Development of Ultrasound-facilitated Formalin-fixed and Paraffin-embedded Tissue

DESCRIPTION (provided by applicant): 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.