STTR Phase I: An automated digital pathology lab for rapid on-site processing and imaging of tissue biopsies

该STTR第1阶段项目旨在开发一种自动化系统，该系统将显著提高护理点活检评估的速度和准确性。所提出的技术消除了大量的手动组织处理步骤，并生成看起来就像标准病理切片的新鲜活检的数字图像。成像可以在几秒钟内完成，从而提高了现场活检评估的效率。快速、全新的活检成像还可以提高评估准确性，同时最大限度地保留组织以供进一步测试，并促进远程病理咨询。美国每年有超过500万患者接受活检手术，其中五分之一的患者因活检评估不准确而返回重复手术，准确性和手术速度的提高可能会产生深远的影响。这可能导致患者手术时间缩短，重复手术率降低，防止不必要的、痛苦的和侵入性的重复活检手术。据估计，每年重复手术的费用为16亿美元，这也将大大减轻患者的经济负担。此外，由于每个程序的时间减少，这可以增加医院的程序吞吐量，从而增加医院的收入潜力。最后，通过产生远程可视图像，该系统可以在美国服务不足的社区的远程病理设置中使用。该STTR第一阶段项目旨在开发一种自动化样本处理和组织病理成像系统，该系统可以在五分钟内以完全自动化的方式对完全完整的新鲜组织进行活检图像切除。 通过与先前开发的视频速率结构照明显微镜（VR-SIM）系统集成为集成光学切片模式，并使用新的荧光染料组合，概括了黄金标准组织学，活检评估的吞吐量，效率和准确性可以提高，同时最大限度地保留组织用于下游处理，并方便远程病理学咨询。在多个新鲜组织制备中的初步工作，包括芯针活检和整个手术切除，表明该技术和方法可以在短的临床相关时间内提供高图像质量和诊断准确性。将开发用于活检染色和成像的自动化一次性盒系统原型，以便轻松集成VR-SIM成像。使用偏振选通VR-SIM和新型浸没介质，将在最高光学切片功率下优化图像质量，使其与物理切片组织等效。ADPL工作流程测试、诊断图像质量验证以及与人体活检样本下游分析兼容性验证将完成。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This STTR Phase 1 project seeks to develop an automated system that would significantly increase the speed and accuracy of biopsy assessments at the point of care. The proposed technology eliminates extensive manual tissue processing steps and generates digital images of fresh biopsies that look just like standard pathology slides. The imaging can be performed in seconds, thus improving the efficiency of biopsy assessments at the point of care. Rapid, whole fresh biopsy imaging also improves evaluation accuracy while maximally preserving tissue for further testing and facilitating remote pathology consultation. With over five million patients in the United States undergoing biopsy procedures each year, and one in five of those patients returning for repeat procedures due to inaccuracies in biopsy assessments, an increase in accuracy and procedure speed could have a profound impact. This could lead to decreases in patient procedure time and decreases in repeat procedure rates, preventing unnecessary, painful, and invasive repeat biopsy procedures. With an estimated 1.6 billion USD spend on repeat procedures per year, this would also represent a significant decrease in financial burden on patients. In addition, due to the decrease in time per procedure, this could increase procedure throughput for hospitals, thus increasing hospital revenue potential. Finally, by producing remotely viewable images, this system could be utilized in a remote pathology setting at underserved communities within the US.This STTR Phase I project seeks to develop an automated sample processing and tissue pathology imaging system that delivers biopsy-to-image in a completely automated manner on fully-intact fresh tissues within five minutes of tissue removal. Through integration with the previously developed Video-Rate Structured Illumination Microscopy (VR-SIM) system as the integrated optical sectioning modality, and using novel fluorescence dye combinations that recapitulate gold-standard histology, the throughput, efficiency, and accuracy of biopsy evaluation can be improved while maximally preserving tissue for downstream processing and readily facilitating telepathology consultation. Preliminary work in multiple fresh tissue preparations, including core-needle biopsies and whole surgical resections, indicates that the technology and method can deliver high image quality and diagnostic accuracy in short, clinically-relevant timeframes. A prototype of an automated, disposable cartridge system for biopsy staining and imaging for effortless integration with VR-SIM imaging will be developed. Image quality will be optimized at the highest optical sectioning power to be equivalent to physically-sectioned tissues, using polarization-gated VR-SIM and novel immersion media. ADPL workflow testing, validation of diagnostic image quality, and verification of compatibility with downstream analysis in human biopsy samples will be completed.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.