Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London, WC1E 6BT, UK.
Paul Scherrer Institut, Villigen, PSI CH-5232, Switzerland.
Nat Commun. 2019 Aug 9;10(1):3594. doi: 10.1038/s41467-019-11604-z.
The selective amplification of DNA in the polymerase chain reaction is used to exponentially increase the signal in molecular diagnostics for nucleic acids, but there are no analogous techniques for signal enhancement in clinical tests for proteins or cells. Instead, the signal from affinity-based measurements of these biomolecules depends linearly on the probe concentration. Substituting antibody-based probes tagged for fluorescent quantification with lasing detection probes would create a new platform for biomarker quantification based on optical rather than enzymatic amplification. Here, we construct a virus laser which bridges synthetic biology and laser physics, and demonstrate virus-lasing probes for biosensing. Our virus-lasing probes display an unprecedented > 10,000 times increase in signal from only a 50% increase in probe concentration, using fluorimeter-compatible optics, and can detect biomolecules at sub-100 fmol mL concentrations.
聚合酶链反应中的 DNA 选择性扩增用于使核酸的分子诊断中的信号呈指数级增长,但在蛋白质或细胞的临床检测中没有类似的信号增强技术。相反,这些生物分子基于亲和力的测量的信号与探针浓度呈线性关系。用激光检测探针代替基于抗体的标记探针进行荧光定量,将为基于光学而不是酶扩增的生物标志物定量创建一个新平台。在这里,我们构建了一个将合成生物学和激光物理联系起来的病毒激光,并展示了用于生物传感的病毒激光探针。我们的病毒激光探针在使用荧光计兼容的光学器件时,仅将探针浓度提高 50%,就可使信号提高超过 10,000 倍,并且可以在亚 100 fmol mL 的浓度下检测生物分子。