Abstract: A micro-machined nuclear transfer array (NTA) provides high-throughput transfer of nuclei between two cells. Donor cells containing the nuclei to be transferred are placed in microwells positioned adjacent to microwells containing the recipient biological cell. The microwells are contained within an upper chamber patterned with parallel rows of microwells of the diameter of the cell of interest. An injection port is formed in the bottom of the microwells through which nuclei may pass during transfer. The NTA also contains a lower chamber having a second array of capture wells of similar dimension and in register with the upper chamber for receiving the nuclei removed from the cell in the upper chamber. Nuclei are removed from the donor cells in the upper chamber, transferred to capture wells in the lower chamber, and inserted into the recipient biological cells of the upper chamber.

Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.

Abstract: A method and apparatus for fabricating an array of biopolymers on a substrate using a biopolymer or biomonomer fluid, and using a fluid dispensing head. The head has at least one jet which can dispense droplets onto a substrate, the jet including a chamber with an orifice, and including an ejector which, when activated, causes a droplet to be ejected from the orifice. The method includes positioning the head with the orifice facing the substrate. Multiple droplets of the biopolymer or biomonomer fluid are dispensed from the head orifice so as to form an array of droplets on the substrate. A gas flow is directed through a venturi which has a throat opening communicating with the dispensing head chamber. A venturi control valve which particularly communicate with an outlet of the venturi, is adjusted to alter the chamber pressure. The venturi may be driven by a source of inert anhydrous compressed gas which assists in maintaining fluid in the head isolated from moisture.

Abstract: The invention provides methods of monitoring expression levels of different polymorphic forms of a gene. Such methods entail analyzing genomic DNA from an individual to determine the presence of heterozygous polymorphic forms at a polymorphic site within a transcribed sequence of a gene of interest. RNA from a tissue of the individual in which the gene is expressed is then analyzed to determine relative proportions of polymorphic forms in transcript of the gene. Having identified alleles of a gene that are expressed at different levels, the alleles can be further analyzed to locate a second polymorphism that has a causative role in the different expression levels. The methods are amenable to analyzing large collections of genes simultaneously using arrays of immobilized probes.

Abstract: The invention relates to a method for transferring, for instance, a biological material arranged in a given pattern, whereby the biological material is brought into contact with needles placed on the head of a robot and the biological material is transferred to a support, whereby the needles are hard metal needles fitted with a biocompatible coating. The biocompatible coating preferably consists of metal-nitrogen compounds. Preferably, an anticorrosion coating is applied underneath the biocompatible coating. Once the biological material has been arranged in a given pattern, the needles mounted on the robot head are arranged according to the same pattern. Preferably, the pattern corresponds to the pattern of the arrangement of microtitre plate wells. The invention also relates to a robot head fitted with the inventive hard metal needles. Said robot head particularly forms part of a picking and/or a spotting robot.

Abstract: A biochemical reaction detection chip capable of controlling the temperature for biochemical reactions including hybridizations and its substrate. The function of the chip is performed by comprising a plurality of islands of a heat conducting material on the membrane of the substrate, the islands being spaced from each other and individually provided with temperature controllers, and the probes immobilized on the substrate.

Abstract: The invention provides methods of analyzing a nucleic acid in a target sample for variant alleles. In such methods, a first-labelled control sample and a second-labelled target sample are hybridized to at least one set of probes. The control sample comprises a homozygous reference allele. The target sample comprises the homozygous reference allele, or variant alleles differing from the reference allele at a locus, or one variant allele differing from the reference allele at the locus and one reference allele. The probes in the probe set span the locus and are complementary to the reference allele. After hybridization the intensity of first and second label bound to each probe in the set is measured. This information is then used to indicate the presence of one variant allele and one reference allele, or the presence of two variant alleles in the target sample.

Abstract: The present invention provides a nucleic acid detector for detecting a base sequences of a target DNA of interest, which comprises a DNA chip in which probe DNA and electrochemiluminescent material such as tris(2,2′-bipyridyl) metal complex, or derivatives thereof are immobilized on a surface of gold electrode; an electrochemical apparatus for applying a predetermined voltage to the DNA chip with respect to a reference electrode; and an optical measurement apparatus for measuring electrochemiluminescence generated from the DNA chip. The present invention also provides a method for producing the said detector for nucleic acids, and method for detecting nucleic acids using the same in a cost-saving way with high sensitivity.

