Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, United Kingdom.
Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15162-7. doi: 10.1073/pnas.1206055109. Epub 2012 Sep 4.
Ultrasonics offers the possibility of developing sophisticated fluid manipulation tools in lab-on-a-chip technologies. Here we demonstrate the ability to shape ultrasonic fields by using phononic lattices, patterned on a disposable chip, to carry out the complex sequence of fluidic manipulations required to detect the rodent malaria parasite Plasmodium berghei in blood. To illustrate the different tools that are available to us, we used acoustic fields to produce the required rotational vortices that mechanically lyse both the red blood cells and the parasitic cells present in a drop of blood. This procedure was followed by the amplification of parasitic genomic sequences using different acoustic fields and frequencies to heat the sample and perform a real-time PCR amplification. The system does not require the use of lytic reagents nor enrichment steps, making it suitable for further integration into lab-on-a-chip point-of-care devices. This acoustic sample preparation and PCR enables us to detect ca. 30 parasites in a microliter-sized blood sample, which is the same order of magnitude in sensitivity as lab-based PCR tests. Unlike other lab-on-a-chip methods, where the sample moves through channels, here we use our ability to shape the acoustic fields in a frequency-dependent manner to provide different analytical functions. The methods also provide a clear route toward the integration of PCR to detect pathogens in a single handheld system.
超声技术为在微流控芯片技术中开发复杂的流体操控工具提供了可能。在这里,我们通过在一次性芯片上进行图案化的声子晶格来展示对超声场进行塑形的能力,以执行复杂的流体操控序列,从而在血液中检测到啮齿动物疟疾寄生虫疟原虫。为了说明我们可用的不同工具,我们使用声场产生所需的旋转涡旋,以机械裂解一滴血液中的红细胞和寄生虫细胞。然后,我们使用不同的声场和频率来扩增寄生虫基因组序列,以加热样本并进行实时 PCR 扩增。该系统不需要使用裂解试剂或富集步骤,因此非常适合进一步集成到微流控芯片即时检测设备中。这种声学生物样品制备和 PCR 使我们能够在微升大小的血液样本中检测到约 30 个寄生虫,其灵敏度与基于实验室的 PCR 测试相同。与其他微流控芯片方法不同,样品在通道中移动,在这里我们利用我们以频率相关方式塑造声场的能力来提供不同的分析功能。这些方法还为在单个手持式系统中集成 PCR 以检测病原体提供了明确的途径。