Abstract: A dual inlet microchannel device and a method for using the device to perform a flow-through kinetic assay are described. A microplate having an array of the dual inlet microchannel devices and in particular their specially configured flow chambers is also described. Several embodiments of the dual inlet microchannel devices and specially configured flow chambers are also described.

Abstract: A screening device and a method are described herein which can automatically handle and measure (interrogate) a plurality of sensor carriers (i.e., multiwell plates, microplates) with multi-dimensionally arranged, temperature-compensated or temperature-compensatable optical sensors, while maintaining a substantially constant temperature gradient for a relatively long period of time around the optical sensors where temperature compensation has been performed on the sensor carriers.

Abstract: A container with a lid comprises a container portion (10) having an opening portion (11) for the loading or unloading of a sample or the like, a lid portion (20) that can be detachably fitted in said opening portion (11) so as to close the same, and a lever mechanism portion (30) for opening said lid portion (20) in a closed state using leverage. The lever mechanism portion (30) is composed of a lever portion (33) having a force-applied point (P) portion that is pressed by a finger and an action point (Q) portion that is pressed against an external periphery portion of said lid portion (20) when pressed with the finger so as to open the same, and a support portion (31, 32) for supporting said lever portion (33) via a thin-walled portion (35) that constitutes a fulcrum (O) portion, in a freely swinging manner. The lever mechanism portion (30) allows the lid portion (20) to be easily opened with one hand without putting much burden on the fingers even if it is very tightly closed.

Abstract: A screening system and method are described herein which provide a unique and practical solution for enabling label-free high throughput screening (HTS) to aid in the discovery of new drugs. In one embodiment, the screening system enables direct binding assays to be performed in which a biomolecular interaction of a chemical compound (drug candidate) with a biomolecule (therapeutic target) can be detected using assay volumes and concentrations that are compatible with the current practices of HTS in the pharmaceutical industry. The screening system also enables the detection of bio-chemical interactions that occur in the wells of a microplate which incorporates biosensors and surface chemistry to immobilize the therapeutic target at the surface of the biosensors. The screening system also includes fluid handling and plate handling devices to help perform automated HTS assays.

Abstract: A mechanism for positionally restraining a microplate is disclosed. The mechanism is defined by a base having at least one surface with a receptacle for the insertion of a microplate into the base. Supports and/or positioning structures on a surface of the base have point contacts to restrain movement of the microplate in a stable position for repeatable optical detection measurements. The supports and/or positioning structures permit insertion of the microplate for an initial measurement, removal of the microplate for analytical manipulation, and re-insertion of the microplate to an exact position so as to allow analysis of precise comparative measurements by an optical reader.

Abstract: A system and method are described herein for self-referencing a sensor that is used to detect a biomolecular binding event and/or kinetics which occur in a sample solution flowing along side a reference solution in a micron-sized deep flow channel.

Abstract: A multi-channel swept wavelength optical interrogation system and a method are described herein that enable the interrogation of one or more biosensors which for example could be located within the wells of a microplate. In one embodiment, the optical interrogation system comprises: (a) a tunable laser that emits an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period; (b) a distribution unit that splits the optical beam into a plurality of interrogation beams; (c) an array of optical interrogation units that receive and direct the interrogation beams towards an array of biosensors; (d) the array of optical interrogation units receive a plurality of reflected interrogation beams from the array of biosensors; (e) a data processing device that receives and processes information associated with the reflected interrogation beams to determine for example whether or not there was a biochemical interaction on anyone of the biosensors.

Abstract: A screening device and a method are described herein which can automatically handle and measure (interrogate) a plurality of sensor carriers (i.e., multiwell plates, microplates) with multi-dimensionally arranged, temperature-compensated or temperature-compensatable optical sensors, while maintaining a substantially constant temperature gradient for a relatively long period of time around the optical sensors where temperature compensation has been performed on the sensor carriers.

Abstract: An optical interrogation system is described herein that can interrogate a label-independent-detection (LID) biosensor and monitor a biological event on top of the biosensor without suffering from problematical parasitic reflections and/or problematical pixelation effects. In one embodiment, the optical interrogation system is capable of interrogating a biosensor and using a low pass filter algorithm to digitally remove problematic parasitic reflections contained in the spectrum of an optical resonance which makes it easier to determine whether or not a biological event occurred on the biosensor. In another embodiment, the optical interrogation system is capable of interrogating a biosensor and using an oversampling/smoothing algorithm to reduce oscillations in the estimated location of an optical resonance caused by the problematical pixelation effect which makes it easier to determine whether or not a biological event occurred on the biosensor.

