Abstract: A method of identifying a therapeutic compound for treating cancer in a human subject, the method including: providing a device that measures cell-substrate impedance; culturing cancer cells in the at least two wells, wherein the cancer cells are obtained from a human subject and have a receptor tyrosine kinase (RTK) pathway; adding to a first well a proposed therapeutic compound that affects an RTK pathway and an RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells; and determining a difference in impedance or optionally in cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells of the human subject.

Abstract: Methods for identifying compounds that modulate cellular responses stimulated by IgE, which include providing an impedance-based system that monitors cell-substrate impedance of cells on a substrate; introducing cells to the substrate of the system; adding at least one test compound and IgE to the cells, wherein the at least one test compound is suspected of modulating cell responses stimulated by the IgE; adding an antigen to the cells; monitoring the cell-substrate impedance of cells on the substrate; and analyzing the cell-substrate impedance to evaluate whether the at least one test compound alters a cellular response to stimulation with the IgE.

Abstract: A system for detecting signal components of light induced by multiple excitation sources, which includes a flow channel having two spatially separated optical interrogation zones; a light illumination subsystem that directs each of two light beams of different wavelengths to a different zone of the optical interrogation zones; a detector subsystem that converts detected light into a total electrical signal having both modulated and unmodulated electrical signals; and a processor that determines signal components from the light detected from each of the optical interrogation zones.

Abstract: Methods of identifying whether a biologically active agent affects an oncogene addicted pathway within a cancer cell, by introducing a biologically active agent suspected of affecting an oncogene addicted pathway to a first well and a negative control to a second well, and introducing a stimulating agent that stimulates the oncogene addicted pathway to both wells; monitoring cell-substrate impedance of the two wells and optionally determining cell indices from impedance values; generating an impedance based curve for each of the two wells from the impedance values or from the cell indices; comparing the impedance-based curves to determine a degree of similarity; and if significantly different concluding the biologically active agent affects the oncogene addicted pathway within the cancer cells.

Abstract: Devices and methods for performing extracellular recording of cells, such as excitable cells, cardiomyocytes, and cardiomyocyte precursor cells is provided. An exemplary device includes a nonconductive substrate forming or provided as a base of one or more wells; a recording electrode positioned on the substrate within the well, wherein the recording electrode is accessible to cells when a cell sample is added to the device; and a reference electrode positioned within the well in a cell-free zone, the cell-free zone characterized as free from contact with cells when the cell sample is added to the device, thereby preventing contact between cells and the reference electrode.

Abstract: Devices, systems and methods for monitoring excitable cells, such as cardiomyocytes, on microelectrode arrays that couple the electro-stimulation of excitable cells to induce or regulate cardiomyocyte beating and the simultaneous measurement of impedance and extracellular recording to assess changes in cardiomyocyte beating, viability, morphology or electrophysical properties in response to a plurality of treatments.

Abstract: A system for monitoring cell-substrate impedance of excitable cells and monitoring the beating cycle of cardiomyocytes, the system including: a device for monitoring cell-substrate impedance at 20 millisecond time resolution, the device having one or more wells on a nonconductive substrate, wherein at least one well of the one or more wells comprises an electrode array fabricated on the substrate for measurement of cell-substrate impedance at 20 millisecond time resolution; an impedance analyzer that measures cell-substrate impedance from the at least one well at 20 millisecond time resolution; electronic circuitry that electrically connects the electrode array from the at least one well to the impedance analyzer; and a software program that analyzes the measured cell-substrate impedance.

Abstract: An optical engine its use in a bench top flow cytometer, the optical engine having a set of lasers, each focused horizontally along an x-axis to a same horizontal position and vertically along a y-axis to a different vertical position along a same excitation plane of a flow cell, a set of optics that separate fluorescence of a same wavelength range into different locations in a focal plane of collection optics according to the different lasers by which the fluorescent light is excited; and a detector that selectively detects light from the different locations thereby distinguishing between fluorescence emitted within the same wavelength range as excited by the different lasers.

Abstract: An optical engine for use in a bench top flow cytometer, the optical engine comprising a set of lasers; a different set of beam shaping optics for each laser, wherein each set comprises two lenses to adjustably focus light horizontally along an x-axis to a same horizontal position and vertically along a y-axis to a different vertical position along a same plane; collection optics for collecting fluorescence from the flow cell; filtration optics that filter the collected fluorescence from the flow cell into different detection channels according to wavelength ranges; and a detector for each detection channel that converts the filtered fluorescence to electrical signals, wherein electrical signals are processed so that the fluorescence from each laser at the different vertical positions is distinguished at the same detector.

