Abstract: Methods and apparatus for genome analysis are provided. A microfabricated structure including a microfluidic distribution channel is configured to distribute microreactor elements having copies of a sequencing template into a plurality of microfabricated thermal cycling chambers. A microreactor element may include a microcarrier element carrying the multiple copies of the sequencing template. The microcarrier element may comprise a microsphere. An autovalve at an exit port of a thermal cycling chamber, an optical scanner, or a timing arrangement may be used to ensure that only one microsphere will flow into one thermal cycling chamber wherein thermal cycling extension fragments are produced. The extension products are captured, purified, and concentrated in an integrated oligonucleotide gel capture chamber. A microfabricated component separation apparatus is used to analyze the purified extension fragments.

Abstract: The present invention provides methods for assaying binding of compounds to G-quadruplex structures. Also provided are methods for screening candidate compounds for use as modulators of G-quadruplex activity, and methods for screening candidate compounds for telomerase inhibitory activity. The invention further provides novel compounds useful in the assays of the invention.

Abstract: The present invention provides a biochip for testing biological substances comprising a plurality of binding sites, optical means for determining a specific binding event at each binding site, wherein the plurality of binding sites and the means for determining a specific binding event at each binding site are monolithically integrated into a single chip which is electrically powered and produces electrical signals in response to binding events at each binding site. The means for determining a specific binding event can include a micro-cavity light source formed in a semiconductor layer and a photodetector formed in the same semiconductor layer and further include a grating assisted vertical planar waveguide coupler for in-situ monitoring hybridization dynamics at each binding site via associated changes in refractive index.

Abstract: A biochip, a platform which composes the biochip, and a stage which composes the platform. The biochip is for detecting analytes in a test sample. The platform comprises a stage. The stage of the invention includes a carrier.

Abstract: Methods for conducting an assay to detect nucleic acid hybridization are disclosed. In particular, the fabrication of a carbon electrode suited to nucleic acid hybridization detection is described. In some preferred embodiments, a micro array of carbon electrodes is constructed using photolithography. The final step in the photolithography process involves developing a solder mask with an alkaline solution. The alkaline solution oxidizes the carbon surface producing surface carboxylic acid groups. The surface carboxylic acid groups are reacted with EDC or DCC and NHS to produce NHS esters. Immobilization of NEUTRAVIDIN® onto the electrode surface is effected by reaction with the surface NHS ester groups. A biotinylated probe DNA molecule is then attached to the electrode via binding between the biotin group and the immobilized NEUTRAVIDIN®. The resulting electrode can be used to detect hybridization between the probe DNA and complementary target DNA.

Abstract: A method and apparatus for separating molecules comprises placing different kinds of molecular species onto a probe; and introducing an electric field between the probe and a surface in proximity with the probe so that the different kinds of molecular species may be separated, wherein the different kinds of molecular species have differing mobilities, and wherein the different kinds of molecular species may be separated according to their differing mobilities, such that molecular species that have different mobilities migrate along the probe at different speeds towards the surface. The molecular species may comprise molecules. Alternatively, the molecular species may comprise molecular assemblies, wherein the molecular assemblies may comprise at least one of cells, bacteria, and viruses.

Abstract: The invention relates to a method of reading, detecting or quantifying at least one biological reaction, on a support, between either a recognition molecule and a labeled target molecule or between a target molecule and a labeled detection molecule. The inventive method comprises treating the support under physicochemical conditions that allow the following: either the separation of the recognition molecule and the labeled target molecule or the separation of the target molecule and the labeled detection molecule. The inventive method further comprises producing images before and after the physicochemical treatment that can be used to determine the specific and non-specific bindings between the different molecules. The invention also relates to hybrids and complexes used in the inventive method and to a biochip containing the same which is used to carry out the inventive method. The invention is particularly suitable for use in the field of diagnosis.

Abstract: Techniques are described for the detection of multiple target species in real-time PCR (polymerase chain reaction). For example, a system comprises a data acquisition device and a detection device coupled to the data acquisition device. The detection device includes a rotating disk having a plurality of process chambers having a plurality of species that emit fluorescent light at different wavelengths. The device further includes a plurality of removable optical modules. Each of the removable optical modules is optically configured to excite the species and capture fluorescent light emitted by the species at different wavelengths. A fiber optic bundle coupled to the plurality of removable optical modules conveys the fluorescent light from the optical modules to a single detector.

Abstract: A method of mass-producing minute structures such as biochips, protein chips, quantum dots, and quantum chips involves arranging an antigen two-dimensionally on a board and arranging probes two-dimensionally facing the same direction so that the binding sites of the probes may bind to the antigen. An inorganic substance such as Ni is deposited on the board from the upper side of the probes by sputtering or evaporation to form a thin film layer and on the top surface of the flatly formed thin film layer, a supporting layer is formed by separating out the same inorganic substance using electrotyping. Then, by peeling the thin film layer and the supporting layer off of the board together, the mother stamper having cavities for the patterns of biomolecules is obtained.

Abstract: The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the first set differs from all other tetramers in the first set by at least two nucleotide bases, (2) no two tetramers within the first set are complementary to one another, (3) no tetramers within the first set are palindromic or dinucleotide repeats, and (4) no tetramer within the first set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units.

Abstract: Devices for the electrochemical detection of a nucleotide sequence in a fluid are described that include (a) a working electrode and a counter-electrode wherein the working electrode is attached to a biopolymer that has a specific affinity with the nucleotide sequence to be detected; (b) an exchangeable analysis cassette for introducing the fluid wherein the working electrode and the counter-electrode are arranged in the analysis cassette and can be contacted with the fluid; (c) a portable computer arrangement electrically connected with the analysis cassette containing a display and an energy source independent of an electrical supply net and (d) a temperature-regulating element for cooling and/or heating the fluid in the cassette, which is fed from the energy source. Analysis cassettes, systems of analysis cassettes, supplemental modules, and methods for producing analysis cassettes are also described.

Abstract: A novel hybridization device that improves the efficiency and consistency of microarray hybridization reactions by achieving a greater degree of internal mixing of target solution. The device provides a gasket-and-cover-type chamber wherein solution mixing is achieved by the creation of a multitude of microbubbles. One or more of the inner walls that define the chamber contain bubble-rupturing elements that extend into the chamber and terminate in sharp edges. They are typically located on opposite sides of a rectangular chamber and are pointed in a direction opposing bubble movement. Their interference with larger bubbles causes their breakup into microbubbles which travel separate and distinct paths as a result of external agitation and thereby provide improved solution mixing that results in a uniform distribution of target molecules to the probe molecules bound to the substrate. The sensitivity and consistency of the hybridization reaction is significantly increased.

Abstract: Disclosed are arrays for monitoring ecosystems, such as bodies of water, and methods and systems for making such arrays. In one embodiment, the array may include a plurality of oligonucleotides immobilized at known locations on a substrate, such that each location on the array is an oligonucleotide having a sequence derived from a single, predetermined operational taxonomic unit (OTU). The sequences immobilized on the array may be from known, or unknown organisms. Also disclosed are methods for identifying and isolating bioindicators diagnostic of specific ecosystems. The arrays and bioindicators of the invention may be used for rapid, and continual monitoring of ecosystems.