Abstract: A solid state active pixel image sensor for back illumination by an electron beam is described. The image sensor comprises a thermal conduction layer for heat removal. The image sensor may also comprise a thinned silicon substrate on which an epitaxial layer is formed. The substrate may also be completely removed before or after application of the thermal conduction layer. The thermal conduction layer may comprise a metal, a metal compound, silicon, diamond or graphite.

Abstract: A hybrid arrangement of more than one electron energy conversion mechanism in an electron detector is arranged such that an image can be acquired from both energy converters so that selected high-illumination parts of the electron beam can be imaged with an indirectly coupled scintillator detector and the remainder of the image acquired with the highsensitivity/direct electron portion of the detector without readjustments in the beam position or mechanical positioning of the detector parts. Further, a mechanism is described to allow dynamically switchable or simultaneous linear and counted signal processing from each pixel on the detector so that high-illumination areas can be acquired linearly without severe dose rate limitation of counting and lowillumination regions can be acquired with counting.

Abstract: A hybrid arrangement of more than one electron energy conversion mechanism in an electron detector is arranged such that an image can be acquired from both energy converters so that selected high-illumination parts of the electron beam can be imaged with an indirectly coupled scintillator detector and the remainder of the image acquired with the high-sensitivity/direct electron portion of the detector without readjustments in the beam position or mechanical positioning of the detector parts. Further, a mechanism is described to allow dynamically switchable or simultaneous linear and counted signal processing from each pixel on the detector so that high-illumination areas can be acquired linearly without severe dose rate limitation of counting and low-illumination regions can be acquired with counting.

Abstract: There is disclosed a hybrid arrangement of more than one electron energy conversion mechanism in a detector arranged physically such that the electron image can be acquired from both energy converters in such a manner that selected high-illumination parts of the image can be imaged with an indirectly coupled scintillator detector and the remainder of the image acquired with the high-sensitivity/direct electron portion of the detector without readjustments in the beam position or mechanical positioning of the detector parts. Further, a mechanism to allow dynamically switchable or simultaneous linear and counted signal processing from each pixel of the image so that high-illumination areas can be acquired linearly without the severe dose rate limitation of counting and low-illumination regions can be acquired with counting, the switchover point determined by the dose rate at which signal quality breaks even between linear and counting modes.

Abstract: Methods are disclosed for removal of outlier pixels from a transmission electron microscopy camera image. One exemplary method includes establishing a desired exposure of n electrons per pixel; exposing the camera to a series of sub-frame exposures to produce a series of sub-frame images; calculating an average image signal of all sub-frame exposures in said series; establishing a threshold selected to achieve a desired number of false positives; evaluating each of said sub-frame exposures for pixels further away from said average than said threshold; and replacing pixels in each of said sub-frame images that exceed said threshold with said average to form corrected sub-frame images.

Abstract: Methods are disclosed for removal of outlier pixels from a transmission electron microscopy camera image. One exemplary method includes establishing a desired exposure of n electrons per pixel; exposing the camera to a series of sub-frame exposures to produce a series of sub-frame images; calculating an average image signal of all sub-frame exposures in said series; establishing a threshold selected to achieve a desired number of false positives; evaluating each of said sub-frame exposures for pixels further away from said average than said threshold; and replacing pixels in each of said sub-frame images that exceed said threshold with said average to form corrected sub-frame images.

Abstract: There is disclosed a hybrid arrangement of more than one electron energy conversion mechanism in a detector arranged physically such that the electron image can be acquired from both energy converters in such a manner that selected high-illumination parts of the image can be imaged with an indirectly coupled scintillator detector and the remainder of the image acquired with the high-sensitivity/direct electron portion of the detector without readjustments in the beam position or mechanical positioning of the detector parts. Further, a mechanism to allow dynamically switchable or simultaneous linear and counted signal processing from each pixel of the image so that high-illumination areas can be acquired linearly without the severe dose rate limitation of counting and low-illumination regions can be acquired with counting, the switchover point determined by the dose rate at which signal quality breaks even between linear and counting modes.

Abstract: A flow-through pressure regulator includes housing structure having a fuel inlet and a fuel outlet. A seal band is defined by the housing structure. A valve element is movable between open and closed positions. The valve element has a sealing surface that engages the seal band in the closed position to prevent fuel from passing from the fuel inlet to the fuel outlet. A compression spring is disposed in the housing structure. The spring is constructed and arranged to bias the valve element to the closed position in opposition to pressure exerted on the valve element by fuel at the fuel inlet. A guide member is associated with the valve element and is constructed and arranged to align the valve element with respect to the seal band. A calibration member is associated with an end of the spring and is constructed and arranged to pre-set compression of the spring.

Abstract: An apparatus for aligning a capillary column with one or more excitation fibers and with one or more optical lens elements for Capillary Electrophoresis. The apparatus includes two identical blocks having a plurality of grooves for positioning and aligning the capillary column with the one or more excitation fibers, and a plurality of lens seats for optically coupling the lens element with the capillary column. Each block includes a male and female part for mating the two identical blocks together.

Abstract: Methods are disclosed for correcting vertical line streaks in an interline or full-frame CCD. The method includes the step of subtracting an overscan row from each row of a previous image or from each row of a next image, such that each row of the final image contains the same readout smear effect and such that readout overscan rows contain the same smear information as each row of the final image. The method is also described for use with frame transfer CCDs.

