Zimmermann Martin, Delamarche Emmanuel, Wolf Marc, Hunziker Patrick
University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
Biomed Microdevices. 2005 Jun;7(2):99-110. doi: 10.1007/s10544-005-1587-y.
Microfluidics are emerging as a promising technology for miniaturizing biological assays for applications in diagnostics and research in life sciences because they enable the parallel analysis of multiple analytes with economy of samples and in short time. We have previously developed microfluidic networks for surface immunoassays where antibodies that are immobilized on one wall of a microchannel capture analytes flowing in the microchannel. This technology is capable of detecting analytes with picomolar sensitivity and from sub-microliter volume of sample within 45 min. This paper presents the theoretical modeling of these immunoassays where a finite difference algorithm is applied to delineate the role of the transport of analyte molecules in the microchannel (convection and diffusion), the kinetics of binding between the analyte and the capture antibodies, and the surface density of the capture antibody on the assay. The model shows that assays can be greatly optimized by varying the flow velocity of the solution of analyte in the microchannels. The model also shows how much the analyte-antibody binding constant and the surface density of the capture antibodies influence the performance of the assay. We then derive strategies to optimize assays toward maximal sensitivity, minimal sample volume requirement or fast performance, which we think will allow further development of microfluidic networks for immunoassay applications.
微流控技术正在成为一种很有前景的技术，可将生物检测小型化，用于诊断和生命科学研究，因为它能够在节省样品且短时间内对多种分析物进行并行分析。我们之前开发了用于表面免疫检测的微流控网络，其中固定在微通道一侧壁上的抗体捕获在微通道中流动的分析物。该技术能够以皮摩尔灵敏度在45分钟内从亚微升体积的样品中检测分析物。本文介绍了这些免疫检测的理论模型，其中应用有限差分算法来描述分析物分子在微通道中的传输（对流和扩散）作用、分析物与捕获抗体之间的结合动力学以及检测中捕获抗体的表面密度。模型表明，通过改变微通道中分析物溶液的流速，可以极大地优化检测。该模型还显示了分析物 - 抗体结合常数和捕获抗体的表面密度对检测性能的影响程度。然后，我们推导了优化检测以实现最大灵敏度、最小样品体积要求或快速检测性能的策略，我们认为这将有助于进一步开发用于免疫检测应用的微流控网络。
