RAPID ELECTROCHEMICAL BIOSENSOR FOR POINT-OF-CARE DIAGNOSIS OF JOINT INFECTION

用于关节感染护理点诊断的快速电化学生物传感器

• 批准号: 10570823
• 负责人: Andrew Neil Fleischman
• 金额: $ 47.08万
• 依托单位: CLEU DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570823
• 关键词: Accident and Emergency department; Altitude; Android; Ascorbic Acid; Bacterial Infections; Benchmarking; Biological Assay; Biosensor; Blood; Cells; Chemicals; Chemistry; Clinical; Clinical Research; Color; Complication; Consensus; Cytolysis; Dedications; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Dryness; Dyes; Electrodes; Electromagnetics; Engineering; Erythema; Evaluation; Failure; Genus Mycobacterium; Goals; Hemoglobin; Hip Joint; Hospitalization; Humidity; Implant; Incidence; Incubated; Infection; Infectious Agent; Injections; International; Joints; Knee joint; Laboratories; Life; Liquid substance; Measurement; Mechanics; Meta-Analysis; Modification; Molds; Morbidity - disease rate; Multi-site clinical study; Multicenter Studies; Nature; Neutrophil Infiltration; Noise; Operative Surgical Procedures; Orthopedics; Outcome; Pain; Patients; Peptide Hydrolases; Performance; Periprosthetic joint infection; Persistent pain; Phase; Physicians; Predictive Value; Process; Production; Provider; Reaction; Reagent; Replacement Arthroplasty; Reporting; Reproducibility; Safety; Sampling; Signal Transduction; Site; Specific qualifier value; Specimen; Stress Tests; Surface; Suspensions; Swelling; Synovial Fluid; System; Temperature; Testing; Translating; Urinalysis; Validation; accurate diagnosis; antimicrobial; cost; design; diagnostic accuracy; diagnostic assay; diagnostic platform; diagnostic technologies; diagnostic tool; diagnostic value; esterase; graphical user interface; handheld equipment; high risk; improved; infection management; innovation; joint infection; leukocyte esterase; manufacture; manufacturing process; meetings; mobile application; mortality; operation; overtreatment; pathogen; point of care; point-of-care diagnosis; point-of-care diagnostics; printed circuit board; prototype; research clinical testing; safety testing; sensor; stability testing; standard of care

Periprosthetic joint infection (PJI) is a devastating complication following total joint replacement (TJR) often with major long-term consequences and morbidity. As many as 100,000 orthopedic infections are diagnosed each year in the US, a number that is expected to rise exponentially. However, the scope of the problem is much larger. Persistent pain is reported in up to 80% of patients after joint surgery, and all painful orthopedic implants require a complete evaluation to rule out the possibility of PJI. Concern for infection is also the single most common reason for patients to present to the emergency department after TJR. Unfortunately, making the diagnosis of infection remains a major challenge, especially since outward clinical signs, such as erythema and swelling, are not specific to PJI. Immediate and accurate diagnoses that also avoid unnecessary overtreatment are critical for favorable outcomes, especially given that PJI management often requires multiple operations and prolonged hospitalization. Nevertheless, underlying infections still commonly go undetected due the nature of existing diagnostics, which are outdated, slow, and imprecise. Problems include the inability to isolate infectious organism(s) in 20-50% of cases (‘culture-negative’), long incubation times required to isolate certain pathogens, and the relatively high incidence of false positives. Alternative diagnostic tools are also limited – either synovial fluid must be transported to a central laboratory for testing or outdated point-of-care (POC) diagnostic technology must still be employed that yields less accurate, binary results (‘infected’ or not). So how should physicians make timely and accurate diagnoses? Our team was the first to discover the diagnostic value of synovial fluid leukocyte esterase (LE), an antimicrobial protease released by activated neutrophils recruited to sites of bacterial infection. Since that discovery, the original LE ‘dipstick’ test (Roche Chemstrip®) has been used by physician to aid in PJI diagnosis with a high diagnostic accuracy of about 89% and a negative predictive value as high as 97%. Nevertheless, the test in its original form designed for urinalysis is impractical for widespread use in orthopedics. The ‘dipstick’ is a dry chemical reagent pad, in which a surface reagent reacts with esterase in the sample to produce a purple dye. The result is read by a clinician based on the degree of color change on the test pad. Unfortunately, lack of objectivity severely limits its clinical reliability. Joint fluid samples must also be centrifuged in an attempt to remove blood and debris that can distort results. Our breakthrough LE test is a POC diagnostic assay that provides a rapid quantitative LE measurement with just a tiny droplet of synovial fluid. Results are immediately available to providers via a mobile app in just 2 minutes to drive clinical decisions. In Phase I, we overcame significant challenges and delivered a highly stable production-ready prototype without signal drift or matrix interference, and designed a low-cost analyzer. Our Phase II goals are to prepare for scale manufacturing of production LE sensors and analyzers, perform master validation to establish product claims for FDA clearance, and conduct a multi-center study to determine real-world diagnostic accuracy of the device in the field.

人假体关节感染（PJI）是一项毁灭性的汇编，经常与 长期的固定性和病态性多达100,000个骨科感染 在美国，这是一个期望的人，这个问题的范围很大。 在手术后，持续的疼痛较大。 需要完全评估PJI的可能性。 不幸的是，患者将患者出现给急诊室 感染的诊断仍然是一个重大挑战，尤其是临床的临床体征，例如红斑和 肿胀不是PJI的特异性。 对于有利的结果至关重要，尤其是考虑到需要多个操作和 但是，长期的Hosspitation。 现有的诊断，过时，缓慢且不精确。 20-50％的Casses（“培养阴性”）中有生物体，隔离某些病原体需要的较长孵化时间， 假阳性的相对高发病率也有限 流体必须运送到中央实验室进行测试或过时的护理（POC）诊断技术 仍然必须使用Thaeld的二进制结果（是否为“感染”）。 及时，准确的诊断？ 酯酶（LE），被激活的嗜中性粒细胞释放的抗菌原质，这些嗜中性粒细胞招募到了bactorial感染部位。 自从发现以来，原始的Le'Dipstick'测试（RocheChemstrip®）已被Sician使用来帮助PJI 高诊断值高达97％的诊断。 然而，对于尿液分析而形成的原始测试对于广泛的骨科使用是不切实际的。 “量强壮”是干燥的化学补品垫 产生紫色的染料。 不幸的是，缺乏客观性严重性限制是临床可靠性。 为了消除血液并扭曲结果。 仅使用一小滴滑液提供了快速定量测量的测定 立即通过移动应用程序在短短2分钟内就可以在第一阶段进行临床决策。 克服了重大挑战，并提供了高度稳定的生产准备原型，而没有信号漂移或 矩阵干扰，并设计了我们的II阶段目标。 生产LE传感器和分析仪，对FDA清除的建立产品索赔进行主验证， 并进行多中心研究，以确定该设备在现场的现实诊断准确性。