An antibiogram-based CentriCapillary system for neonatal sepsis PID and AST

基于抗菌谱的 CentriCapillary 系统，用于治疗新生儿败血症 PID 和 AST

基本信息

批准号：
9170096
负责人：
Vincent Jen-Jr Gau
金额：
$ 74.77万
依托单位：
GENEFLUIDICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9170096
关键词：
Address Adult Adverse event Agreement Algorithms Antibiotics Antimicrobial susceptibility Bacteremia Bacteria Bacterial Infections Beds Biosensor Birth Blood Blood Cells Blood Volume Blood specimen Blood-Borne Pathogens CDC7 gene Centers for Disease Control and Prevention (U.S.)Centrifugation Characteristics Clinical Clinical Microbiology Clinical Sensitivity Cytolysis Development Devices Diagnostic Diagnostic tests Emerging Communicable Diseases Feasibility Studies Goals Guidelines Health Hospitals Hour Hybrids Infant Infection Libraries Marketing Medical Microfluidics Minimum Inhibitory Concentration measurement Molecular Molecular Analysis Neonatal Neonatal Intensive Care Units Phase Premature Infant Procedures Publishing Recovery Regulation Research Risk Sampling Sepsis Small Business Innovation Research Grant Specificity System Systems Development Technology Testing Ultracentrifugation United States Urinary tract infection Urine Validation Whole Blood base blind design evidence base innovation neonatal sepsis neonate novel pathogen phase 2 study premature product development prototype screening validation studies

项目摘要

DESCRIPTION (provided by applicant): The key objective of this proposed product development effort is to optimize the treatment of infections and reduce adverse events associated with inappropriate antibiotic use according to each NICU's locally established antibiogram with a fully automated, evidence-based rapid PID/AST system. The ultimate goal of the proposed neonatal sepsis CentriCapillary system after successful completion of this SBIR fast track is to initially address analysis needs in NICU settings then in the entire blood culture market (currently estimated to total more than $3 billion in the United States alone). Neonates are not small adults. It is not practical to design a diagnostics system using 10 mL blood culture bottles for adults and only load 1 mL of blood sample for neonates. Undoubtedly, there is a risk of missing the target pathogen for extremely low-level bacteremia (e.g., below 1 CFU/mL) using small blood sample volume, but it is not practical or even possible to obtain more than 1 mL of blood routinely from neonates in the NICU for PID and AST lab tests. Currently, there is no commercial system or product development effort from major diagnostics companies to address neonatal sepsis screening specifically using smaller blood volume. We developed, demonstrated and published an innovative molecular-based genotypic-phenotypic-hybrid approach for multiplexed bacterial PID and AST profiling with 100% clinical sensitivity, 96% clinical specificity, 98% minimum inhibitory concentration (MIC) and 97% categorical agreement in our most recent ongoing clinical feasibility study on 73 raw clinical urine samples. In this fas track SBIR project, we will leverage our expertise in microfluidics, electrochemical biosensors, and clinical microbiology to develop an integrated CentriCapillary system. While our molecular analysis technology has been validated with multidrugresistant pathogens (MDR) that cause UTI, which is the most common bacterial infection, it is anticipated that the incorporation of the lysis-centrifugation and dynamic hybridization will have applicability for rapid neonatal sepsis PID/AST and other emerging infectious diseases. PHASE I STUDY (YEAR 1) Specific Aim 1: Transition the current PID/AST platform technology from urinary tract infection (UTI) to neonatal sepsis- Hypothesis: Lysis centrifugation can address the change of matrix effect from raw urine to whole blood samples and the issue of low abundant pathogen for neonatal sepsis by using a CentriCapillary cartridge for blood- pelleting assisted rapid blood culture on various low blood volumes from neonates (10 μL - 2 mL). Specific Aim 2: Demonstrate the feasibility of the electrochemical-based molecular analysis CentriCapillary cartridge - Hypothesis: Microfluidic cartridge-based blood pelleting can capture and recover all common pathogens on the YNHH NICU's antibiogram for rapid neonatal sepsis PID and AST. PHASE II STUDY (YEARS 2 AND 3). Specific Aim 3: Develop a dual-mode electrochemical-based dynamic hybridization analysis algorithm to expand the PID/AST panel - Hypothesis: Dynamic hybridization analysis can be utilized to expand the species-specific identification of common and emerging pathogens for neonatal sepsis. Specific Aim 4: Prototype, validate and manufacture the CentriCapillary cartridge (COGS<$15) and system (COGS<$25k) - Hypothesis: Ultracentrifugation (up to 50,000 g, gravitational force) can be incorporated into a multiplexed fluidic cartridge for a fully automated neonatal sepsis PID/AST from whole blood samples in 6 hours. Specific Aim 5: Clinically validate the rapid neonatal PID/AST CentriCapillary system according to CLSI guidelines - Hypothesis: Blood samples spiked with ATCC strain bacteria used in the analytical validation studies represent critical matrix characteristics of fresh whole blood samples from neonates The development and validation of neonatal sepsis will adhere to the ISO 13485 standards, FDA/CDC/CLSI guidelines on AST and federal regulation 21 CFR 866.1645. The ultimate goal of this study is to reduce adverse events associated with inappropriate antibiotic use in the NICU settings.

