Abstract:
A system for performing automated cell screening in drug discovery includes an automated microscope (100), a fast autofocus device, and a digital imaging system (500). Processes are implemented in software through which relevant cellular material is segmented and quantified with minimal user interaction. Improvements in the following areas: known methods for image processing are implemented in such a way that automated segmentation is achieved; sets of known measurements (pixel counting, etc.) are implemented as methods which demonstrate aspects of biology in a reliable fashion; components for automated positioning, focusing, imaging and processing of a multiplicity of samples are integrated as systems within which the segmentation and measurement methods may be mounted; and components and methods are adapted into systems which yield more highly automated and more rapid cell screening.
Abstract:
An analytical process is disclosed, for discriminating data acquired from samples with overlapping distributions, and for improving and assessing the statistical validity of hybridization signal in arrays of assays. The process includes method of convolving data into two or more discrete probability density functions representing signal and nonsignal, discrete fluors, or other convolved independent variables. The system uses the probability density functions to assign hybridization signals, objectively, to one of the modeled distributions. Subsequent processes assess variability inherent to the arrays, and use this assessed variation to establish reliability scores and confidence limits for complete hybridization arrays, and for discrete hybridization assays within arrays.
Abstract:
The present invention relates to an apparatus and method for imaging time resolved fluorescence in biochemical and medical samples. In a primary aspect, the device includes a lens of large aperture, a flash lamp in the illumination path, a fast-acting solid state shutter or a gated detector in the emission path, a device for delivering homogenous monochromatic illumination to a plurality of wells distributed within a microwell plate, a digital camera of high quantum efficiency, and a computer. under computer control, the lamp is pulsed at short intervals. The fast-acting emission shutter or gated detector operates to limit exposure of the camera to a period some microseconds after the extinction of each lamp pulse, during which only delayed fluorescence is transmitted to the camera. The invention achieves simultaneous time resolved imaging of a plurality of samples, with high sensitivity and high throughput.
Abstract:
The invention relates to a multichip module comprising a base chip (10), a top chip (16), whose thickness is less than 100 mu m, and an adhesive layer (22) which is placed between the base chip (10) and the top chip (16), and both chips are mechanically joined to one another. An electrically insulating planarization layer (24) is provided such that the top chip (16) is embedded in the planarization layer (24). A through hole (26a) in the planarization layer (24) is filled with an electrically conductive material, is connected, in an electrically conductive manner, to a connection surface of the base chip (10), and is connected, in an electrically conductive manner, to a connection surface (20) of the top chip (16) via a metallization (28, 30). Through holes (26a, 26b) in the planarization layer (24) enable the production of all connections between the chips, between the base chip or between the top chip and external contacts of the multichip module in a manner that is independent of the individual chips and while using conventional semiconductor processing steps.
Abstract:
A specimen containment system is disclosed which optimizes the optical properties of the specimen holders (wells) for imaging in order to enhance the relevant signal, relative to background. A family of well plates all have the inherent properties of: i) minimizing reflections from an excitation source into an imaging detector; ii) minimizing the concentration of excitation into intense and localized sources (lensing); and iii) allowing an epi-illuminating excitation beam to penetrate both central and lateral wells effectively. The well plates are made of a material that has or is treated to have minimal inherent fluorescence and minimal reflection properties. The well chambers are constructed to be depth-wise asymmetric (for example, sloping well surfaces) and to have cross-sectional irregularity. The bottom walls of the wells may also be formed with a ridge or made transparent so as to minimize reflections of incident light therefrom.
Abstract:
An electronic imaging system is disclosed, for assessing the intensity of colorimetric, fluorescent or luminescent signal in a matrix consisting of wells, microwells, hybridization dot blots on membranes, gels, or other specimens. The system includes a very sensitive area CCD detector (18), a fast, telecentric lens (22) with epi-illumination (44), a reflective/transmissive illumination system, an illumination wavelength selection device (34), and a light-tight chamber (24). A computer and image analysis software are used to control the hardware, correct and calibrate the images, and detect and quantify targets within the images.
Abstract:
An electronic imaging system is disclosed which provides a very high level of sensitivity to enable imaging of biological and chemical specimens at low light levels. The system includes an integrating cooled CCD camera which has an image intensifier coupled thereto. With the present invention, light from the specimen is amplified by the intensifier, and the amplified light is integrated onto the cooled CCD camera over a period of time lasting for at least one second. At the end of the integration period, the camera is read out to a dedicated controller or imaging apparatus to create a digital image of the specimen. Frame averaging can be used within the imaging apparatus or controller, to improve the signal to noise ratio and increase the dynamic range of the camera. In addition, shading correction can be applied to remove spatial variations in camera sensitivity, to provide a homogeneous image background.