Microfluidic intact cell platform: A novel tool for oral cancer detection

微流控完整细胞平台：口腔癌检测的新工具

• 批准号: 10043470
• 负责人: Umut A. Gurkan
• 金额: $ 41.4万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043470
• 关键词: Address; Aliquot; Bedside Testings; Benign; Biological; Biological Assay; Biological Markers; Biopsy; Caliber; Cancer Detection; Cancerous; Carcinoma in Situ; Cations; Cell membrane; Cells; Cellular Assay; Cellular Phone; Clinical Research; Coin; Collaborations; Collecting Cell; Computational algorithm; Computer Analysis; Consumption; Contralateral; Country; Custom; Dental Clinics; Detection; Developing Countries; Development; Devices; Diagnosis; Early Diagnosis; Early Intervention; Engineering; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Event; Expression Profiling; Fluorescence; Fluorescent Antibody Technique; Future; Goals; Gold; Head and Neck Cancer; Health care facility; Histopathology; Hour; Human; Image; Immobilization; India; Indigenous; Individual; Label; Laboratories; Lesion; Measures; Medicine; Methods; Microfluidic Microchips; Microfluidics; Molecular; Monitor; Mouth Carcinoma; Myelogenous; Non-Invasive Lesion; Observational Study; Oral; Oral Stage; Oral cavity; Oral mucous membrane structure; Pain; Pathology; Patient-Focused Outcomes; Patients; Peptides; Phase; Phenotype; Primary Health Care; Procedures; Proteins; Reporting; Research Personnel; Resources; Sampling; Screening for Oral Cancer; Screening procedure; Site; Specificity; Swab; System; Techniques; Technology; Testing; Time; Tissues; University Hospitals; Work; antimicrobial; antimicrobial peptide; base; beta pleated sheet; beta-Defensins; beta-defensin 3; biomarker development; cellular imaging; chemokine; clinical care; cost; cost effective; deep learning algorithm; diagnosis standard; diagnostic accuracy; experience; fluorescence imaging; imaging Segmentation; imaging capabilities; imaging platform; immunoregulation; improved; improved outcome; indexing; innovation; malignant mouth neoplasm; metaplastic cell transformation; microfluidic technology; monitoring device; mouth squamous cell carcinoma; mucosal site; novel; novel strategies; oral lesion; overexpression; patient population; point of care; portability; portable monitoring; premalignant; primary care setting; prospective; prototype; recruit; scalpel; screening; socioeconomics; success; tertiary care; tool

Oral squamous cell carcinoma (OSCC) claims the lives of thousands in the U.S. and hundreds of thousands worldwide annually. A biopsy followed by histopathology, the gold standard for the diagnosis of OSCC, is painful, invasive, costly, not practical if longitudinal assessments of the same lesion are required and oftentimes is not available or imprecise in third world countries. A tool that quickly distinguishes cancerous from non- cancerous lesions and identifies progressive or transforming lesions could allow for early intervention, which would improve outcomes and negate the need for unnecessary biopsies in patients whose lesions remain benign or haven’t begun to degenerate. Therefore, there is an unmet need for a rapid, non-invasive, objective and cost-effective test for OSCC. We and others have reported that an altered expression profile of human beta defensin 3 (hBD-3), an epithelial cell derived antimicrobial peptide (AMP), and hBD-2, another epithelial cell AMP, is an early event in OSCC. Therefore, the ratio of hBD-3 and hBD-2 in the lesion, when compared to the contralateral site, could be exploited in distinguishing OSCC from other lesions of the oral cavity. We refer to this ratio as the beta defensin index (BDI). Our ongoing clinical study of 78 subjects with suspicious oral lesions demonstrated high sensitivity (100%) and specificity (74%) of the ELISA based BDI in distinguishing cancerous from noncancerous oral lesions (P<0.0001). With the high accuracy (98%) of our BDI based molecular assay, we now wish to advance our novel platform from the laborious, time consuming ELISA format into an imaging-based point-of-care (POC) device that utilizes microfluidic technology to quantify the BDI with an expected turnover time of half an hour. Our microfluidic intact cell assay (MICA) approach to developing a POC device for oral cancer detection is unique; it utilizes intact epithelial cells trapped in a microfluidic chip encompassing microfabricated pillar arrays with varying spaces to allow the capture of epithelial cells. Upon capture, the cells are permeabilized and labeled with fluorescent antibodies for hBD ratio analysis. We employ automated fluorescence imaging and computational algorithm to enable automated calculation of the BDI scores. We now hypothesize that the ELISA format that can effectively detect oral cancer, can be configured for point of care MICA, retaining its high accuracy and making it easier to use worldwide. To advance the discovery of this new approach for oral cancer detection, we propose the following aims: 1. Develop a working prototype of a MICA POC device for oral cancer testing equipped with cell imaging and BDI calculation capabilities. 2. Conduct a discovery phase study where MICA POC and ELISA, as independent assays, will be compared with pathology review in their ability to detect oral cancer. The MICA POC, while not intending to replace biopsy, could be deployed, in the future, to objectively and non- invasively determine who actually needs a biopsy, monitor oral premalignant lesions in real world practice and fulfill a major unmet need in low-socio economic countries where pathology review is lacking and/or unreliable.

口腔鳞状细胞癌（OSCC）在美国夺去了成千上万人的生命

项目成果

Integrating pathomics with radiomics and genomics for cancer prognosis: A brief review.

• DOI: 10.21147/j.issn.1000-9604.2021.05.03
• 发表时间: 2021-10-31
• 期刊: Chinese journal of cancer research = Chung-kuo yen cheng yen chiu
• 作者: Lu C;Shiradkar R;Liu Z
• 通讯作者: Liu Z

HBD-2 binds SARS-CoV-2 RBD and blocks viral entry: Strategy to combat COVID-19.

• DOI: 10.1016/j.isci.2022.103856
• 发表时间: 2022-03-18
• 期刊: iScience
• 影响因子: 5.8
• 作者: Zhang L;Ghosh SK;Basavarajappa SC;Chen Y;Shrestha P;Penfield J;Brewer A;Ramakrishnan P;Buck M;Weinberg A
• 通讯作者: Weinberg A

Feature-driven local cell graph (FLocK): New computational pathology-based descriptors for prognosis of lung cancer and HPV status of oropharyngeal cancers.

特征驱动的局部细胞图（FLOCK）：用于肺癌预后和口咽癌的HPV状态的新的基于计算病理学的描述。

• DOI: 10.1016/j.media.2020.101903
• 发表时间: 2021-03
• 期刊: Medical image analysis
• 影响因子: 10.9
• 作者: Lu C;Koyuncu C;Corredor G;Prasanna P;Leo P;Wang X;Janowczyk A;Bera K;Lewis J Jr;Velcheti V;Madabhushi A
• 通讯作者: Madabhushi A

An unsupervised method for histological image segmentation based on tissue cluster level graph cut.

一种基于组织簇级图割的无监督组织学图像分割方法。

• DOI: 10.1016/j.compmedimag.2021.101974
• 发表时间: 2021
• 期刊: Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society
• 作者: Xu,Hongming;Liu,Lina;Lei,Xiujuan;Mandal,Mrinal;Lu,Cheng
• 通讯作者: Lu,Cheng