Abstract: A method of determining a membrane potential is disclosed. The method comprises (a) determining a difference in fluorescence polarization of a charged fluorescent probe being distributed across the membrane; and (b) determining a potential of the membrane, wherein the potential is proportional to the difference in the fluorescent polarization.

Abstract: Described herein are embossing methods for forming pico liter well arrays (and other structures), arrangements of such pico liter well arrays, for example, in arrays of pico liter well areas, and methods of forming templates for such embossing. Also described as wells with a refractive index similar to that of an aqueous medium used for supporting cells in the wells.

Abstract: Disclosed is a method of studying floating living cell by confining the cells floating in an aqueous medium in picowells located on a bottom surface of a top wall of a chamber. Disclosed is also a picowell-bearing device for the study of cells comprising a chamber having at least one picowell on a bottom surface of the chamber. Also disclosed is a picowell-bearing device for the study of cells comprising a chamber having at least one picowell on an internal surface and at least one moveable wall, a force applicator configured to removeably apply a substantially uniformly distributed force around the periphery of the moveable wall in a direction to retain the moveable wall secured to the chamber.

Abstract: A device for studying individual cells including a picowell array (such as an array of microwells, dimples, depressions, tubes or enclosures) and a fluid reservoir in fluid communication with the picowells through channels is disclosed. Preferably, the device has a moveable lid that in one rest location allows loading of cells in the picowell array. Preferably the channels of the device are capillary channels. Also disclosed is a device for the automated study of cells including a picowell-bearing device having a picowell array with a moveable lid, a lid-moving component, at least one solution dispensing component and a control system functionally associated with the lid-moving component as well as with the solution dispensing component.

Abstract: A method for individually moving small objects, such as cells, from one location to another as well as a device for implementing the method is disclosed. A small object such as a cell is isolated at some initial location and moved to some destination location by the movement of the small object through a succession of intermediate locations until the small object arrives at the destination location. Also disclosed are methods of manipulating cells made possible by the method and device of the present invention.

Abstract: A method for individually moving small objects, such as cells, from one location to another as well as a device for implementing the method is disclosed. A small object such as a cell is isolated at some initial location and moved to some destination location by the movement of the small object through a succession of intermediate locations until the small object arrives at the destination location. Also disclosed are methods of manipulating cells made possible by the method and device of the present invention.

Abstract: A method for identifying images of wells in an image of a well-bearing object such as multiwell plates or picowell carriers is provided. An observation component, such as a camera, is used to approach focus of a focal point of a well-bottom. An image of the focal point is acquired. The image of the well-bottom focal point is then used as a reference point or used to define a reference point from which to identify the image of the well in the image of the well-bearing component and from which to delineate the borders of the well.

Abstract: A method of determining lymph node metastasis in a subject is disclosed, comprising determining at least one structural or functional parameter of a lymph node cell of a lymph node tissue of the subject, wherein an alteration in the at least one structural or functional parameter with respect to a lymph node cell of a healthy lymph node tissue is indicative of lymph node metastasis. Kits and articles of manufacture are also disclosed for determining lymph node metastasis in a subject as well as methods of diagnosing cancer in general.

Abstract: A method for identifying images of wells in an image of a well-bearing object such as multiwell plates or picowell carriers is disclosed using optical properties of the well-bearing object. An observation component, such as a camera, is used to approach focus of a focal point of a feature of the well-bearing component such as a well-bottom or well-wall or intersection of wells. An image of the focal point is acquired. The image of the focal point is then used as a reference point or used to define a reference point from which to identify the image of the well in the image of the well-bearing component and from which to delineate the borders of the well. In an aspect of the present invention, the well-bearing object is used as a wave-guide. Light escaping from a surface of the well-bearing object through discontinuous features such as well-intersections and well walls is used to delineate the borders of wells on the well-bearing object.

