Sulliger Marc, Ortega Arroyo Jaime, Quidant Romain
Nanophotonic Systems Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland.
Anal Chem. 2025 Feb 11;97(5):2736-2744. doi: 10.1021/acs.analchem.4c04731. Epub 2025 Jan 29.
Droplet-based microfluidics is a powerful tool for high-throughput analysis of liquid samples with significant applications in biomedicine and biochemistry. Nevertheless, extracting content-rich information from single picolitre-sized droplets at high throughputs remains challenging due to the weak signals associated with these small volumes. Overcoming this limitation would be transformative for fields that rely on high-throughput screening, enabling broader multiparametric analysis. Here we present an integrated optofluidic platform that addresses this critical point by combining advanced hyperspectral imaging with self-referencing and measurement automation. With this approach our platform achieves high temporal and spectral resolution with shot-noise limited performance, allowing for the label-free interrogation of single droplet contents. To demonstrate the platform's capabilities, we first exploit its high temporal and spectral resolution to study rapid dynamic changes in the composition of a heterogeneous population of nanoparticles. Second, leveraging the platform's shot-noise limited performance and using a model DNA-AuNP sensor, we detect target DNA sequences down to 250 pM, thereby showcasing the platform's compatibility with demanding sensing applications. Finally, through measurement automation, we demonstrate multiplexed sample monitoring over hours. These findings show that our optofluidic platform not only helps to close the current gap in high-throughput droplet analysis, but also significantly advances the potential for content-rich characterization, ultimately enhancing the scope and effectiveness of high-throughput screening methods.
基于微滴的微流控技术是一种用于液体样品高通量分析的强大工具，在生物医学和生物化学领域有着重要应用。然而，由于与这些小体积相关的信号较弱，在高通量下从单个皮升大小的微滴中提取丰富的信息仍然具有挑战性。克服这一限制对于依赖高通量筛选的领域将是变革性的，能够实现更广泛的多参数分析。在此，我们展示了一个集成光流体平台，该平台通过将先进的高光谱成像与自参考和测量自动化相结合，解决了这一关键问题。通过这种方法，我们的平台实现了具有散粒噪声限制性能的高时间和光谱分辨率，能够对单个微滴内容物进行无标记检测。为了展示该平台的能力，我们首先利用其高时间和光谱分辨率来研究异质纳米颗粒群体组成的快速动态变化。其次，利用该平台的散粒噪声限制性能并使用模型DNA-金纳米颗粒传感器，我们检测到低至250 pM的目标DNA序列，从而展示了该平台与苛刻传感应用的兼容性。最后，通过测量自动化，我们展示了数小时的多重样品监测。这些发现表明，我们的光流体平台不仅有助于弥合当前高通量微滴分析中的差距，而且还显著推进了丰富内容表征的潜力，最终提高了高通量筛选方法的范围和有效性。
