Abstract: A sample holder comprises a substrate microfabricated to define a multiplicity of microscopic islands defining sample support surfaces. At least one sump separates adjacent island surfaces and inhibits transport of samples between adjacent island surfaces.

Abstract: Novel peptide nucleic acids and novel linked peptide nucleic acids, form triple stranded structures with nucleic acids. The peptide nucleic acids include ligands such as naturally occurring nucleobases attached to a peptide backbone through a suitable linker. Other nucleobases including C-pyrimidines and iso-pyrimidines can be used as the ligands in Hoogsteen strands to increase binding affinity. Two peptide nucleic acid strands are joined together with a linker to form a bis-peptide nucleic acid. The individual strands of the peptide nucleic acids in the bis compounds can be orientated either parallel or antiparallel to each other.

Abstract: A tandem time-of-flight mass spectrometer is described. The spectrometer includes a pulsed source of ions that focuses a packet of ions substantially within a predetermined mass-to-charge ratio range onto a focal plane in a flight path of the ions. An ion selector receives the focused packet of ions and selects ions substantially within the predetermined mass-to-charge ratio range and rejects substantially all other ions. An ion fragmentor that fragments a fraction of the selected ions is positioned in the flight path of the selected ions. A pulsed ion accelerator that accelerates the selected ions and fragments thereof is positioned in a flight path of the selected ions and fragments thereof after the ion fragmentor. An electrode is positioned in the flight path of the accelerated selected ions and fragments thereof after the pulsed ion accelerator. In operation, the electrode is biased with a time varying bias voltage that increases the energy of the fragments relative to the selected ions.

Abstract: The present invention is directed to apparatus and methods for rapid, automated, microscale sample analysis using pressure differentials. The invention includes an apparatus having intersecting channels for introduction of a sample and separation of that sample into its components. The sample introduction and separation channels preferably are etched in a microfabricated device, such as a microchip, to form a junction. Pressure gradients are applied to the channels to form a sample plug in the separation channel. The separation channel may have disposed within it a medium for separation of the components suspected to be contained in the sample. For example, with the proper medium, a voltage gradient may be applied along the separation channel to separate the components of the sample electrophoretically. The apparatus also may include means for detecting the components of the sample subsequent to separation.

Abstract: The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

Abstract: A tandem time-of-flight mass spectrometry including a pulsed ion generator, a timed ion selector in communication with the pulsed ion generator, an ion fragmentor in communication with the ion selector, and an analyzer in communication with the fragmentation chamber. The fragmentation chamber not only produces fragment ions, but also serves as a delayed extraction ion source for the analyzing of the fragment ions by time-of-flight mass spectrometry.

Abstract: The invention features an apparatus for the separation and analysis of proteins, which includes a sample input, a first liquid chromatography column, a multiport injection valve connecting the sample input to the column, a pump for providing variable pressure delivery of a solution to the column via the multiport valve, and a program for specifying a sequence of system control programs.

Abstract: A fluid connector which provides a low fluid dead volume face seal capable of withstanding high pressures for coupling a fluid conduit to a microfluidic device. The fluid connector includes a housing, a clamping member, a first load support surface and a sealing member. The sealing member preferably includes first and second fluidically connected bores of different diameters so the fluid conduit may be retained within the larger diameter bore. The sealing member is positioned so that the smaller diameter bore interfaces with a port of the microfluidic device. In operation, the clamping member supplies an axial force to the first load support surface which is operatively coupled to the fluid conduit. When an axial force is transferred to the fluid conduit, the face of the fluid conduit at one end seals against the pliant portion of the sealing member while simultaneously urging the sealing member against the surface area surrounding the port of the microfluidic device to create a fluid-tight face seal.

Abstract: A time-of-flight mass spectrometer for measuring the mass-to-charge ratio of a sample molecule is described. The spectrometer provides independent control of the electric field experienced by the sample before and during ion extraction. Methods of mass spectrometry utilizing the principles of this invention reduce matrix background, induce fast fragmentation, and control the transfer of energy prior to ion extraction.

Abstract: A method is disclosed for the preparation of novel PNA synthons compatible with DNA synthetic reagents and instrumentation. Accordingly, the PNA synthons of this invention are particularly suitable for the preparation of PNA-DNA chimeras, among other oligomers. The PNA synthons are designed to have a protecting group strategy which is orthogonal and allows removal of the protecting groups under mild conditions. Generally, an acid labile protected backbone is coupled to a nucleobase side chain moiety to form the PNA synthon. A novel method for synthesizing the acid labile protected backbone also is described. In addition, novel compositions of matter are disclosed.

Abstract: A process and system are provided for forming and transporting precise small volumes of liquid samples by means of controlled gas pressures. As the controlled gas pressures are changed at a multiplicity of control points in the fluid circuit, transitions take place involving the transport of small liquid samples. This transport is arrested by the geometry of the fluid circuit to produce a new state, which state remains stable until another transition is initiated by a change in the multiplicity of controlled gas pressures. Various combinations of control elements are described for effecting formation of fixed liquid volumes, transporting, mixing, and removing entrained bubbles from small liquid samples.

