SBIR-STTR Award

This project will generate the detailed design for an advanced hematology instrument and specimen preparation system capable of expanding clinical hematology testing. Specifically, a prototype automated imaging microspectrophotometer, and improved methods for clinical and research testing of blood cells based on direct hemoglobin absorbance for erythrocytes and a specific fluorochrome and monoclonal antibody immunofluorescence for leukocytes will be developed. The instrument will measure fluorescence or absorbance at multiple specific wavelengths in each pixel in high-resolution images of cells using a CCD (charge-coupled device) imager and high-speed monochromators. Image analysis will be based on the spectral properties of each image pixel, from which spatial and integrated parameters can be formed for each cell.The prototype will be used to develop designs for each component of the production version of the instrument system until the software and hardware designs are completed. This system is innovative in its optical and non-optical hardware designs, specimen preparation methods, and image processing strategies, and should contribute significantly in clinical and research hematology, oncology, and cellular immunology.National Heart, Lung, and Blood Institute (NHLBI)

Phase I will explore, via computer simulation, in a very high-speed computer the use of state-of-the-art RCA Charge Coupled Devices (CCD) in an Automated Diagnostic Microscope (ADM) for imaging and analyzing blood cells stained with a quantitative fluorescent technique that allows accurate characterization of all of the types of cells encountered in periferal blood. Digital images prepared from calibrated microphotographs of white blood cells, platelets, and red cells, will be used to represent the output of the CCD imagers in the computer simulation. The simulation will then be used to design the prototype instrument. Phase I will also include the structuring of the simulated image data into parameters related to the quantity and morphology of cell constituents (DNA, nuclear size and shape, heterochromatin, cytoplasmic volume and shape, hemoglobin, specific granules, lysosomes, and RNA). Software will then be developed and explored for using these parameters to classify and describe blood cells. The parameters will then be used to guide the development of cell analysis software. The technique of computer simulation should very significantly aid in speedy production of a functioning prototype ADM in Phase II. The ADM will represent a significant advance in blood cell imaging because of its high resolution and sensitivity that capitalize on a quantitatively interpretable specimen. The ADM will expand the data base describing normal and abnormal (including neoplastic) blood and bone marrow cells, providing quantitative diagnostic parameters that are not currently available. The first level design goal is, however, to provide all of the currently available hematologic tests made on blood cells in a completely automated mode. The ADM will be extremely cost-effective. It will perform all the tests done on blood cells in the clinical hematology laboratory at least as fast and in more detail than current instrumentation. The ADM will be capable of the diagnostic discrimination of blood cells, and will be easily adapted to the utilization of monoclonal antibodies in cell identification and characterization. These factors should stimulate commercial interest.

Thesaurus Terms:
Biomedical engineering, instrumentation not clinically oriented, biomedical systems automated, blood (hematologic) tests, blood cells, chemistry, analytical methods, spectrometry, microspectrophotometry, molecular cytology study section, computer simulation biomedical systems automated, computer assisted diagnosis, blood (hematologic) tests, bone marrow examination, diagnostic quality-standards, diagnostic tests, rapid diagnosis, immunological preparations, monoclonal antibodies, optics, image processing analysis and display, tissue and cell preparation, staining, computer programming