DNA Analysis in Multi-Phase Microfabricated Devices

描述（由申请人提供）：传染病是一个重大的医疗费用负担。对于细菌感染，特别是慢性感染，选择抗生素进行治疗，而不知道所选药物是否适合感染病原体。虽然病毒感染几乎没有有效的治疗方法，但患者在离开初级保健医生办公室之前希望药物治疗。抗生素通常用于治疗病毒感染，因为患者需要它们而没有意识到它们是无效的，或者医生提供它们作为预防措施。显然，快速准确地识别传染性病原体将减少不必要的处方、减少住院时间并减少抗生素耐药微生物的传播。我们建议开发一个遗传分析微流控系统，使用一个单一的气动输入流体控制，和一个多路复用的反应系统的物种识别。该设备将使用一系列反应室，然后是一个分离通道，以确定感染因子的类别及其对抗生素的特异性抗性。我们将针对与急性（普通感冒）和慢性（多种细菌）呼吸道感染相关的病原体进行主要应用。我们选择这些目标领域有几个原因。首先，对于我们的小设备尺寸策略，我们需要具有足够病原体负载的样本来完成对拭子、痰或鼻洗液中的患者材料的分析，因为这些疾病通常具有较高的病原体数量。其次，了解不同的病原体物种和菌株及其感染时间过程可以导致更好的治疗和减少抗生素的使用。最后，该设备可以很容易地扩展到其他病毒，细菌因子或基因组分析，只需改变试剂。

DESCRIPTION (provided by applicant): Infectious diseases represent a significant healthcare cost burden. For bacterial infections, especially chronic ones, antibiotics are selected for treatment not knowing whether the drugs selected are appropriate for the infecting pathogen. Although viral infections have few effective treatments, patients desire medication before they leave their primary care physician's office. Antibiotics are often prescribed for viral infections because the patient demands them not realizing they are ineffective, or the physician provides them as a precautionary measure. Clearly, rapidly and accurately identifying infectious pathogens will lead to fewer unnecessary prescriptions, reduced hospitalization time, and a reduction in the spread of antibiotic resistant microbes. We propose to develop a genetic analysis microfluidic system that uses a single pneumatic input for fluidic control, and a multiplexed reaction system for species identification. The device will use a series of reaction chambers followed by a separation channel to determine the class of infecting agents and their specific resistance to antibiotics. We will target pathogens associated with acute (the common cold) and chronic (multiple-species bacterial) respiratory infections for our main applications. We choose these target areas for several reasons. First, for our strategy of small device size, we need a sample with sufficient pathogenic load to complete an analysis patient material from a swab, sputum, or nasal wash for these diseases typically has high pathogen numbers. Second, understanding the different pathogen species and strains and their infection time course could lead to better treatment and lower the use of antibiotics. Finally, the device can easily be extended to other viruses, bacterial agents, or genomic analysis with merely a change in the reagents.