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

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，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，是所有年龄组患者发病率和医疗保健支出的主要原因。据估计，每年有700多万门诊就诊和100多万住院与尿路感染有关。高达10%的尿路感染导致严重的并发症，如革兰氏阴性脓毒症或慢性肾盂肾炎伴肾功能丧失。根据国家肾脏和泌尿系统疾病信息中心（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患者（141万名男性；686万名女性）的主要诊断。2000年，美国卫生保健系统每年用于UTI（评估和治疗）的总费用为35亿美元（男性10亿美元，女性25亿美元）。由于尿路感染非常普遍，大多数临床微生物实验室每天都要处理大量尿液标本，这占尿路感染相关医疗费用的很大一部分。虽然经验性和快速尿路感染筛查试验（例如，尿液显微镜和基于化学的试纸分析）非常快，但它们不是非常敏感或无法识别引起尿路感染的病原体。另一方面，基于培养的方法是准确和可靠的，并且允许细菌鉴定，但在获得结果之前至少需要培养过夜。因此，在标本收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建议通过改进侧流分析的设计和尿液样本所需的前期样品制备步骤，开发一种经济实惠且易于获得的尿路感染诊断POC分子检测方法。侧流试纸将被设计为针对主要uti相关病原体群的细菌16S rRNA，并通过在试纸上放置排列的核酸捕获线来进行细菌的种类鉴定。快速识别阴性样品的能力将消除培养收集的所有样品的需要。尿路病原体的阳性结果将为医生提供更多的信息，以避免假定的治疗，并为患者开出有效的药物以获得更好的结果。

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.