Improved sample preparation has the potential to address a huge unmet need for fast turnaround sepsis tests that enable early administration of appropriate antimicrobial therapy. In recent years, inertial and elasto-inertial microfluidics-based sample preparation has gained substantial interest for bioparticle separation applications. However, for applications in blood stream infections the throughput and bacteria separation efficiency has thus far been limited. In this work, for the first time we report elasto-inertial microfluidics-based bacteria isolation from blood at throughputs and efficiencies unparalleled with current microfluidics-based state of the art. In the method, bacteria-spiked blood sample is prepositioned close to the outer wall of a spiral microchannel using a viscoelastic sheath buffer. The blood cells will remain fully focused throughout the length of the channel while bacteria migrate to the inner wall for effective separation. Initially, particles of different sizes were used to investigate particle focusing and the separation performance of the spiral device. A separation efficiency of 96% for the 1 micrometer particles was achieved, while 100% of 3 micrometer particles were recovered at the desired outlet at a high throughput of 1 mL/min. Following, processing blood samples revealed a minimum of 1:2 dilution was necessary to keep the blood cells fully focus at the outer wall. In experiments involving bacteria spiked in diluted blood, viable E.coli were continuously separated at a total flow rate of 1 mL/min, with an efficiency between 82 to 90% depending on the blood dilution. Using a single spiral, it takes 40 minutes to process 1 mL of blood at a separation efficiency of 82% and 3 hours at 90% efficiency. To the best of our knowledge, this is the highest blood sample throughput per single microfluidic chip reported for the corresponding separation efficiency. As such, the label-free, passive and high throughput bacteria isolation method has a great potential for speeding up downstream phenotypic and molecular analysis of bacteria.

中文翻译：

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弹性惯性微流控技术从血液中分离高分辨率和高通量细菌

改进的样品前处理方法有可能满足快速周转败血症测试的巨大需求，这些测试能够尽早实施适当的抗微生物治疗。近年来，基于惯性和弹性惯性微流体的样品制备方法在生物颗粒分离应用中引起了极大的兴趣。然而，对于在血流感染中的应用，迄今为止，通过量和细菌分离效率受到限制。在这项工作中，我们首次报道了基于弹性-微微流体的细菌从血液中的分离，其通量和效率与当前基于微流体的现有技术无与伦比。在该方法中，使用粘弹性护套缓冲液将掺有细菌的血液样本预先放置在螺旋微通道的外壁附近。在细菌迁移到内壁进行有效分离的同时，血细胞将在通道的整个长度上保持完全聚焦。最初，使用不同大小的颗粒来研究颗粒聚焦和螺旋装置的分离性能。1微米颗粒的分离效率达到96％，而3微米颗粒的100％在所需出口以1 mL / min的高通量回收。随后，处理的血液样本显示必须保持至少1：2的稀释度才能使血细胞完全聚焦在外壁。在涉及稀释血液中掺入细菌的实验中，以1 mL / min的总流速连续分离出活的大肠杆菌，取决于血液稀释度，效率在82％到90％之间。使用单螺旋 以82％的分离效率处理1 mL血液需要40分钟，以90％的效率处理需要3小时。据我们所知，这是每个单微流控芯片报告的最高血样通量，具有相应的分离效率。因此，无标记，被动和高通量的细菌分离方法具有加快细菌下游表型和分子分析的巨大潜力。