Devices and methods to image objects by time delay integration

Abstract

Devices and methods for automated collection and image analysis are disclosed that enable identification or classification of microscopic objects aligned or deposited on surfaces. Such objects, e.g. detectably labeled rare target cells, are magnetically or non-magnetically immobilized and subjected to Time Delay Integration imaging (TDI). Incorporation of TDI technology into image cytometry analysis, like CellTracks®, makes it possible to image moving objects with very high sensitivity and signal-to-noise ratios. Implementation of TDI camera technology with dual excitation and multispectral imaging of enriched rare cells provides a rapid system for detection, enumeration, differentiation and characterization of imaged rare cells on the basis of size, morphology and immunophenotype.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. application Ser. No. 10 / 612,144, and U.S. Provisional Application No. 60 / 494,101, filed 11 Aug. 2003, under 35 U.S.C. section 119 (e). The entire disclosure of which is incorporated by reference herein.TECHNICAL FIELD [0002] This invention relates generally to devices and methods to obtain to scan and obtain images of objects, and more particularly to images reconstructed from partial sub-images of object such as cells obtained from biological fluids that are distributed in a two-dimensional plane. The scanning and imaging technique provided by the invention is especially advantageous for the imaging of cells that are aligned by magnetic means and examined by digitized optoelectronic means through Time-Delay-Integration. BACKGROUND OF THE INVENTION [0003] The identification and enumeration of circulating carcinoma cells of epithelial origin in the blood of cancer patients that may be present at f...

AI Technical Summary

Benefits of technology

The invention is a system and method for detecting, classifying, and enumerating cells using magnetically labeled target cells and automated imaging analysis. The system includes a system for collecting and aligning cells, as well as a laser scanning system for detecting fluorescence emissions. The invention allows for efficient detection of rare cells, with minimal sample handling and increased sensitivity. The system can also be integrated into existing imaging systems for further analysis. Overall, the invention provides a powerful tool for the detection of rare events in body fluids.

Problems solved by technology

However, morphometric confirmations of the detected events as cells and further molecular evidence is lacking in flow cytometric methods, but is clearly needed to assure that the detected rare events are indeed tumor cells derived from a primary tumor.

Automated image analysis systems have been introduced to reduce subjective errors in cell classification between different operators in manual methods, but such prior art systems without preliminary cell enrichment steps still inherently lack sensitivity.

However, these and other currently available methodologies are not sufficiently sensitive for accurate classification and typing of rare events such as circulating tumor cells in blood.

The disadvantage is that when scanning, the laser is only illuminating a small area of the cell.

Another disadvantage of this type of imaging is that a full frame camera is not collecting photons during readout of the CCD.

Consequently, all fluorescent photons emitted at that moment are useless.

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