SBIR-STTR Award

The primary goal of Bio-Quick is to provide a vehicle to transform the innovative biotechnology available in research labs from Armed Forces Institute of Pathology into marketable and profitable medical instruments that can greatly benefit the health care, food market safety control, and the advancement in medical community. Formalin-fixation and paraffin-embedding (FFPE) is a time-consuming but standard tissue preservation and processing method used in over 90 percent cases in hospitals and clinical settings for routine histology diagnosis. Our proposed project is to design and develop an ultrasound-facilitated processor (DTP) for rapid tissue fixation and processing for histology diagnosis and any further molecular study if necessary. The implementation of the technique will allow a significant reduction in processing time from at least 24 hours by conventional FFPE to less than 1 hour. We also need funding to support collaboration with outside and independent researchers to provide objective evaluation of the technique. Our specific aims of this SBIR phase I project are: 1) Development of a commercialized intensity adjustable bench top fixer/processor for rapid formalin fixation and paraffin embedding, 2) Evaluate and validate the DTP method in comparison to conventional FFPE method based on preservation of morphological details and molecular analyses. During the past 7 years, we have compared the DTP method with conventional FFPE method on over 100 human tissue specimens of 14 tissue types. Our preliminary data have demonstrated that compared to conventional FFPE, US-facilitated FFPE not only significantly reduces the total fixation/processing time from over 24 hours to within 1 hour, but also preserves similar or better tissue morphology, much improved protein antigen properties and mRNA integrity. As a results of improved preservation of macromolecules, antigen retrieval treatment prior to IHC staining may be reduced, much reduced (20X or more) antibody concentration and shortened IHC reaction time are used. Long-term stability of tissue morphology and mRNA integrity in USFFPE tissues is slightly better than that in conventional FFPE tissues

Ultrasound (US) facilitated formalin-fixed and paraffin-embedded (FFPE) tissue specimen preparation technology (US-FFPE) is developed from the widely accepted FFPE technology by introducing ultrasound in every step of the process. The US-FFPE does not change the gold standard FFPE tissue morphology. However, it greatly reduces tissue specimen preparation time. The whole procedure of FFPE tissue specimen preparation is reduced from 16-48 hr to 20-60 min. The final diagnosis of cancers can be produced in a few hours after surgery or biopsy instead of a few days. This increase of turnaround rate will considerably save patient care costs and greatly relieve patients' psychological burdens in waiting for results. Besides accelerating reagent penetration into tissues, the US-FFPE technology changes the mechanism of biomolecule modification and cross-linking caused by formalin fixation. Biomolecules are much more accessible for detection and extraction. The fact that tissue specimens are ""frozen in time"" at the point of US-FFPE fixation can greatly improve the integrity of biomolecules in tissue specimens, especially for mRNA and phosphoproteins. The Phase I of this project is highly successful. We have constructed a prototype US-FFPE device with continuous-flow and multi-sample capacity. Morphological and molecular biology assay results on tissue specimens produced by the prototype US-FFPE device were highly comparable or even superior to those on tissue specimens produced by the conventional FFPE method. Our goal of the Phase II project is to construct a prototype US-FFPE device that can be applied in clinical tissue specimen preparation to produce standardized tissue specimens at much increased turnaround rate. Different from the conventional FFPE method, the US-FFPE method relies on US to increase speed. With much shortened sample processing time, strict control of the machine performance parameters is critical. Under Phase II, we will develop a highly reliable US-FFPE device with real-time quality control and quality assurance (QC/QA) system. The Phase II objectives are: 1) to improve the prototype Phase I US-FFPE device by optimizing the existing functions to achieve high device reliability as well as by addition of new functions to achieve QC/QA; 2) to perform systemic morphological and molecular studies with various tissue types to validate the device and to collect optimal machine operating parameters.

Thesaurus Terms:
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