Systems and methods for detecting target focus and tilt errors during genetic analysis
First Claim
1. A system for interrogating a sample using a probe array configured to be responsive to a plurality of particles wherein the probe array generates one or more identifiable signals following interaction with the sample particles and wherein the sample composition is resolved, at least in part, by identifying the signals associated with each constituent probe of the array, the system comprising:
- an imaging device capable of identifying signals associated with the constituent probes of the probe array wherein the position of each constituent probe and the signal arising therefrom is used to identify the presence or absence of particles contained within the sample;
a focusing component that positions the imaging device and the probe array with respect to each other so as to obtain a desired focal orientation between the imaging device and the probe array;
a focus detection system that includes a plurality of detectors wherein the focus detection system directs a calibration beam towards the probe array which is reflected with an orientation dependent on the positioning of the array and wherein the calibration beam is subsequently split into a plurality of reflected beams which impinge upon the plurality of detectors such that the plurality of detectors detect the impingement positions of the plurality of reflected beams in at least two dimensions and wherein the focus detection system uses the at least two dimensional impingement positions to determine how to move the image capture device and the probe array with respect to each other in order to position the imaging device and the probe array in the desired focal orientation; and
a processing system that evaluates signals captured by the imaging device when the probe array and the imaging device are in a desired focal orientation.
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Accused Products
Abstract
Systems and methods for positioning a camera target relative to a signal acquisition frame. Detection of the target'"'"'s position deviation may be achieved by a calibration beam being reflected from the target surface and being detected by at least two position sensitive detectors (PSDs) to thereby allow removal of ambiguity in the target'"'"'s Z-focus error from its tilt error. The PSD-measured quantities can be transformed into target control space quantities that can be used in a control loop to reduce the target position error. The calibration beam and one or more of the PSDs can also be used to detect the target'"'"'s edges, thereby allowing lateral centering of the target relative to the reference frame.
27 Citations
46 Claims
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1. A system for interrogating a sample using a probe array configured to be responsive to a plurality of particles wherein the probe array generates one or more identifiable signals following interaction with the sample particles and wherein the sample composition is resolved, at least in part, by identifying the signals associated with each constituent probe of the array, the system comprising:
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an imaging device capable of identifying signals associated with the constituent probes of the probe array wherein the position of each constituent probe and the signal arising therefrom is used to identify the presence or absence of particles contained within the sample;
a focusing component that positions the imaging device and the probe array with respect to each other so as to obtain a desired focal orientation between the imaging device and the probe array;
a focus detection system that includes a plurality of detectors wherein the focus detection system directs a calibration beam towards the probe array which is reflected with an orientation dependent on the positioning of the array and wherein the calibration beam is subsequently split into a plurality of reflected beams which impinge upon the plurality of detectors such that the plurality of detectors detect the impingement positions of the plurality of reflected beams in at least two dimensions and wherein the focus detection system uses the at least two dimensional impingement positions to determine how to move the image capture device and the probe array with respect to each other in order to position the imaging device and the probe array in the desired focal orientation; and
a processing system that evaluates signals captured by the imaging device when the probe array and the imaging device are in a desired focal orientation. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. An optical system comprising:
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an analysis platform comprising a sample disposed on a probe array wherein each probe is configured to be responsive to a specific particle and wherein when the probe array is exposed to the sample, the probes generate identifiable signals based on the interaction of the probes with specific particles within the sample;
an image capture device that captures an image of the probe array so as to be able to identify the position of the signal generating probes to thereby identify the composition of specific particles contained within the sample;
a focusing component that positions the image capture device and the analysis platform with respect to each other so as to obtain a desired focal orientation between the image capture device and the analysis platform;
a focus detection system that includes a calibration data set and a plurality of detectors wherein the focus detection system directs an energy beam towards the array of probes which is then reflected with an orientation dependent on the positioning of the array and wherein the reflected energy beam is split into a plurality of reflected beams which impinge upon the plurality of detectors such that the plurality of detectors detect the impingement positions of the plurality of reflected beams in at least two dimensions and wherein the focus detection system uses the at least two dimensional impingement positions and the calibration data to determine how the focusing component must relatively move the image capture device and the analysis platform with respect to each other in order to relatively position the image capture device and the analysis platform in the desired focal orientation; and
a processing system that evaluates the image captured by the image capture device when the analysis platform and the image capture device are in the desired focal orientation wherein the desired focal orientation is selected to improve the ability of the processing system to determine the physical location on the array of probes of the generated signals to thereby permit identification of the particle composition in the sample based upon the location of signals detected in the probe array. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
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29. A system for interrogating a sample via an array of probes positioned on an analysis platform wherein each probe is configured to be responsive to a specific particle having unique identifying characteristics and wherein when the array of probes is exposed to the sample, the probes generate an identifiable signal based on the interaction of the probes with specific particles within the sample based upon the unique identifying characteristics of the specific particle, the system comprising:
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an image capture device that captures a two dimensional image of the array of probes so as to be able to identify the position of the signal generating probes to thereby identify the composition of specific particles contained within the sample;
a focusing component that positions the image capture device and the analysis platform with respect to each other so as to obtain a desired focal orientation between the image capture device and the analysis platform;
a focus detection system that includes a calibration data set and a plurality of detectors wherein the focus detection system directs an energy beam towards the array of probes which is then reflected with an orientation dependent on the positioning of the array and wherein the reflected energy beam is split into a plurality of reflected beams which impinge upon the plurality of detectors such that the plurality of detectors detect the impingement positions of the plurality of reflected beams in at least two dimensions and wherein the focus detection system uses the at least two dimensional impingement positions and the calibration data to determine how the focusing component must relatively move the image capture device and the analysis platform with respect to each other in order to relatively position the image capture device and the analysis platform in the desired focal orientation; and
a processing system that evaluates the image captured by the image capture device when the analysis platform and the image capture device are in the desired focal orientation wherein the desired focal orientation is selected to improve the ability of the processing system to determine the physical location on the array of probes of the generated signals to thereby permit identification of the particle composition in the sample based upon the location of signals detected in the array.
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30. A method for obtaining a selected focal orientation between an imaging device and a probe array to resolve signals corresponding to a plurality of discrete probe species, the method comprising:
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directing a calibration beam towards the probe array in such a manner so as to produce a reflected calibration beam having an orientation dependent, in part, upon the positioning of the probe array;
splitting the reflected calibration beam into two or more reflected beams which subsequently impinge upon two or more beam detectors wherein the beam detectors detect the impingement positions of the two or more reflected beams in at least two dimensions;
evaluating the impingement positions of the two or more reflected beams to determine the current positioning between the imaging device and the probe array;
calculating positional adjustments necessary to position the imaging device and the probe array with respect to each other in the selected focal orientation; and
repositioning the imaging device and the probe array according to the calculated positional adjustments to achieve the selected focal orientation. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
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44. A method for determining a focal orientation between an imaging device and a target, the method comprising:
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directing a calibration beam towards the target in such a manner so as to produce a reflected calibration beam having an orientation dependent, in part, upon the positioning of the target;
splitting the reflected calibration beam into two or more reflected beams which subsequently impinge upon two or more beam detectors wherein the beam detectors detect the impingement positions of the two or more reflected beams in at least two dimensions; and
evaluating the impingement positions of the two or more reflected beams to determine the current positioning between the imaging device and the target. - View Dependent Claims (45, 46)
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Specification