Abstract: Methods and apparatuses are disclosed for detecting the presence of a test material in a test sample. The test sample is introduced into a test column which has at least two snares. One of the snares has a control capture material for detection of the presence of control. Each of other snares has a capture material specific to a corresponding test material for which detection being sought. The capture material will bind with the corresponding test material to form a bound material. The test column is then washed to remove materials which have not been bound to the capture materials. Finally, the presence of bound materials is detected on each of the snares. The method is useful for detection of a pathogen indicator in a test sample, particularly suitable for detection of DNA and RNA.

Abstract: Miniaturized, self-contained apparatus for conducting bio-chemical reactions and analyses is formed in a compact structure comprising a substrate which includes a plurality of reaction chambers and a plurality of analysis chambers which are in fluid communication with the reaction chambers. Independently controllable heaters and coolers are positioned in thermal contact with the reaction chambers to permit parallel processing of biological samples at different temperature cycles. The apparatus is especially useful for performing and analyzing the results of a polymerase chain reaction.

Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.

Abstract: A method of manufacturing items in parallel. Selected samples of items to be manufactured are subjected to additional steps in a manufacturing process. If such sample items meet the requisite quality control standard, remaining items are subjected to further manufacturing steps. If the sample items which have been further processed do not meet the requisite quality control standard, the lot from which the samples do not undergo the additional manufacturing step. Invention provides an improved method of manufacturing in that it prevents unnecessary manufacturing steps.

Abstract: A gene sequencer, bio-compact disk and sample preparation methodology is described. Constant length oligonucleotides are prepared and, in conjunction with the bio-compact disk and apparatus described, used in gene sequencing and strategies therefor.

Abstract: An inertial impact drill for diverse applications in cytology such as in-vitro fertilization, genetic research, pharmaceutical research, cloning, etc., is designed to operate in conjunction with micropipettes, microelectrodes, and micromanipulators. The drill includes two opposing actuators, one version of which is comprised a plurality of individual piezoelectric elements, the other version is comprised of a plurality of electrostrictive elements. The actuators drive a small inertial mass to produce sharp short reciprocal movements of this mass. The movements of the inertial mass result in repetitive impacts that are transferred to the micropipette or a microelectrode, which is mechanically coupled to the body of the inertial impact drill. In addition, the impacts cause mechanical oscillation of the tip of a micropipette or a microelectrode at its resonant frequency that is higher than the repetition rate of the impacts.

Abstract: The invention concerns instruments for fast, selective replication of deoxyribonucleic acid (DNA) from biomaterial through polymerase chain reaction (PCR), working in individual duplication thermocycles. The invention consists of extremely brief cycle times of only a few seconds for the PCR reactions, generated, on the one hand, by reaction chambers for the reception of the reaction solution constructed of a pattern of fine capillaries in close proximity to heating and cooling elements in order to optimally accelerate the temperature setting in the reaction solution for the three temperature phases of the PCR duplication cycles and, on the other hand, by keeping the flow rates in the capillaries to a minimum during the amplification phase so that the polymerase reaction is not disturbed. The capillary pattern can be simply produced by means of microsystem technology.

Abstract: Methods of manufacture and devices for performing active biological operations utilize various structures to advantageously collect and provide charged biological materials to an array of microlocations. In one embodiment, a device includes focusing electrodes to aid in the direction and transport of materials from a collection electrode to an array. Preferably, one or more intermediate transportation electrodes are utilized, most preferably of monotonically decreasing size between the collection electrode and the array, so as to reduce current density mismatches. In another aspect, a flow cell is utilized over devices to provide containment of solution containing materials to be analyzed. Preferably, the volume of the flow cell is more advantageously interrogated through use of relatively large collection and return electrodes, such as where the area of those electrodes relative to the footprint of the flowcell is at least 40%.

Abstract: The present invention is directed to the method and apparatus for the cytoplasmic loading of macromolecules into living cells by an impact-mediated procedure that impacts the cells with a predetermined number of solid particles in a blast of propellant gas. More specifically, the present invention is directed to an impact-mediated procedure that is altered by gravitational conditions and is preferably carried out under hypergravity conditions. Further, the present invention is directed to an IML method and apparatus for consistently and reproducibly loading macromolecules into the cytoplasm of living cells via membrane wounding at significantly higher efficiencies than can be accomplished using existing methodologies. The IML procedure directs a blast of propellant gas through a rupturable membrane on which solid particles are supported in order to achieve insertion of a predetermined number of particles into the propellant blast.