Arrayed Lateral Flow Biosensor for Rapid Molecular Identification of UTI-Related

用于尿路感染相关快速分子鉴定的阵列侧流生物传感器

• 批准号: 8393124
• 负责人: ANJAL C SHARMA
• 金额: $ 19.51万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-02 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8393124
• 关键词: Academic Medical Centers; Admission activity; Advanced Development; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Bacteria; Bacterial Infections; Biological Assay; Biosensor; Bladder; Buffers; Caring; Cells; Chemicals; Chronic; Ciprofloxacin; Cities; Clinical; Clinical Microbiology; Collection; Cytolysis; DNA; Detection; Development; Devices; Diagnosis; Diagnostic; Enterococcus; Enzymes; Escherichia coli; Evaluation; Expenditure; Gold; Group Identifications; Health Care Costs; Health Expenditures; Healthcare; Healthcare Systems; Hospitals; Image; Infection; Investigation; Kidney; Kidney Diseases; Klebsiella pneumonia bacterium; Label; Laboratories; Lateral; Lead; Leukocytes; Levaquin; Membrane; Methods; Microscopy; Molecular; Morbidity - disease rate; Nitrites; Nitrofurantoin; Nucleic Acids; Nurses; Office Visits; Organ; Outcome; Outpatients; Patients; Pharmaceutical Preparations; Phase; Physicians; Physicians' Offices; Predisposition; Preparation; Proteus mirabilis; Pseudomonas aeruginosa; Pyelonephritis; Quick Test for Liver Function; Renal function; Reporting; Ribosomal RNA; Sampling; Scheme; Screening procedure; Sepsis; Signal Transduction; Specimen Handling; Staining method; Stains; Symptoms; System; Systems Analysis; Technology; Telephone; Testing; Time; United States; Ureter; Urethra; Urinary tract; Urinary tract infection; Urine; Urologic Diseases; Uropathogen; Visit; Woman; age group; base; cost; culture plates; design; human disease; improved; innovation; men; nucleic acid detection; pathogen; response; sample collection; wasting

DESCRIPTION (provided by applicant): The aim of this application is to develop a rapid, easy-to-use, and inexpensive test for urinary tract infection diagnosis using an ultrasensitive arrayed lateral flow nucleic acid biosensor (LFNAB) to identify uropathogens. UTI is the most common urological disease in the United States and is a major cause of patient morbidity and health care expenditure for all age groups. It was estimated that over 7 million office visits and more than 1 million hospital admissions per year are UTI related. Up to 10% of UTIs result in serious complications such as gram-negative sepsis or chronic pyelonephritis with loss of renal function. According to information provided by the National Kidney & Urologic Diseases Information Clearinghouse (NKUDIC), UTI was listed as the primary diagnosis for 8.27 million physician office and hospital outpatient visits (1.41 million men; 6.86 million women) in year 2000. The annual total cost of UTI (evaluation and treatment) to the United States health care system was 3.5 billion ($1 billion for men; $2.5 billion for women) in year 2000. Because UTI is so common, large numbers of urine specimens are processed daily in most clinical microbiology laboratories and this comprises a significant component of these health care costs involve UTI. While empirical and rapid UTI screening tests (e.g., urine microscopy and chemical-based dipsticks analysis) are very fast, they are not very sensitive or do not have the ability to identiy the UTI causing pathogens. On the other hand, the culture-based method is accurate and reliable and allows bacterial identification but requires at least an overnight incubation of cultures before results are available. Thus it is very common to have a time lag of approximately 2 days between specimen collection and pathogen identification. To this end, Lynntech proposes to develop an affordable and accessible POC molecular assay for UTI diagnosis by improving the design of the lateral flow assay and the upfront sample preparation step needed for urine samples. The lateral flow strip will be designed to target bacterial 16S rRNA of major UTI-related pathogen groups and to allow species identification of bacteria by putting arrayed nucleic acid capturing lines on the strip. The ability to quickly identify negative samples will eliminate the need to culture all the samples collected. A positive result with uropathogens identified will give physicians more information to avoid presumptive treatments and prescribe effective medication to patients for better outcomes. PUBLIC HEALTH RELEVANCE: A urinary tract infection (UTI) is an infection that can happen anywhere along the urinary tract (urethra, bladder, kidneys, and ureters). UTI is among the most common diseases of humans and is the most common urological disease in the United States and is a major cause of patient morbidity and health care expenditure for all age groups. This project will advance the development of a molecular diagnostic device for the rapid and inexpensive detection of uropathogens. We expect our technology will lead to an assay that will allow clinicians to provide more than empirical UTI treatments initially. A rapid report of a negative result will eliminate the need for UTI-based treatment/therapy and the physicians can focus on the investigation of other possible reasons for the illness. Secondly, a positive result with uropathogens identified will give physicians more information to avoid presumptive treatments and prescribe effective medication to patients. Having the information on the identity of the pathogen(s) involved also allows physicians to better prescribe antibiotics without contributing to growing antimicrobial resistance.

