A Microfluidic System for POC Molecular Diagnosis of HPV in Oral Fluids

用于口腔液中 HPV 的 POC 分子诊断的微流体系统

• 批准号: 8974126
• 负责人: Dipankar Manna
• 金额: $ 22.5万
• 依托单位: LUCIGEN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-05 至 2017-09-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8974126
• 关键词: Acute; Anogenital cancer; Anogenital venereal warts; Bedside Testings; Benign; Biological Assay; Cervical; Chemistry; Clinical; Clinical Trials; Collaborations; Common wart; Complex; DNA; DNA Sequence; DNA amplification; Data; Dentists; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Equipment; Disease; Early Diagnosis; Early Intervention; Encapsulated; Engineering; Equipment; FDA approved; Focal Epithelial Hyperplasia; Future; Genes; Genetic Transcription; Genital system; Genomic DNA; Genotype; Goals; Gold; Health; Human; Human Papillomavirus; Human Resources; Human papilloma virus infection; Human papillomavirus 16; Infection; Infectious Agent; International; Intervention; Laboratories; Lead; Licensing; Liquid substance; Malignant - descriptor; Malignant Neoplasms; Marketing; Mediating; Membrane; Messenger RNA; Microfluidics; Molecular; Molecular Diagnosis; Molecular Diagnostic Testing; Morbidity - disease rate; Nucleic Acids; Oral; Oral cavity; Patients; Pennsylvania; Pharyngeal structure; Phase; Plastics; Point-of-Care Systems; Population; Positive Test Result; Preparation; Process; RNA; RNA Sequences; RNA amplification; Reagent; Reporting; Research Personnel; Saliva; Sampling; Sexually Transmitted Diseases; Side; Site; Small Business Technology Transfer Research; Specificity; Squamous Cell Papillomas; Staging; System; Technology; Test Result; Testing; Time; Training; Universities; Viral; Virus; amplification detection; base; condyloma; cost; cross reactivity; design; digital; follow-up; improved; innovation; instrumentation; malignant mouth neoplasm; malignant oropharynx neoplasm; mortality; nucleic acid detection; operation; oral infection; particle; pathogen; point of care; prevent; prototype; public health relevance; research study; screening; transcriptome sequencing; viral DNA; viral detection; virus related cancer; waiver

 DESCRIPTION (provided by applicant): The human Papilloma Virus (HPV) causes a wide variety of diseases in humans including squamous papilloma, focal epithelial hyperplasia, verruca vulgaris and condyloma acuminatum. In addition to benign diseases, HPV infection is implicated as an etiologic agent in malignancies including cervical and anogenital cancer. HPV-16 has been identified as the most common HPV genotype associated with oropharyngeal carcinoma. Morbidity / mortality rates associated with these diseases can be substantial, particularly when diagnosis is delayed. According to recent estimates, 7% of the US population is infected with oral HPV and 1% with HPV-16. Annually, about 8,400 people in the USA are diagnosed with cancers of the oropharynx that may be caused by HPV. It is projected that the number of HPV-related oropharyngeal cancers will increase significantly in the future. Currently, HPV detection is carried out in centralized laboratories. The availability of a chair-side molecula test will allow dentists to detect HPV 16 and use the test results to guide patient management. Early detection of HPV-related cancers will reduce morbidity, mortality, and cost. The dentist office is a critical point of intervention for screens for HPV and other infectious agents in the oal cavity. The long-term goal of this project is a multiplex screening platform for HPV and other viral, bacterial and fungal pathogens that go undiagnosed until they have progressed to an advanced stage and are increasingly harmful to health and more difficult to treat. The isothermal amplification chemistry under development is versatile and tests for several pathogens detectable in the oral cavity are under development. Providing tests that can be performed at point of care in the dentist office by a hygienist with no training in diagnostics are part of a company-wide strategy to enter the molecular diagnostics market by supplying the first true point of care molecular diagnostic devices. The first of Lucigen's POC is due to enter clinical trials early 2015. CLIA-waiver will require a level of design well beyond the typical diagnostic device to allow simplicity for use without extensive training or additional equipment for sample preparation. No such CLIA- waived, point of care molecular devices are currently available for any disease or sample type, making this proposal highly innovative. Alternative POC tests are not sensitive or specific enough for reliable diagnosis. Available molecular diagnostics require expensive, complex instrumentation, extensive training for operation and interpretation, and separate sample processing. Lucigen will collaborate with University of Pennsylvania (Penn) to develop an inexpensive, automated, POC device for molecular detection of HPV 16 in saliva. Lucigen will develop the isothermal DNA amplification mixes suitable for use with the Penn-designed multifunctional, isothermal enzymatic amplification reactor for nucleic acid detection. Phase I will focus on assay and prototype (breadboard) development and will provide a proof of concept of the diagnostic device.

 描述（由申请方提供）：人乳头瘤病毒（HPV）可引起多种人类疾病，包括鳞状乳头瘤、局灶性上皮增生、寻常疣和尖锐湿疣。除良性疾病外，HPV感染也是包括宫颈癌和肛门生殖器癌在内的恶性肿瘤的病原体。HPV-16已被确定为与口咽癌相关的最常见的HPV基因型。与这些疾病相关的发病率/死亡率可能很高，特别是在诊断延误时。根据最近的估计，7%的美国人口感染口腔HPV，1%感染HPV-16。每年，美国约有8，400人被诊断患有可能由HPV引起的口咽癌。据预测，HPV相关口咽癌的数量将在未来显着增加。目前，HPV检测在集中实验室进行。椅旁分子检测的可用性将允许牙医检测HPV 16，并使用检测结果来指导患者管理。HPV相关癌症的早期检测将降低发病率，死亡率和成本。 牙科诊所是筛查HPV和其他感染性病原体的关键干预点。该项目的长期目标是为HPV和其他病毒、细菌和真菌病原体建立一个多重筛查平台，这些病原体在发展到晚期之前无法诊断，对健康的危害越来越大，也越来越难以治疗。正在开发的等温扩增化学技术是通用的，对口腔中可检测到的几种病原体的检测也在开发中。通过提供第一个真正的护理点分子诊断设备，提供可以由没有接受过诊断培训的牙医在牙科诊所的护理点进行的测试，是公司进入分子诊断市场的战略的一部分。Lucigen的第一个POC将于2015年初进入临床试验。CLIA豁免将要求设计水平远远超过典型的诊断设备，以允许简单的使用，而无需大量的培训或额外的样品制备设备。目前没有此类CLIA豁免的即时护理分子装置可用于任何疾病或样品类型，使得该提议具有高度创新性。替代POC测试不够敏感或特异性，无法进行可靠的诊断。可用的分子诊断需要昂贵、复杂的仪器、操作和解释的广泛培训以及单独的样品处理。 Lucigen将与宾夕法尼亚大学（Penn）合作开发一种廉价的自动化POC设备，用于唾液中HPV 16的分子检测。Lucigen将开发适合与Penn-designed多功能等温酶扩增反应器一起使用的等温DNA扩增混合物，用于核酸检测。第一阶段将侧重于检测和原型（试验板）开发，并将提供诊断设备的概念验证。