Recently advances in imaging biological cells using optical tomography invented by A. C. Nelson have been disclosed, for example, in U.S. Pat. No. 6,522,775, issued Feb. 18, 2003, and entitled “Apparatus And Method For Imaging Small Objects In A Flow Stream Using Optical Tomography,” the full disclosure of which is incorporated by reference. Further developments in the field are taught in Fauver et al., U.S. Pat. No. 7,738,945 issued on Jun. 15, 2010, entitled “Method And Apparatus Of Shadowgram Formation For Optical Tomography,” and Fauver et al., U.S. Pat. No. 7,907,765, issued on Mar. 15, 2011, entitled “Focal Plane Tracking For Optical Microtomography,” the full disclosures of which are also incorporated by reference.
Processing in such an optical tomography system begins with specimen preparation. Typically, specimens taken from a patient are received from a hospital or clinic and processed to remove non-diagnostic elements, fixed and then stained. Stained specimens are then mixed with an optical fluid, inserted into a micro-capillary tube and images of objects, such as cells, in the specimen are produced using an optical tomography system. The resultant images comprise a set of extended depth of field images from differing perspectives called “pseudo-projection images.” The set of pseudo-projection images can be reconstructed using backprojection and filtering techniques to yield a 3D reconstruction of a cell of interest.
The 3D reconstruction then remains available for analysis in order to enable the quantification and the determination of the location of structures, molecules or molecular probes of interest. An object such as a biological cell may be labeled with a stain or tagged molecular probe, and the measured amount and location of this probe may yield important information about the disease state of the cell, including, but not limited to, various cancers such as lung, breast, prostate, cervical and ovarian cancers.
In one type of optical tomography system, as described in U.S. Pat. No. 7,738,945 and constructed by VisionGate, Inc., the depth of field of the imaging optics is extended by scanning an objective lens transverse to a capillary tube containing a specimen. A piezoelectric transducer (PZT) actuator moves the objective lens sinusoidally several times per second in order to scan a series of focal planes though a specimen. By using a PZT actuator to move the objective lens, a focal plane moving through the specimen has its speed limited by inertia inherent in moving the objective lens rapidly along the optical axis through the specimen. Because the objective lens is housed in a relatively massive assembly, the scan rate is typically, about 10 Hz with a theoretical upper limit of roughly 60 cycles per second. During each scan an image sensor acquires at least one pseudo-projection image. With well-synchronized rotation and objective scanning, an image can be acquired on the down-stroke as well as the up-stroke of the PZT actuator, allowing up to 120 images per second to be acquired. While this is a useful acquisition rate, it can be significantly improved through the apparatus, systems and methods disclosed herein.
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