Rapid, low cost, point-of-care diagnostic device for Group B streptococcus

描述（由申请人提供）：快速识别围产期潜在感染的能力需要高度敏感，特异性，廉价，易于使用的诊断工具，并且位于初级保健机构。B群链球菌（GBS）是新生儿早发性败血症和肺炎的主要原因。早发性疾病的主要危险因素是分娩时的母体定植。据计算，基于筛查的策略可以减少早发新生儿GBS疾病高达78%。如果在分娩前5周内收集培养物，并且同时检查阴道和直肠样本，则预测分娩时GBS携带的筛查准确性更高。微生物培养方法包括在固体培养基上直接电镀和使用选择性肉汤培养基。已经开发了新的技术来提高灵敏度或减少GBS检测的时间。然而，这种技术通常成本较高，并且需要常规测试无法普遍获得的技能和技术。拟议项目的重点是开发一种快速、易于使用、高度敏感和特异性高、同时具有成本效益的GBS即时诊断方法。该传感器由密歇根州立大学（Michigan State University）发明，使用电导检测技术，并已在实验室中得到验证，可在6至10分钟内产生定性结果，对大肠杆菌的检测限较低，为79个细胞/ml。I期项目的总体目标是证明生物传感器技术作为一种单一病原体检测方法在接种阴道拭子样本中检测GBS的可行性。具体地说，利用初步研究的方法，将制造单目标生物传感器，用于检测肉汤（纯）培养中的无乳链球菌。然后，将与密歇根大学合作制定方案，在使用生物传感器进行测试之前处理和准备阴道拭子样本。因此，将证明生物传感器用于阴道拭子样品的可行性。样品制备和测试的综合时间目标在30分钟以内。二期研究将重点关注传感器设计修改，以提高生物传感器的灵敏度，优化生物传感器的动态检测范围，以快速诊断阴道和直肠拭子中的GBS，实现传感器条的批量生产，并开发样品处理和处理模块，以减少人工需求，促进护理点使用。第二阶段的工业伙伴关系已经到位。在第二阶段之后，将进行临床试验，然后寻求FDA对诊断设备的批准。公共卫生相关性：所提出的生物传感器价格低廉，非常适合于快速检测拭子样本中的GBS。这将有助于医疗保健提供者在新生儿分娩前和分娩期间迅速识别围产期感染的可能性，并有助于适当的靶向抗生素治疗。这还将防止因滥用抗生素而导致GBS对抗生素的耐药性增加，并减少与误诊疾病和不必要住院有关的卫生费用和工时损失。电导传感器技术的商业化将使全世界人类生活的整体质量得到改善。

DESCRIPTION (provided by applicant): The ability to rapidly identify the potential for perinatal infections requires diagnostic tools that are highly sensitive, specific, inexpensive, easy to use, and located in primary care settings. Group B streptococcus (GBS) is a leading cause of early-onset sepsis and pneumonia in newborn babies. The major risk factor for early-onset disease is maternal colonization at time of delivery. It has been calculated that the screening-based strategy can reduce early-onset neonatal GBS disease by as much as 78%. Screening accuracy in predicting GBS carriage at delivery is higher if the cultures are collected within 5 weeks before delivery, and when both vaginal and rectal samples are examined. Microbiological culture methods include direct plating on solid media and the use of selective broth media. New techniques have been developed to increase sensitivity or to decrease the time for GBS detection. However, such techniques typically have higher costs and require skills and technologies not universally available for routine testing. The proposed project is focused on developing a point-of-care diagnostic for GBS that is rapid, easy to use, highly sensitive and specific, while being cost-effective. The proposed sensor, invented at Michigan State University, uses a conductimetric detection technique and has been demonstrated in the lab to produce qualitative results in 6 to 10 min with a lower detection limit of 79 cells/ml for E. coli. The overall aim of the Phase I program is to demonstrate the feasibility of the biosensor technology as a single pathogen assay for GBS detection in inoculated vaginal swab samples. Specifically, using methods from preliminary studies, single-target biosensors will be fabricated for detection of S. agalactiae in broth (pure) cultures. Then, protocols will be developed in collaboration with University of Michigan for the processing and preparation of vaginal swab samples prior to testing with the biosensor. Feasibility of the biosensor for use with vaginal swab-based samples will thus be demonstrated. Combined sample preparation and test time is aimed at less than 30 minutes. The Phase II research will focus on the sensor design modifications needed to improve biosensor sensitivity, optimize dynamic detection range of the biosensor for rapid diagnosis of GBS in vaginal as well as rectal swabs, enable mass production of the sensor strips, and develop a sample handling and processing module to facilitate point-of-care use with minimal labor needed. Industrial partnerships are already in place for the Phase II work. Following Phase II, clinical trials will be conducted, and FDA approvals for the diagnostic device will then be sought. PUBLIC HEALTH RELEVANCE: The proposed biosensor is inexpensive and ideally-suited to the task of rapidly detecting GBS in swab samples. This will help healthcare providers quickly identify the potential for perinatal infections just prior and during delivery of new-born infants, and aid appropriate targeted antibiotic treatment. This will also prevent increase in resistance of GBS to antibiotics resulting from indiscriminate use of antibiotics, and reduce health costs and man-hours lost associated with misdiagnosed illnesses and unnecessary hospitalizations. Commercialization of the conductimetric sensor technology will enable improvement in the overall quality of human life all over the world.