描述（由申请人提供）：本申请的目的是开发一种快速、易于使用且廉价的尿路感染诊断测试，使用超灵敏阵列侧流核酸生物传感器（LFNAB）来识别尿路病原体。尿路感染是美国最常见的泌尿系统疾病，是所有年龄段患者发病和医疗保健支出的主要原因。据估计，每年有超过 700 万人次就诊和超过 100 万人次住院与尿路感染有关。高达 10% 的尿路感染会导致严重并发症，例如革兰氏阴性败血症或伴有肾功能丧失的慢性肾盂肾炎。根据国家肾脏和泌尿系统疾病信息交换所 (NKUDIC) 提供的信息，2000 年，尿路感染被列为 827 万名医生办公室和医院门诊就诊的主要诊断（141 万名男性；686 万名女性）。当年美国医疗保健系统的 UTI（评估和治疗）费用为 35 亿美元（男性 10 亿美元；女性 25 亿美元） 2000. 由于尿路感染如此常见，大多数临床微生物学实验室每天都会处理大量尿液样本，这构成了涉及尿路感染的医疗保健成本的重要组成部分。虽然经验和快速尿路感染筛查测试（例如尿液显微镜检查和基于化学的试纸分析）非常快，但它们不是很敏感或没有能力识别引起尿路感染的病原体。另一方面，基于培养的方法准确可靠，可以进行细菌鉴定，但在获得结果之前至少需要培养过夜。因此，标本采集和病原体鉴定之间有大约 2 天的时间滞后是很常见的。为此，Lynntech 建议通过改进侧流检测的设计和尿液样本所需的前期样本制备步骤，开发一种负担得起且易于使用的 POC 分子检测，用于 UTI 诊断。侧流试纸条将设计用于靶向主要 UTI 相关病原体群的细菌 16S rRNA，并通过在试纸条上放置排列好的核酸捕获线来实现细菌的物种鉴定。快速识别阴性样本的能力将消除对收集的所有样本进行培养的需要。确定尿路病原体的阳性结果将为医生提供更多信息，以避免推定治疗，并为患者开出有效的药物以获得更好的结果。 公共卫生相关性：尿路感染 (UTI) 是一种可能发生在尿路任何部位（尿道、膀胱、肾脏和输尿管）的感染。尿路感染是人类最常见的疾病之一，也是美国最常见的泌尿系统疾病，是所有年龄段患者发病和医疗保健支出的主要原因。该项目将推动分子诊断设备的开发，以快速且廉价地检测尿路病原体。我们预计我们的技术将带来一种检测方法，使临床医生最初能够提供的不仅仅是经验性尿路感染治疗。快速报告阴性结果将消除基于尿路感染的治疗/治疗的需要，医生可以专注于调查其他可能的疾病原因。其次，确定尿路病原体的阳性结果将为医生提供更多信息，以避免推定治疗并为患者开出有效的药物。掌握有关病原体身份的信息还可以让医生更好地开抗生素处方，而不会增加抗菌素耐药性。