Image analysis – Applications – Biomedical applications
Reexamination Certificate
2002-09-30
2003-07-08
Johns, Andrew W. (Department: 2621)
Image analysis
Applications
Biomedical applications
Reexamination Certificate
active
06591003
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to optical tomographic imaging systems in general, and, more particularly, optical tomography where objects are imaged using optical tomography and time delay and integration.
BACKGROUND OF THE INVENTION
U.S. application Ser. No. 10/126,026 of Alan Nelson, filed Apr. 19, 2002, entitled “VARIABLE-MOTION OPTICAL TOMOGRAPHY OF SMALL OBJECTS” is incorporated herein by this reference. In Nelson, projection images of shadowgrams are digitally captured by means of conventional CCD or CMOS image detectors. In imaging moving objects, such image sensors require short exposures to “stop motion” in order to reduce motion blur. Short exposures limit the signal to noise ratio that can be attained when imaging moving objects.
It is advantageous in optical tomography (OT) to image moving objects such as in a flow stream or entrained in a rigid medium for high throughput analysis. Additionally, in the case of objects entrained in a rigid medium, design of the presentation stage or sample positioner is simpler for constant velocity motion than for rapid stop and go motion. Moreover, in such a system, constant motion produces less vibration than stop and go motion.
Generally, time delay and integration (TDI) imaging is based on the concept of accumulating multiple exposures of the same moving object, thereby effectively increasing the integration time available to collect incident light. The object motion must be synchronized with the exposures to ensure a crisp image. Typically, TDI detectors include pixels arranged in rows and columns. An electronic signal is moved from row to row in synchrony with a moving image projected onto the device. The synchronized signal results in an extended integration time without blurring.
U.S. Pat. No. 6,249,341 to Basiji, et al. issued Jun. 19, 2001 entitled “Imaging and Analyzing Parameters of Small Moving Objects Such as Cells,” discloses an apparatus where light from an object such as a cell moving through an imaging system is collected and dispersed so that it can be imaged onto a time delay and integration (TDI) detector. Basiji, et al. define a TDI detector as any pixellated device in which the signal produced in response to radiation directed at the device can be caused to move in a controlled fashion. Basiji, et al. does not address optical tomography, a deficiency overcome by the present invention.
SUMMARY OF THE INVENTION
The present invention provides an apparatus and method for three dimensional (3D) reconstruction of an object of interest moving at a constant velocity. The object of interest is centered. The object of interest is imaged with optical point sources located at multiple projection angles around the object of interest, in cooperation with opposing time delay and integration (TDI) image sensors located at a distance from the objects of interest such that there is no focal plane within the objects of interest during imaging. Each of the TDI sensors has a line transfer rate synchronized to the constant velocity of the objects of interest.
In one aspect, the present invention provides a method for three dimensional (3D) reconstruction of objects of interest in a laminar flow stream. Objects of interest are injected into a laminar flow stream such that objects are centered in the laminar flow stream and moving at a constant velocity. The objects of interest are sampled with at least one optical point source located around the laminar flow stream, in cooperation with at least one opposing time delay and integration (TDI) image sensor located opposite the at least one optical point source at a distance from the laminar flow stream such that there is no focal plane within the objects of interest during sampling. Multiple projection angles through objects of interest are sampled as they flow between the at least one optical point source and at least one opposing TDI image sensor. At least one projection image is generated with the TDI image sensor, the line transfer rate of which is synchronized to the flow rate of the objects of interest.
In another aspect, the present invention overcomes deficiencies in the prior art by providing a method and system for three dimensional optical tomography using photon point source or parallel beam projections and time delay and integration (TDI) image sensors. More particularly, a system is provided for imaging microscopic objects, including biological cells, in a flow stream or entrained in a rigid medium using optical tomography.
It is a motivation of this invention to improve signal to noise ratio of projection images in dynamic optical tomography systems by taking advantage of the ability of TDI image sensors to track moving objects.
In another aspect the present invention takes advantage of the ability of TDI image sensors to track objects moving in the direction of charge transfer on the sensor and synchronized to the sensor's line transfer rate. In one embodiment, the present invention provides a method of capturing or digitizing projection images or shadowgrams in an optical tomography instrument with a time delay and integration (TDI) image sensor oriented such that the line transfer vector is parallel to the motion vector of the cells as they are presented to the reconstruction cylinder by either a laminar flow stream or mechanically translated under computer control.
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Chu Chee-Wui
Nelson Alan C.
Johns Andrew W.
Leone George A.
Nakhjavan Shervin
Visiongate, Inc.
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