Sikes Hadley D, Hansen Ryan R, Johnson Leah M, Jenison Robert, Birks John W, Rowlen Kathy L, Bowman Christopher N
Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309, USA.
Nat Mater. 2008 Jan;7(1):52-6. doi: 10.1038/nmat2042. Epub 2007 Oct 28.
Clinical and field-portable diagnostic devices require the detection of atto- to zeptomoles of biological molecules rapidly, easily and at low cost, with stringent requirements in terms of robustness and reliability. Though a number of creative approaches to this difficult problem have been reported, numerous unmet needs remain in the marketplace, particularly in resource-poor settings. Using rational materials design, we investigated harnessing the amplification inherent in a radical chain polymerization reaction to detect molecular recognition. Polymerization-based amplification is shown to yield a macroscopically observable polymer, easily visible to the unaided eye, as a result of as few as approximately 1,000 recognition events (10 zeptomoles). Design and synthesis of a dual-functional macromolecule that is capable both of selective recognition and of initiating a polymerization reaction was central to obtaining high sensitivity and eliminating the need for any detection equipment. Herein, we detail the design criteria that were used and compare our findings with those obtained using enzymatic amplification. Most excitingly, this new approach is general in that it is readily adaptable to facile detection at very low levels of specific biological interactions of any kind.
临床和现场便携式诊断设备需要快速、简便且低成本地检测阿托摩尔至zeptomole级别的生物分子,同时对稳健性和可靠性有严格要求。尽管已经报道了许多针对这一难题的创新方法,但市场上仍存在许多未满足的需求,尤其是在资源匮乏的地区。通过合理的材料设计,我们研究了利用自由基链式聚合反应中固有的扩增来检测分子识别。基于聚合的扩增显示,由于少至约1000次识别事件(10 zeptomole),就能产生肉眼易于观察到的宏观聚合物。设计和合成一种既能进行选择性识别又能引发聚合反应的双功能大分子,对于获得高灵敏度和无需任何检测设备至关重要。在此,我们详细介绍了所使用的设计标准,并将我们的研究结果与使用酶促扩增获得的结果进行比较。最令人兴奋的是,这种新方法具有通用性,因为它很容易适用于对任何种类的特定生物相互作用进行极低水平的简便检测。