Abstract: Use of impedance devices in methods of generating a time dependent cellular profiles (TCRP) for the modulation of oncogene addicted cells and comparing the impedance-based TCRP to controls or knowns to identify signature time dependent cellular profiles.

Abstract: A method of identifying a potential therapeutic compound that affects a Receptor Tyrosine Kinase (RTK) pathway in cancer cells, which includes: providing a device capable of measuring cell-substrate impedance; culturing cancer cells in serum-free media in at least two wells of the device; adding to a first well a proposed therapeutic compound that affects a RTK pathway and a RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells and optionally determining cell indices from the monitored cell-substrate impedance; and determining a difference in impedance or optionally cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells.

Abstract: Use of cell-substrate impedance based methods for screening for agonists of G-Protein Coupled Receptors (GPCRs) or inhibitors of a Receptor Tyrosine Kinases (RTKs), identifying compounds that affect GPCR or RTK pathways, validating molecular targets involved in a GPCR or RTK signaling pathways, monitoring dose-dependent functional activation of GPCR or RTK; determining desensitization of a GPCR and identifying a compound capable of affecting RTK activity in cancer cell proliferation.

Abstract: A method for assaying target molecules in a sample liquid, the method comprising: providing an impedance monitoring device operably connected to an impedance analyzer; adding a sample liquid suspected of having target molecules to the well thereby permitting binding of target molecules to the capture molecules; monitoring impedance of the well; and determining the presence, amount or concentration of target molecules in the liquid sample from the monitored impedance. The device includes a nonconducting substrate having a well, at least two electrodes fabricated on a bottom of the well and on a same plane, wherein the surfaces of the at least two electrodes are modified with capture molecules configured to bind target molecules in a liquid sample, and at least two connection pads electrically connected to the at least two electrodes.

Abstract: A system for monitoring impedance of excitable cells in vitro, which includes a device for monitoring cell-substrate impedance at 20 millisecond resolution, which includes a nonconductive substrate with one or more electrode arrays fabricated in one or more wells, wherein cell attachment on the substrate can result in a detectable change in impedance between electrodes within each electrode array; an impedance analyzer capable of impedance measurement at 20 millisecond time resolution; electronic circuitry that can engage said device and selectively connect said two or more electrode arrays of said device to said impedance analyzer; and a software program that controls said electronic circuitry and records and analyzes data obtained from said impedance analyzer.

Abstract: The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.

Abstract: A method of collecting cells from individual wells of a multi-well plate for use in flow cytometry, the method including adding a suspension of cells to wells of the multi-well plate; and aspirating cells from different wells according to a collection pattern into a flow cytometer, wherein the collection pattern is a sequential ordering of wells beginning at a middle region of the multi-well plate and continuing towards an outer region of the multi-well plate. The method preferably including rotating or agitating the multi-well plate between steps of aspirating cells from different wells. Exemplary collection patterns include spiral-square collection pattern and a nearest well to center collection pattern.

Abstract: The present invention relates to certain pyrrolopyrimidine derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for the treatment of tumors and related diseases related to the dysregulation of kinase (such as EGFR (including HER), Alk, PDGFR, but not limited to) pathways.

Abstract: The present invention relates to certain pyrrolopyrimidine derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for the treatment of tumors and related diseases related to the dysregulation of kinase (such as EGFR (including HER), Alk, PDGFR, but not limited to) pathways.

Abstract: The present invention relates to certain pyrrolopyrimidine derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for the treatment of proliferation disorders and other diseases related to the dysregulation of kinase (such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, BTK, FLT3(D835Y), ITK, JAK1, JAK2, JAK3, TEC and TXK) and/or the respective pathways.

Abstract: Systems and methods for improved monitoring of excitation-contraction coupling and excitable cells are provided, which provide millisecond time resolution. The system is capable of continuously monitoring excitation-contraction coupling in a relatively high-throughput manner. The system includes a device for monitoring cell-substrate impedance, an impedance analyzer capable of impedance measurements at millisecond time resolution, electronic circuitry that can engage the device and selectively connect two or more electrode arrays of the device to the impedance analyzer and a software program that controls the electronic circuitry and records and analyzes data obtained from the impedance analyzer.