Bergkamp Max H, Cajigas Sebastian, van IJzendoorn Leo J, Prins Menno W J
Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AE Eindhoven, The Netherlands.
Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, 5612 AE Eindhoven, The Netherlands.
Lab Chip. 2023 Oct 10;23(20):4600-4609. doi: 10.1039/d3lc00410d.
Real-time monitoring-and-control of biological systems requires lab-on-a-chip sensors that are able to accurately measure concentration-time profiles with a well-defined time delay and accuracy using only small amounts of sampled fluid. Here, we study real-time continuous monitoring of dynamic concentration profiles in a microfluidic measurement chamber. Step functions and sinusoidal oscillations of concentrations were generated using two pumps and a herringbone mixer. Concentrations in the bulk of the measurement chamber were quantified using a solution with a dye and light absorbance measurements. Concentrations near the surface were measured using a reversible cortisol sensor based on particle motion. The experiments show how the total time delay of the real-time sensor has contributions from advection, diffusion, reaction kinetics at the surface and signal processing. The total time delay of the studied real-time cortisol sensor was ∼90 seconds for measuring 63% of the concentration change. Monitoring of sinusoidal cortisol concentration-time profiles showed that the sensor has a low-pass frequency response with a cutoff frequency of ∼4 mHz and a lag time of ∼60 seconds. The described experimental methodology paves the way for the development of monitoring-and-control in lab-on-a-chip systems and for further engineering of the analytical characteristics of real-time continuous biosensors.
对生物系统进行实时监测和控制需要芯片实验室传感器，这种传感器能够仅使用少量采样流体，以明确的时间延迟和精度准确测量浓度-时间曲线。在此，我们研究了微流体测量腔室中动态浓度曲线的实时连续监测。使用两个泵和一个人字形混合器产生浓度的阶跃函数和正弦振荡。使用含有染料的溶液和吸光度测量对测量腔室主体中的浓度进行定量。使用基于粒子运动的可逆皮质醇传感器测量表面附近的浓度。实验表明，实时传感器的总时间延迟来自平流、扩散、表面反应动力学和信号处理。所研究的实时皮质醇传感器测量63%浓度变化的总时间延迟约为90秒。对正弦皮质醇浓度-时间曲线的监测表明，该传感器具有低通频率响应，截止频率约为4 mHz，滞后时间约为60秒。所描述的实验方法为芯片实验室系统中监测和控制的发展以及实时连续生物传感器分析特性的进一步工程化铺平了道路。
