Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, UCLA, Los Angeles, CA, USA.
Department of Bioengineering, UCLA, Los Angeles, CA, USA.
Nature. 2022 Nov;611(7936):570-577. doi: 10.1038/s41586-022-05408-3. Epub 2022 Nov 9.
Expanding our global testing capacity is critical to preventing and containing pandemics. Accordingly, accessible and adaptable automated platforms that in decentralized settings perform nucleic acid amplification tests resource-efficiently are required. Pooled testing can be extremely efficient if the pooling strategy is based on local viral prevalence; however, it requires automation, small sample volume handling and feedback not available in current bulky, capital-intensive liquid handling technologies. Here we use a swarm of millimetre-sized magnets as mobile robotic agents ('ferrobots') for precise and robust handling of magnetized sample droplets and high-fidelity delivery of flexible workflows based on nucleic acid amplification tests to overcome these limitations. Within a palm-sized printed circuit board-based programmable platform, we demonstrated the myriad of laboratory-equivalent operations involved in pooled testing. These operations were guided by an introduced square matrix pooled testing algorithm to identify the samples from infected patients, while maximizing the testing efficiency. We applied this automated technology for the loop-mediated isothermal amplification and detection of the SARS-CoV-2 virus in clinical samples, in which the test results completely matched those obtained off-chip. This technology is easily manufacturable and distributable, and its adoption for viral testing could lead to a 10-300-fold reduction in reagent costs (depending on the viral prevalence) and three orders of magnitude reduction in instrumentation cost. Therefore, it is a promising solution to expand our testing capacity for pandemic preparedness and to reimagine the automated clinical laboratory of the future.
扩大我们的全球检测能力对于预防和控制大流行病至关重要。因此,需要在分散环境中具有可访问性和适应性的自动化平台,这些平台能够高效地进行核酸扩增检测。如果基于当地病毒流行率的混合测试策略,那么混合测试可以非常高效;但是,它需要自动化、小样本量处理和当前大型、资本密集型液体处理技术无法提供的反馈。在这里,我们使用一群毫米大小的磁铁作为移动机器人代理(“ferrobots”),用于精确而稳健地处理磁化样本液滴,并根据核酸扩增测试实现高保真的灵活工作流程,从而克服这些限制。在一个手掌大小的基于印刷电路板的可编程平台上,我们展示了混合测试中涉及的众多实验室等效操作。这些操作由引入的正方形矩阵混合测试算法指导,以识别来自感染患者的样本,同时最大程度地提高测试效率。我们将这种自动化技术应用于临床样本中 SARS-CoV-2 病毒的环介导等温扩增和检测,其测试结果与片外获得的结果完全匹配。该技术易于制造和分发,如果将其用于病毒检测,可以将试剂成本降低 10-300 倍(取决于病毒流行率),并将仪器成本降低三个数量级。因此,这是扩大我们的大流行病防范检测能力并重新构想未来自动化临床实验室的有前途的解决方案。