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:
A method for improving the reliability and/or accuracy of physical measurements obtained from array hybridization studies performed on an array having a large number of genomic samples uses a small number of replicates insufficient for making precise and valid statistical inferences. This is overcome by estimating an error in measurement of a sample by averaging errors obtained when measuring the large number of samples or a subset of the large number of samples. The estimated sample error is utilized as a standard for accepting or rejecting the measurement of the respective sample. The samples may be independent or dependant in that correlated across two or more conditions.
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:
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.