Abstract: The present invention includes several methods for modifying the current processes of manufacturing optical sensing microplates that use continuous waveguide films to reduce/eliminate crosstalk between the biosensors that are incorporated within wells. The methods include (1) physically deteriorating/removing the waveguide film between individual biosensors; (2) chemically depositing highly absorbing materials within the waveguide film between individual biosensors; (3) patterning disordered (scattering) regions between the diffraction gratings that define individual biosensors; (4) using a specific mask and depositing individual patches of waveguide film, where each patch defines at least one biosensor. Each of these methods and several other methods described herein prevent the propagation of light between individual sensing regions, thereby eliminating optical crosstalk between the biosensors. The present invention also includes the resulting microplate.

Abstract: An optical reader system and method are described herein that can detect a lateral and/or angular misalignment of one or more biosensors so that the biosensors can be properly re-located after being removed from and then reinserted into the optical reader system. In one embodiment, the biosensors are incorporated within the wells of a microplate.

Abstract: An optical interrogation system and method are described herein that are capable of detecting and correcting a positional misalignment of a label independent detection (LID) microplate so that the LID microplate can be properly interrogated after being removed from and then re-inserted back into a microplate holder/XY translation stage.

Abstract: A closed flow-through microplate is described herein that can be used to perform high-throughput kinetic flow-through assays to detect biomolecular interactions like material bindings, adsorptions etc. . . that is helpful for example with testing new drugs. A method for manufacturing the closed flow-through microplate is also described herein.

Abstract: A reference microplate is described herein which can be used to help calibrate and troubleshoot an optical interrogation system. In one embodiment, the reference microplate has a frame with an array of wells each of which contains an optical biosensor and each optical biosensor is at least partially coated with a substance (e.g., elastomer, optical epoxy). In another embodiment, the reference microplate in addition to having its optical biosensors at least partially covered with a substance (e.g., elastomer, optical epoxy) also has a controllable heating device attached thereto which is used to heat the optical biosensors.

Abstract: An optical interrogation system and a method are described herein that enable the interrogation of one or more biosensors which can be located within the wells of a microplate. In one embodiment, the optical interrogation system has a tunable laser, N-fiber launches, N-lenses and N-detectors that are set-up to interrogate N-biosensors. In another embodiment, the optical interrogation system has a tunable laser, N-fiber launches, N+1 lenses and N-detectors that are set-up to interrogate N-biosensors.

Abstract: An optical reader system is described herein which has a single mode (SM) optical fiber launch/receive system that uses one or more SM optical fibers to interrogate a biosensor and does not use multimode (MM) optical fibers to interrogate the biosensor. The use of the SM optical fiber launch/receive system effectively reduces angular sensitivity, reduces unwanted system reflections, improves overall angular tolerance, and improves resonant peak reflectivity and resonant peak width. Two specific embodiments of the SM optical fiber launch/receive system are described herein which include: (1) a dual fiber collimator launch/receive system; and (2) a single fiber launch/receive system that interrogates the biosensor at a normal incidence.

Abstract: The present invention relates to methods for prevention and treatment of bone-related or nutrition-related disorders using a GLP molecule or GLP activator either alone or in combination with another therapeutic. The present invention also encompasses methods of diagnosing or monitoring the progression of a disorder. The invention also encompasses methods of monitoring the effectiveness of treatment of the invention.

Abstract: The disclosure concerns stable expression systems for production of a protein comprising: a) a species of Acanthamoeba as a host organism; b) a DNA vector which comprises a selection marker gene which codes for a protein which, after transformation of the host organism, allows selection of positive transformants, where expression of the selection marker gene is controlled by at least one genetic regulatory element which is homologous in the host organism; and c) a DNA vector which comprises a heterologous gene for the expression of a heterologous protein, where the expression of the protein is controlled by at least one genetic regulatory element which is homologous to the host organism.

Abstract: The present invention provides methods of determining aggregation of &agr;-synuclein, which are a hallmark of Lewy body diseases such as Parkinson's disease. Also disclosed are inhibitors of the aggregation, including magnesium and &agr;-synuclein binding peptides. The inhibitors are useful in the treatment of Lewy body diseases.

Abstract: Highly efficient cationic liposomes have been developed as an improved delivery system for biologically-active reagents. A novel structure, the sandwich liposome, is formed and comprises one or more biologically active agents internalized between two bilomellar liposomes. This structure protects the incoming agent and accounts for the high efficiency of in vivo delivery and for the broad tissue distribution of the sandwich liposome complexes. These novel liposomes are also highly efficient carriers of nucleic acids. By using extruded DOTAP:cholesterol liposomes to form complexes with DNA encoding specific proteins, expression has been improved dramatically. Highest expression was achieved in the lung, while increased expression was detected in several organs and tissues.