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、易于使用且廉价的用于尿路感染诊断的测试，其使用超灵敏的阵列侧向流核酸生物传感器（LFNAB）来识别尿路病原体。UTI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，每年有超过700万的办公室访问和超过100万的医院入院与UTI有关。高达10%的尿路感染会导致严重并发症，例如革兰氏阴性脓毒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，UTI被列为2000年827万医生办公室和医院门诊就诊的主要诊断（141万男性; 686万女性）。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UTI是如此常见，在大多数临床微生物实验室每天处理大量的尿液标本，这构成了涉及UTI的这些医疗保健成本的重要组成部分。虽然经验和快速UTI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，但它们不是非常敏感或不具有鉴定引起UTI的病原体的能力。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，在标本采集和病原体鉴定之间存在约2天的时间差是非常常见的。为此，Lynntech提出通过改进侧流检测的设计和尿样所需的前期样品制备步骤，开发一种负担得起且易于获得的用于UTI诊断的POC分子检测。侧向流条将被设计为靶向主要UTI相关病原体组的细菌16 S rRNA，并允许通过在条上放置阵列核酸捕获线来鉴定细菌的种属。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。确定的尿路病原体的阳性结果将为医生提供更多信息，以避免假定治疗，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：泌尿道感染（UTI）是一种可发生在泌尿道（尿道、膀胱、肾脏和输尿管）沿着任何地方的感染。UTI是人类最常见的疾病之一，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。该项目将推进分子诊断设备的开发，用于快速和廉价的尿路病原体检测。我们希望我们的技术将导致一种检测方法，使临床医生能够提供更多的经验性UTI治疗。阴性结果的快速报告将消除对基于UTI的治疗/疗法的需要，并且医生可以专注于疾病的其他可能原因的调查。其次，阳性结果与尿路病原体确定将给医生更多的信息，以避免推定的治疗和处方有效的药物给病人。掌握相关病原体的身份信息也可以让医生更好地开抗生素处方，而不会导致抗生素耐药性的增加。

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.