Abstract: The present invention broadly comprises a holding device for studying cells comprising at least one cavity adapted to receive cells in a medium consisting essentially of water, the cavity having a substrate and a generally inert wall, wherein the substrate includes a surface for receiving the medium, and wherein the surface includes a multiplicity of pico liter wells and is characterized in that the substrate is substantially translucent and has a refractive index equal to the refractive index of the medium The invention further comprises a method of making the holding device comprising providing a carrier plate, applying an adhesive layer to the carrier plate, depositing a curable substrate on the adhesive layer, applying a second layer of adhesive to the substrate, attaching a wall structure to the second layer of adhesive, forming a multiplicity of pico liter wells in the substrate, curing the substrate, and removing the template.

Abstract: A method for selecting specific cells from amongst a group of cells and a device for implementing the method, the method including the use of a radiation sensitive medium having a first state that does not immobilize cells and a second state that immobilizes cells wherein the radiation sensitive medium locally transforms from the first state to the second state upon exposure to radiation.

Abstract: A mulitwell plate having a plurality of picowells on the bottom of the wells of the plate as well as methods of producing the mulitwell plate are provided. Provided is also a method of handling living cells by providing an ordered array of living cells immobilized in a non-fluid matrix, contacting the living cells with a stimulus; and detecting a response to the stimulus. The present invention is also of a method of producing an ordered array of living cells.

Abstract: A method of determining a membrane potential is disclosed. The method comprises (a) determining a difference in fluorescence polarization of a charged fluorescent probe being distributed across the membrane; and (b) determining a potential of the membrane, wherein the potential is proportional to the difference in the fluorescent polarization.

Abstract: A device for the study of cells including a vessel with a current damper including a damping component substantially disposed within the vessel is disclosed. The damping component reduces or eliminates currents formed by the addition of materials such as liquids to the vessel to prevent the movement of cells resting on the bottom surface of the vessel.

Abstract: An Interactive Transparent Individual Cells Biochip Processor (ITICBP) device is described, which is useful for assessing a single, individual living cell at identifiable location or assessing group of cells each at identifiable location.

Abstract: A chip-device is provided for holding living cells in a plurality of wells disposed on the surface of a carrier, characterized in that the wells are configures to influence the proliferation of living cells in the wells, for example by changing the size of the wells, delaying or inhibiting cell-proliferation, delaying or inhibiting cell adhesion, or allowing cell proliferation inside or through components of the device itself. The influence on cell proliferation is achieved, for example, by coating the inside of the wells or fashioning the carrier from materials such as gels, especially hydrogels, polydimethylsiloxane, elastomers or polymerized para-xylylene molecules. Provided is also a gel-cover for any cell-holding device. Provided is also a method for making the devices of the present invention. Provided is also a method of manipulating cells by covering wells where the cells are held with gel or by increasing the size of wells wherein cells are held.

Abstract: A method for individually moving small objects, such as cells, from one location to another as well as a device for implementing the method is disclosed. A small object such as a cell is isolated at some initial location and moved to some destination location by the movement of the small object through a succession of intermediate locations until the small object arrives at the destination location. Also disclosed are methods of manipulating cells made possible by the method and device of the present invention.

Abstract: A method for identifying images of wells in an image of a well-bearing object such as multiwell plates or picowell carriers is provided. An observation component, such as a camera, is used to approach focus of a focal point of a well-bottom. An image of the focal point is acquired. The image of the well-bottom focal point is then used as a reference point or used to define a reference point from which to identify the image of the well in the image of the well-bearing component and from which to delineate the borders of the well.

Abstract: An isolated population of cells is provided. The isolated population of cells comprising at least one secretor cell capable of secreting a molecule and at least one sensor cell capable of producing a detectable signal upon being exposed to the molecule.

Abstract: A process for measuring enzymatic activity in an identified, isolated, intact, single, viable cell. Each of the viable cells is placed within individual identified locations on a carrier of a cytometer having means to measure enzymatic activity of a single viable cell placed in an identified location. The identified isolated cell is exposed to a substrate of an enzyme to be measured, and the rate of product formed or released following every exposure of the cell to same or different concentrations of the substrate is measured. The isolated cell may be exposed to a sequence of at least two different concentrations of the substrate, and for each exposure the rate of product formed or released, is measured.