Electrical System for Rapidly Detecting Viable Bacteria in Blood Culture

用于快速检测血培养中活细菌的电气系统

• 批准号: 8714898
• 负责人: Eugene David Boland
• 金额: $ 96.12万
• 依托单位: TECHSHOT, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714898
• 关键词: Adult; Agitation; Aliquot; Amplifiers; Bacteria; Blood; Blood Volume; Carbon Dioxide; Cataloging; Catalogs; Cell membrane; Cessation of life; Charge; Clinical; Clinical Research; Clinical Trials; Computer software; Culture Media; Custom; Data; Detection; Development; Devices; Electric Capacitance; Electronics; Ensure; Frequencies; Funding; Goals; Gold; Hematocrit procedure; Hospitals; Hour; Infection; Inflammation; Institutional Review Boards; Intensive Care; Investigation; Legal patent; Life; Malignant neoplasm of lung; Manuals; Marketing; Measurement; Measures; Mechanics; Methods; Microbe; Organism; Outcome; Patients; Performance; Phase; Process; Proliferating; Property; Reading; Recording of previous events; Records; Reporting; Research; Sampling; Scanning; Sepsis; Septicemia; Small Business Innovation Research Grant; Steam; Sterility; Suspension substance; Suspensions; System; Technology; Testing; Time; Tissues; arm; base; clinical Diagnosis; clinically relevant; design; electric impedance; electrical measurement; experience; graphical user interface; improved; innovation; instrument; malignant breast neoplasm; meetings; microorganism; mortality; neonate; operation; product development; prototype; public health relevance; research study; response; verification and validation

DESCRIPTION (provided by applicant): Background: Each year in the US, there are over 18 Million Blood Cultures performed to determine the presence/absence of viable microorganisms in the blood of patients suspected of having Blood Steam Infection (BSI or Septicemia). Current technology for Blood Cultures typically takes 1-5 days to provide a result. Our proposed system would enable the user to obtain Blood Culture results in 2-24 hrs. instead which will greatly improve the outcomes for patients with Sepsis. Innovation: At the core of the system lies a patent-pending electrical method, which can detect proliferating microorganisms in suspensions based on charges stored at the intact cell membranes of live microorganisms. This approach was shown (prior to Phase I) to be 4-10X faster than the current methods employed in BACTEC TM (current Gold Std.) However, in order to achieve the desired sensitivity, our method required that aliquots be periodically withdrawn from the broth (blood culture medium + patient blood) into a thin long chamber for an "electrical scan" (impedance measurements are frequencies 1KHz - 100 MHz). The data from this "scan" is then analyzed to calculate the "Bulk Capacitance" (Cb), a parameter that rises with the rise in the number of live microbes. We successfully achieved our Phase I goals by showing that (a) the automated sampling could be repeatedly performed aseptically over 5 days (5x longer than foreseen need); (b) the sophisticated electrical measurements needed could be obtained using a circuit designed and assembled by us; and (c) the threshold concentrations, and hence Times to Detection (TTDs), using our Phase I were much lower than those of BACTEC TM. Approach: In Phase II, we propose to (a) build an 8-unit "research" unit; (b) verify the robustness of our device: its abilit to handle different volumes of blood with different properties such as hematocrit and WBC counts; (c) verify our ability to correctly diagnose clinical samples using the 8-unit system; and (d) design (using "Good Design Principles"& keeping records in a "Device History File") a 64 unit 'market ready' system. By the end of the funded period (3 yrs.), we will be ready to meet with the FDA armed with a Device History File documenting the development of the product (64-unit system) & clinical studies (NB: not clinical trials) showing equivalency to existing devices such as BACTECTM (in terms of being able to correctly identify positives) and also demonstrate improved performance (reduced TTDs) to potential partners and/or investors.

描述（由申请人提供）：背景：每年在美国进行超过1800万次血液培养，以确定疑似血液蒸汽感染（BSI或败血症）患者血液中是否存在活微生物。目前的血液培养技术通常需要1-5天才能提供结果。我们提出的系统将使用户能够在2-24小时内获得血液培养结果。相反，这将大大改善脓毒症患者的预后。创新：该系统的核心是一种正在申请专利的电学方法，该方法可以根据储存在活微生物完整细胞膜上的电荷来检测悬浮液中的增殖微生物。这种方法（在第一阶段之前）比BACTEC TM（当前Gold Std.）中采用的当前方法快4- 10倍。然而，为了达到所需的灵敏度，我们的方法需要定期从肉汤（血液培养基+患者血液）中取出等分试样，放入一个细长的腔室中进行“电扫描”（阻抗测量的频率为1 KHz- 100 MHz）。然后分析来自该“扫描”的数据以计算“体电容”（Cb），这是一个随着活微生物数量的增加而增加的参数。我们成功地实现了第一阶段的目标，证明了：（a）自动采样可以在5天内无菌重复进行（比预期需要长5倍）;（B）可以使用我们设计和组装的电路获得所需的复杂电气测量;（c）阈值浓度，因此检测时间（TTD），使用我们的第一阶段远低于BACTEC TM。方法：在第二阶段，我们建议：（a）建立一个8单元的“研究”单元;（B）验证我们的设备的鲁棒性：它能够处理具有不同性质（如红细胞压积和白细胞计数）的不同体积的血液;（c）验证我们使用8单元系统正确诊断临床样本的能力;及（d）设计（使用“良好设计原则”及在“装置历史档案”中保存记录）64个单位的“市场就绪”系统。到资助期结束时（3年），我们将准备好与FDA会面，并提供设备历史文件，记录产品（64单元系统）的开发和临床研究（NB：非临床试验），显示与现有设备（如BACTECTM）的等效性（在能够正确识别阳性方面），并向潜在合作伙伴和/或投资者展示改进的性能（减少TTD）。