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Low-Cost CRISPR-on-Paper for Cervical Cancer Screening at the Point of Care

用于宫颈癌护理点筛查的低成本纸上 CRISPR

基本信息

批准号：
10611463
负责人：
Changchun Liu
金额：
$ 52.06万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10611463
关键词：
Acetic Acids Address Air Bioinformatics Biological Assay COVID-19 detection Cancer Etiology Cellular Phone Cervical Cancer Screening Cessation of life Chemicals Clinical Clinical Sensitivity Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Complex Cytology DNA Data Detection Devices Electronics Engineering Equipment Eye Feedback Funding Genotype HPV-High Risk Hand Health Health Personnel Human Papillomavirus Human papilloma virus infection Image Infectious Diseases Research Interdisciplinary Study Laboratories Lesion Malignant neoplasm of cervix uteri Methods Microfluidic Microchips Microfluidics Molecular Nucleic Acids Oncologist Optics Paper Performance Polymerase Chain Reaction Printing Procedures Process Published Comment RNA Reaction Recommendation Reporting Reproducibility Resource-limited setting Resources Sampling Sensitivity and Specificity Services Specificity Speed Swab System Technology Temperature Test Result Testing Time Training United States Food and Drug Administration Virus Visual Waxes Woman World Health Organization Zambia anticancer research burden of illness chronic infection clinical application cost design detection assay detection method detection sensitivity detector diagnostic platform emerging pathogen experience global health health training high risk industry partner innovation instrument internal control low and middle-income countries multiplex detection novel point of care point-of-care diagnostics portability rapid technique smartphone application technology platform

项目摘要

Abstract Cervical cancer is among the leading causes of cancer death in women worldwide, especially in low- and middle- income countries (LMICs). High-risk human papillomaviruses (HPV) are the main causative agents of cervical cancer and its precursor lesions; therefore, the World Health Organization (WHO) has recommended HPV DNA testing for cervical cancer screening in LMICs. Although polymerase chain reaction (PCR) methods have been widely used for HPV DNA detection, they are restricted to centralized clinical laboratories due to the need for labor-intensive procedures and expensive equipment. Here, we propose to develop a simple, rapid, highly sensitive, and specific CRISPR-on-paper diagnostic platform to simultaneously detect multiple high-risk HPV genotypes for cervical cancer screening at the point of care. This innovative diagnostic system is based on our recently developed all-in-one dual CRISPR-Cas12a (AIOD-CRISPR) assay, which combines the simplicity and high sensitivity of isothermal nucleic acid amplification with the high specificity of CRISPR detection. To develop a low-cost, multiplexed molecular detection technology, we will incorporate the AIOD-CRISPR assay into a paper-based microfluidics platform. To eliminate the need for complex electronic instruments, we will take advantage of an exothermic reaction to generate chemical heat for the CRISPR-on-paper system by using a disposable hand warmer, thus enabling instrument-free cervical cancer screening. The detection results can be read by the naked eye or reported by a programmed smartphone without the need for an expensive optical detector. We will rigorously evaluate and validate the clinical applications of our CRISPR-on-paper diagnostic system by testing clinical samples in collaboration with clinicians and healthcare workers in UConn Health and Zambia. If successful, the proposed project has an important impact on global health by providing a simple, affordable, and sensitive method for rapid screening of cervical cancer in resource-poor settings. As a platform technology, the proposed CRISPR-on-paper diagnostic system can be easily adapted to detect other emerging pathogens.

摘要