Rapid, Point-of-Care Diagnosis of Neonatal Sepsis

新生儿败血症的快速护理点诊断

• 批准号: 8591856
• 负责人: Gregory Sommer
• 金额: $ 14.92万
• 依托单位: SANDSTONE DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591856
• 关键词: Academic Medical Centers; Accounting; Acute; Acute-Phase Proteins; Address; Affect; Algorithms; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Antibodies; Benchmarking; Biological Assay; Biological Markers; Blood; Blood Volume; Blood specimen; C-reactive protein; Cell surface; Cessation of life; Characteristics; Childhood; Classification; Clinical; Clinical Sensitivity; Collection; Computer software; Consumption; Detection; Development; Devices; Diagnosis; Diagnostic; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Feedback; Flow Cytometry; Functional disorder; Funding; Future; Gold; HLA-DR Antigens; Heel; Hematology; Hour; Human Resources; IL8 gene; ITGAM gene; Immunoassay; Immunosuppressive Agents; Infant; Inflammatory Response; Intellectual Property; Interleukin-2; Interleukin-6; Intervention; Investigation; Laboratories; Laboratory Personnel; Lead; Legal patent; Licensing; Ligands; Live Birth; Marketing; Measurement; Measures; Microfluidics; Monitor; Mothers; Neonatal; Neutrophil Activation; Newborn Infant; Nurses; Odds Ratio; Organ; Patients; Pediatric Hospitals; Penetration; Performance; Peripheral; Phase; Physicians; Plasma Proteins; Pregnancy; Preparation; Price; Proteins; Public Health; Reader; Risk; Sampling; Sepsis; Serum amyloid A protein; Small Business Innovation Research Grant; Surface Antigens; System; T-Lymphocyte; TNF gene; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Toxin; Training; Trauma; Tube; United States; United States National Institutes of Health; Up-Regulation; Validation; Whole Blood; Work; antimicrobial; assay development; base; biodefense; chemokine; cost; cytokine; design; experience; follow-up; improved; inflammatory marker; innovation; instrument; interest; meetings; monocyte; mortality; neonatal death; neonatal sepsis; neonate; novel; novel strategies; point of care; point-of-care diagnostics; procalcitonin; product development; public health relevance; rapid diagnosis; screening; tool

DESCRIPTION (provided by applicant): The proposed Phase I SBIR project will support Sandstone Diagnostics, Inc. to demonstrate feasibility of a commercial point-of-care diagnostic system for rapid diagnosis and monitoring of neonatal sepsis using peripheral protein and cellular biomarkers from heel stick blood samples in the NICU. Significance: Neonatal sepsis affects approximately 4 out of every 1000 live births and accounts for nearly half of all neonatal deaths in the United States. Detection of the onset of sepsis and timely intervention with appropriate antimicrobial therapy is critical for survival in neonates. There is an urgent need for improved early diagnostic tools; routine laboratory blood culture (gold standard) suffers from slow analysis time (24 - 48 hours), large sample volume requirement (~1 mL), and high false negative rate. Innovation: Our patent-pending SpinDxTM system uniquely addresses this need by achieving rapid (~15 minute), multiplexed quantitation of protein and cellular biomarkers from small volume (~30 ¿L) whole blood samples. All assays are packaged on one disposable microfluidic disk for fully automated analysis in a portable, battery-powered reader. Approach: We will demonstrate feasibility by: (1) developing assays for a panel of protein and cellular biomarkers shown to be responsive for early detection and monitoring of neonatal sepsis, and (2) packaging and deploying a system to the Stanford Clinical Laboratory for follow-up (Phase II) benchmarking and validation using whole blood samples obtained for routine monitoring in the Lucile Packard Children's Hospital NICU. Target biomarkers include acute phase reactants (CRP, PCT, SAA, LBP), chemokines and cytokines (IL-6, IL-8, TNF¿), hematologic parameters (WBC counts) and cell surface antigens (CD64, CD11b, HLA-DR, CTLA-4). The system is designed for fully automated quantitation of each biomarker from blood samples loaded via pipette or interfaced with heel stick collection tubes commonly used in the NICU. Company: Sandstone Diagnostics, Inc. was founded in April 2012 in Livermore, CA. Company co-founders Schaff and Sommer invented the SpinDxTM technology at Sandia National Laboratories for point-of-care biodefense applications, including NIH U01 funding for an improved toxin diagnostics system. The company has licensed the intellectual property from Sandia for neonatal diagnostic applications. The company's lead advisors have deep executive experience in diagnostic product development, marketing, and FDA clearance. Sandstone is also partnering with Dr. James Faix - a premier thought leader in sepsis diagnostics and management at Stanford University Medical Center. Commercial Market and Customers: The final product will greatly enhance neonatal and pediatric sepsis monitoring capabilities by drastically reducing the time, cost, and sample volume required for testing and diagnosis. The company has received extensive interest and feedback from NICU physicians, nurses, and laboratory personnel who constitute our targeted customer base. The company anticipates penetration into the estimated $1.5 billion global clinical neonatal and pediatric monitoring market within 4 years.