Abstract: Methods are disclosed for operating a device having a high energy particle detector wherein the particles create first incoming traversal events, outgoing backscatter events, higher-order in and out events and incoming events caused by particles which backscatter out of the device, hit nearby mechanical structures and are scattered back into the device. Exemplary method steps include discriminating incoming traversal events from outgoing backscatter events, higher-order in and out events and incoming events by limiting dose rate to a level at ensures that separate events do not overlap and discriminating events from background and from other events based on total energy in each event; discriminating backscatter events from incoming traversal events based on electron path shape; or determining that a first event and a second event are coincident with each other and separating incoming form backscatter events based on electron path shape and energy level.

Abstract: A reusable bio-analysis cartridge that includes a built-in mechanism to track various parameters and usage data. The tracking mechanism includes a non-volatile rewritable memory “smart-key” that is associated with the cartridge to provide automatic tracking dedicated to the cartridge. The key may be physically coupled to the cartridge with good high voltage insulating properties. When the cartridge is used in an instrument, the associated key is inserted into an I/O interface to communicate with the instrument. The instrument may be configured to “authenticate” the cartridge and conduct an integrity check to determine if the particular cartridge has the correct properties (e.g., gel-chemistry, serial no., Patient I.D.) for the particular sample analysis to be conducted. Further, the instrument may communicate/record information concerning usage of the cartridge (e.g., usage history, test parameters, and perhaps test results).

Abstract: The present invention provides for an interface mechanism in a bio-separation instrument that makes interface connections to a multi-channel cartridge. The interface mechanism precisely positions the cartridge in relation to the support elements in the instrument (e.g., high-voltage, gas pressure, incident radiation and detector), and makes automated, reliable and secured alignments and connections between various components in the cartridge and the support elements in the supporting instrument. The interface mechanism comprises pneumatically or electromechanically driven actuators for engaging support elements in the instrument to components on the cartridge. After the cartridge has been securely received by the interface mechanism, the connection sequence is initiated. The interface provides separate high voltage and optical connections for each separation channel in the cartridge, thus providing channel-to-channel isolation from cross talk both electrically and optically.

Abstract: A lens-coupled camera for an electron microscope is disclosed. The camera includes a CCD, a scintillator, at least one lens, and a mirror, such that at least the CCD and scintillator are housed in the vacuum chamber of the electron microscope, which has only one vacuum chamber. In a further embodiment, the CCD, scintillator, lens and mirror are affixed to a fixed mechanical linkage such that the CCD, scintillator, lens and mirror move together when the camera is retracted.

Abstract: Methods are disclosed for operating a device having a high energy particle detector wherein the particles create first incoming traversal events, outgoing backscatter events, higher-order in and out events and incoming events caused by particles which backscatter out of the device, hit nearby mechanical structures and are scattered back into the device. Exemplary method steps include discriminating incoming traversal events from outgoing backscatter events, higher-order in and out events and incoming events by limiting dose rate to a level at ensures that separate events do not overlap and discriminating events from background and from other events based on total energy in each event; discriminating backscatter events from incoming traversal events based on electron path shape; or determining that a first event and a second event are coincident with each other and separating incoming form backscatter events based on electron path shape and energy level.

Abstract: An apparatus for aligning a capillary column with one or more excitation fibers and with one or more optical lens elements for Capillary Electrophoresis. The apparatus includes two identical blocks having a plurality of grooves for positioning and aligning the capillary column with the one or more excitation fibers, and a plurality of lens seats for optically coupling the lens element with the capillary column. Each block includes a male and female part for mating the two identical blocks together.

Abstract: The present invention provides for an interface mechanism in a bio-separation instrument that makes interface connections to a multi-channel cartridge. The interface mechanism precisely positions the cartridge in relation to the support elements in the instrument (e.g., high-voltage, gas pressure, incident radiation and detector), and makes automated, reliable and secured alignments and connections between various components in the cartridge and the support elements in the supporting instrument. The interface mechanism comprises pneumatically or electromechanically driven actuators for engaging support elements in the instrument to components on the cartridge. After the cartridge has been securely received by the interface mechanism, the connection sequence is initiated. The interface provides separate high voltage and optical connections for each separation channel in the cartridge, thus providing channel-to-channel isolation from cross talk both electrically and optically.

Abstract: A simplification of the charge-collection pixel of an imaging detector for high-energy electrons is disclosed, incorporating removal of the buffer amplifier. While sacrificing speed and noise performance of the readout somewhat and therefore appearing counter-intuitive, this configuration has the potential to significantly reduce the susceptibility of the pixel to radiation damage.

Abstract: A method is disclosed for acquiring an image in a sensor having a substrate side and a front side comprising illuminating the semiconductor image sensor with electrons that approach the sensor from the substrate side.

Abstract: An apparatus for aligning a capillary column with one or more excitation fibers and with one or more optical lens elements for Capillary Electrophoresis. The apparatus includes two identical blocks having a plurality of grooves for positioning and aligning the capillary column with the one or more excitation fibers, and a plurality of lens seats for optically coupling the lens element with the capillary column. Each block includes a male and female part for mating the two identical blocks together.