描述（由适用提供）：根据每个NICU的本地建立的抗生素抗生素图，并使用具有完全自动化的基于证据的快速PID/AST系统的每个NICU，根据每个NICU的本地建立的抗体图来优化感染治疗并减少与不适当使用抗生素相关的不良事件的关键目标。成功完成此SBIR快速轨道后，提议的新生儿败血症中心乳头系统的最终目标是最初解决NICU环境中的分析需求，然后在整个血液培养中市场（目前估计仅在美国，总计超过30亿美元）。新生儿不是小成年人。使用10毫升血液培养瓶为成人设计诊断系统并不实用，而新生儿的血液样本仅为1 ml血液样本。毫无疑问，使用小血液样本体积缺少极低水平细菌（例如，低于1 CFU/mL）的靶病原体的风险，但是从NICU中的NICU中的NICU和AST Lab Lab测试从NICU和AST实验室测试中通常获得超过1 ml的血液是不切实际的，甚至不可能。当前，主要诊断公司尚无商业系统或产品开发工作，可以专门使用较小的血液量来解决新生儿败血症筛查。我们开发，证明和发表了一种创新的基于分子的基因型 - 型 - 杂交方法，用于多重细菌PID和具有100％临床敏感性的AST分析，96％临床特异性，98％的最小抑制浓度（MIC）（MIC）和97％的临床临床临床性研究中的最低抑制性浓度（MIC）和97％的分类性一致性。在这个FAS Track SBIR项目中，我们将利用微流体，电化学生物传感器和临床微生物学方面的专业知识来开发综合的中心乳头系统。虽然我们的分子分析技术已经用导致UTI（最常见的细菌感染的UTI）进行了多瑞抗耐药病原体（MDR）验证，但预计将裂解中心置换和动态杂交纳入将具有快速的新生儿脓毒症PID/AST/AST/AST和其他出现的感染。第一阶段研究（第1年）具体目的1：过渡当前的PID/AST平台技术从尿路感染（UTI）到新生儿脓毒症 - 假设：裂解离心可以解决基质效应的变化，从原始尿液到全血样品的变化从原始尿液变为全血样品，以及通过使用较低的流血的流血来探讨低丰富的病原体的问题新生儿（10μL -2 mL）。具体目的2：证明基于电化学的分子分析的可行性中心毛囊 - 假设：基于微流体的基于基于YNHH NICU的NICU抗体图上快速新生儿Sepsis PID和AST上的基于微流体墨盒的血液沉淀。第二阶段研究（第2和3年）。具体目的3：开发基于双模式的基于双模式的动态杂交分析算法以扩展PID/AST面板 - 假设：可以利用动态杂交分析来扩展新生儿败血症的常见和新兴病原体的特定规格鉴定。特定目标4：原型，验证和制造中心毛囊（COGS <$ 15）和系统（COGS <$ 25K） - 假设：超速离心（高达50,000 g，重力，引力力）可以掺入全部多路复用盒中在6小时内从全血样品中自动化的新生儿败血症/AST。具体目的5：根据CLSI指南，在临床上验证了新生儿PID/AST中心乳头系统的快速验证 - 假设：分析验证研究中使用的ATCC菌株细菌尖叫的血液样本代表了来自新鲜全血样品的关键基质特征，来自新鲜全血样品的新生儿的开发和验证是Neonatal SEPIS的开发和验证的NEONATAL SEPIS/CLS/CLS CLSI clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi clsi cldi inso inso 1348 Onerail f. AST和联邦法规21 CFR 866.1645。这项研究的最终目的是减少与NICU环境中不适当使用抗生素相关的不良事件。