描述（由申请人提供）：拟议的第一阶段SBIR项目将支持Sandstone Diagnostics，Inc.证明商业即时诊断系统的可行性，该系统用于使用来自NICU中足跟采血样本的外周蛋白和细胞生物标志物快速诊断和监测新生儿败血症。重要性：新生儿败血症影响每1000名活产婴儿中的约4名，占美国所有新生儿死亡的近一半。检测败血症的发生并及时进行适当的抗菌治疗对新生儿的生存至关重要。迫切需要 改进早期诊断工具;常规实验室血培养（金标准）具有分析时间慢（24 - 48小时）、需要大的样品体积（~1 mL）和高假阴性率的缺点。创新：我们正在申请专利的SpinDxTM系统通过实现小体积（~30 μ L）全血样本中蛋白质和细胞生物标志物的快速（~15分钟）、多重定量，独特地解决了这一需求。所有检测均包装在一个一次性微流控盘上，以便在便携式电池供电的读取器中进行全自动分析。方法：我们将通过以下方式证明可行性：（1）开发一组蛋白质和细胞生物标志物的检测方法，这些生物标志物对新生儿败血症的早期检测和监测具有响应性，以及（2）将系统包装并部署到斯坦福大学临床实验室，使用Lucile Packard儿童医院NICU常规监测获得的全血样本进行随访（II期）基准和验证。靶生物标志物包括急性期反应物（CRP、PCT、SAA、LBP）、趋化因子和细胞因子（IL-6、IL-8、TNF？）、血液学参数（WBC计数）和细胞表面抗原（CD 64、CD 11b、HLA-DR、CTLA-4）。该系统设计用于通过移液管加载或与NICU中常用的足跟采血管连接的血液样本中的每种生物标志物的全自动定量。公司名称：Sandstone Diagnostics，Inc.成立于2012年4月在利弗莫尔，CA。公司联合创始人Schaff和Sommer在桑迪亚国家实验室发明了SpinDxTM技术，用于即时生物防御应用，包括NIH U 01资助改进的毒素诊断系统。该公司已授权桑迪亚的知识产权用于新生儿诊断应用。该公司的首席顾问在诊断产品开发、营销和FDA批准方面拥有丰富的执行经验。Sandstone还与斯坦福大学医学中心败血症诊断和管理方面的主要思想领袖James Faix博士合作。商业市场和客户：最终产品将大大提高新生儿和儿科败血症监测能力，大大减少测试和诊断所需的时间，成本和样本量。该公司已经收到了来自NICU医生，护士和实验室人员的广泛兴趣和反馈，他们构成了我们的目标客户群。该公司预计将在4年内渗透到估计15亿美元的全球临床新生儿和儿科监测市场。