crudely purified vector solution is treated with a surfactant to separate vector DNAs from endotoxins as separate layers, and the endotoxins are removed.

Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.

Abstract: The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and stimulate cells that maximizes stimulation and/or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and/or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and/or receptor signaling enhancement.

Abstract: The present invention provides a microinjection assembly including a microscope, a microinjection system comprising a micromanipulator, a micropipette and a piezo-electric oscillator, and an obliquely angled macro monitoring unit. The present invention also provides methods of microinjecting the germinal disk of an avian egg, thereby delivering a transgenic nucleus, spermatozoon or isolated nucleic acid to the avian embryo. The avian ovum may be returned to a female bird for hard-shell deposit and laying of the egg for hatching as a transfected bird.

Abstract: An apparatus suitable for making a designer disease is disclosed. The apparatus comprises first, second, and third containers, each having two sections, I and II, separated by a semipermeable material through which a microbe can pass but cells from target and non-target populations cannot pass, and an entrance and an exit to each section. The entrance to section I of the first and second containers are circulation entrances, the exits from section II of the first and second containers are circulation exits, and the entrance to and exit from section I of the third container is a circulation entrance and a circulation exit, respectively. Conduits form a loop by connecting the circulation exit of each container to the circulation entrance to another container. A pump moves fluid around the loop and microbes in the fluid are mutated. A method of making a designer disease using that apparatus is also disclosed.

Abstract: Methods, systems, kits for carrying out a wide variety of different assays that comprise providing a first reagent mixture which comprises a first reagent having a fluorescent label. A second reagent is introduced into the first reagent mixture to produce a second reagent mixture, where the second reagent reacts with the first reagent to produce a fluorescently labeled product having a substantially different charge than the first reagent. A polyion is introduced into at least one of the first and second reagent mixtures, and the fluorescent polarization in the second reagent mixture relative to the first reagent mixture is determined, this fluorescent polarization being indicative of the rate or extent of the reaction.

Abstract: A unit dose test device for a nucleic acid amplification reaction has the form of a elongate disposable test strip. The test strip includes a dual-chamber reaction vessel pre-loaded with nucleic acid amplification reaction reagents, and a plurality of wells for processing a reaction occurring in the reaction vessel.

Abstract: A package for hybridization includes a substrate and a housing. The substrate has a first surface that includes an array of probes having biological polymers immobilized thereon. The housing includes a fluid cavity constructed and arranged for hybridization of a target to a probe of the probe array located inside the fluid cavity. The housing also includes a bar code.

Abstract: The present invention generally provides novel apparatuses for rapidly and efficiently carrying out repeated hybridizations of a target nucleic acid to an array of nucleic acid probes. The apparatus generally includes a fluid delivery system, a fluid mixing system, a temperature control system and a process control system integrated into a single device.