Abstract: A method is disclosed for preparing novel PNA synthons having protecting groups capable of removal under mild conditions. The PNA synthons are prepared by coupling novel N-substituted nucleobase intermediates having carbamate protection of the exocyclic amino group of the heterocycle to an amino protected backbone or an amino protected backbone ester of the amino acid N-(2-aminoethyl)-glycine. By the method of this invention, the resultant PNA synthons can have orthogonal protection of the carbamate protected nucleobase and the amino protected backbone. The PNA synthons are useful in the synthesis of peptide nucleic acids (PNAs) and other oligomers such as PNA-DNA chimeras, and may be used in automated synthesizers. Novel compositions of matter are also disclosed. In addition, a guanine PNA synthon having selective carbamate protection of the exocyclic 2-amino group with the C6 carbonyl group unprotected is disclosed.

Abstract: A method is disclosed for preparing novel purine PNA synthons having protecting groups which may be removed under mild conditions. The purine PNA synthons generally are prepared by coupling purine derivatives having carbamate protection to a protected N-(2-aminoethyl)-glycine backbone. By a method of this invention, purine PNA synthons may have orthogonal protection of the carbamate protected purine and the protected backbone. The purine PNA synthons are useful in the synthesis of peptide nucleic acids (PNAs) and other oligomers such as PNA-DNA chimeras, and may be used in automated synthesizers. In practicing methods of the invention, novel compositions of matter also are disclosed.

Abstract: A method is disclosed for the preparation of novel PNA synthons compatible with DNA synthetic reagents and instrumentation. Accordingly, the PNA synthons of this invention are particularly suitable for the preparation of PNA-DNA chimeras, among other oligomers. The PNA synthons are designed to have a protecting group strategy which is orthogonal and allows removal of the protecting groups under mild conditions. Generally, an acid labile protected backbone is coupled to a nucleobase side chain moiety to form the PNA synthon. A novel method for synthesizing the acid labile protected backbone also is described. In addition, novel compositions of matter are disclosed.

Abstract: A time-of-flight mass spectrometer for measuring the mass-to-charge ratio of a sample molecule is described. The spectrometer provides independent control of the electric field experienced by the sample before and during ion extraction. Methods of mass spectrometry utilizing the principles of this invention reduce matrix background, induce fast fragmentation, and control the transfer of energy prior to ion extraction.

Abstract: Constructs of peptides and nucleic acid analogs conjugated together for transport across a lipid membrane and for delivery into interactive contact with intracellular polynucleotides are disclosed. Transport is effected through at least the exterior membrane of a cell, and most likely also through the walls of subcellular structures separated from the cytosol by lipid membranes, including the nucleus, mitochondria, ribosomes, etc. Peptide nucleic acid (PNA) analog sequences conjugated through a labile disulfide bond to transporting peptides, are intracellulary cleaved, and target mRNA (antigene) or dsDNA (antisense).

Abstract: A time-of-flight mass spectrometer for measuring the mass-to-charge ratio of a sample molecule is described. The spectrometer provides independent control of the electric field experienced by the sample before and during ion extraction. Methods of mass spectrometry utilizing the principles of this invention reduce matrix background, induce fast fragmentation, and control the transfer of energy prior to ion extraction.

Abstract: Disclosed are methods and apparatus for performing highly sensitive enzyme-amplified assays using channel electrophoresis of an enzyme having a biorecognition moiety. Combining a binding reaction of an analyte and an enzyme having a biorecognition moiety, and an electrophoretic separation which uses enzyme-amplified detection methodology, assay methods and apparatus are provided that offer simplicity, quantitative sensitivity and rapid analysis. Also disclosed are highly sensitive catalytically-amplified assays using a capillary electrophoresis format in which the binding reaction prior to electrophoresis is heterogeneous or homogeneous, and direct or competitive. The methods and apparatus for conducting sensitive automated catalytically-amplified assays using electrophoresis may be conducted in a microscale format.

Abstract: Compositions, methods, and apparatus for performing ultrafast binding assays by capillary electrophoresis or other electroseparation techniques are disclosed. In one embodiment, a first binding partner carries a detectable label and a second binding partner is modified to be highly charged. When used in combination with a sample containing an analyte with which both binding partners can interact and bind thereto, a three-membered complex is formed. The electrophoretic mobility difference between the unbound and complex-bound forms of labeled first binding partner is such that electroseparation and subsequent detection of an analyte can be accomplished. The compositions, methods, and apparatus disclosed herein also permit quantitative determination of the concentration of an analyte in a sample.

Abstract: The system for analyzing multiple samples includes a plurality of portable of sample supports each for accommodating a plurality of samples thereon, and an identification mechanism for identifying each sample location on each of the plurality of sample supports. The mass spectrometer is provided for analyzing each of the plurality of samples when positioned within a sample receiving chamber, and a laser source strikes each sample with a laser pulse to desorb and ionize sample molecules. The support transport mechanism provided provides for automatically inputting and outputting each of the sample supports from the sample receiving chamber of the mass spectrometer. A vacuum lock chamber receives the sample supports and maintains at least one of the sample supports within a controlled environment while samples on another of the plurality of sample supports are being struck with laser pulses.