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.
The US-FFPE tissue specimen preparation technology can reduce the whole tissue specimen preparation time from 16-48 hr to less than 1 hr, thus it can greatly shorten the turn-around time of cancer diagnosis and makes it possible for standardization of clinical tissue specimen preparation. To achieve the potential of the US-FFPE technology in clinical application, we will greatly enhance the prototype device developed under Phase I. A systemic study with all clinically relevant tissue samples will be performed to validate the newly developed device and to establish a database of optimal operation conditions.