Abstract: An exemplary cellular analysis system and method are disclosed that can determine epithelial cell membrane properties by fitting electrochemical impedance spectroscopy (EIS) measurements to (i) an intracellular circuit model having electrical property parameters of the epithelial cell membrane properties, including the apical, basolateral, and shunt pathways or (ii) an extracellular circuit model. The exemplary cellular analysis system and method can be used to measure membrane properties of epithelial electrophysiology that can beneficially be used to assess for transport dysfunction and/or evaluate cellular drug responses in disease models. An exemplary cellular analysis system and method are disclosed that can determine the polarization of epithelial cells in response to stimuli as a time-constant impedance-associated ratio (tau ratio) that can be used in a massively parallel screening system for drug discovery.

Abstract: An exemplary embodiment of the present disclosure provides a system comprising a pipette tip manipulable between a sample area and an active agent exposure zone and a controller configured to manipulate the pipette tip between the sample area and the active agent exposure zone, wherein when the pipette tip comprises at least a portion of a biological sample target, the controller is further configured to isolate at least a portion of the biological sample target from one or more biological sample targets. Also disclosed is a method for detecting an effect of an active agent on a cell, by forming a high-resistance seal between a cell and an apertured surface, isolating at least a portion of the cell, translocating the apertured surface in one or more translations within an x-plane, a y-plane, a z-plane, or combinations thereof, and exposing the portion of the cell to an active agent.

Abstract: In an automated method for in vivo multiple cell patch clamping, cell patch clamping devices are automatically moved into position and targeted to multiple corresponding cells. Cell contact is determined by analyzing the temporal series of measured resistance levels at the clamping devices as they are moved. The difference between successive resistance levels is computed and compared to a threshold, which must be exceeded for a minimum number of computations before neuron contact is assumed. Pneumatic control methods are used to achieve cell-attached or gigaseal formation and subsequent cell break-in, leading to whole-cell patch clamp formation. An automated robotic system automatically performs patch clamping in vivo, automatically detecting cells according to the methodology by analyzing the temporal sequence of electrode impedance changes.

Abstract: In an automated method for in vivo multiple cell patch clamping, cell patch clamping devices are automatically moved into position and targeted to multiple corresponding cells. Cell contact is determined by analyzing the temporal series of measured resistance levels at the clamping devices as they are moved. The difference between successive resistance levels is computed and compared to a threshold, which must be exceeded for a minimum number of computations before neuron contact is assumed. Pneumatic control methods are used to achieve cell-attached or gigaseal formation and subsequent cell break-in, leading to whole-cell patch clamp formation. An automated robotic system automatically performs patch clamping in vivo, automatically detecting cells according to the methodology by analyzing the temporal sequence of electrode impedance changes.

Abstract: Described herein in several embodiments are a system, method and apparatus for measuring platelet thrombus volume of a blood sample. In some embodiments, the present invention comprises a microfluidic apparatus having a blood input that receives the blood sample and a plurality of flow channels. In some embodiments of the present invention, each flow channel has a non-stenotic region that receives a portion of the blood sample from the blood input and a stenotic region for creating a discrete initial shear rate in the flow channel. The initial shear rate in the flow channel can be from approximately 500 s?1 to approximately 13000 s?1. The stenotic region, or a narrowing or stricture of the flow channel passageway, is used to simulate a partial blockage of a blood vessel that can result in thrombosis within the blood vessel.