Modeling Taylor dispersion injections: Determination of kinetic/affinity interaction constants and diffusion coefficients in label-free biosensing
Modeling Taylor dispersion injections: Determination of kinetic/affinity interaction constants and diffusion coefficients in label-free biosensing
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DOI：
10.1016/j.ab.2011.11.024
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发表时间：
2012-02-15
影响因子：
2.9
通讯作者：
Quinn, John G.
中科院分区：
文献类型：
--
作者：
Quinn, John G.
一种新的方法，基于泰勒分散已被开发，使分析物梯度滴定配体涂层表面的动力学/亲和性分析的相互作用，从最少的注射次数。泰勒分散注射产生超过四个数量级的浓度范围，并使分析物扩散系数能够可靠地估计为拟合结合相互作用模型时的拟合参数。基于有限元分析、Monte Carlo模拟和统计分析的数值模型用于比较泰勒分散法与标准固定浓度注射剂在参数相关性、参数误差空间的线性度以及全局与局部模型拟合方面的差异。当达到表面饱和时，观察到TDi曲线相对于标准固定浓度注射曲线的参数相关性急剧下降。在FCI中，相对于注射时间记录结合进展，而在TDi中，分析物梯度中编码的第二时间依赖性增加了分辨能力。这大大降低了所有参数之间的相互依赖性和对实验干扰的依赖性。当局部拟合模型参数时，TDis的性能仍与全局模型拟合相当，而固定浓度结合响应曲线产生不可靠的参数估计值。(C)2011 Elsevier Inc. All rights reserved.
A new method based on Taylor dispersion has been developed that enables an analyte gradient to be titrated over a ligand-coated surface for kinetic/affinity analysis of interactions from a minimal number of injections. Taylor dispersion injections generate concentration ranges in excess of four orders of magnitude and enable the analyte diffusion coefficient to be reliably estimated as a fitted parameter when fitting binding interaction models. A numerical model based on finite element analysis, Monte Carlo simulations, and statistical profiling were used to compare the Taylor dispersion method with standard fixed concentration injections in terms of parameter correlation, linearity of parameter error space, and global versus local model fitting. A dramatic decrease in parameter correlations was observed for TDi curves relative to curves from standard fixed concentration injections when surface saturation was achieved. In FCI the binding progress is recorded with respect to injection time, whereas in TDi the second time dependency encoded in the analyte gradient increases resolving power. This greatly lowers the dependence of all parameters on each other and on experimental interferences. When model parameters were fitted locally, the performance of TDis remained comparable to global model fitting, whereas fixed concentration binding response curves yielded unreliable parameter estimates. (C) 2011 Elsevier Inc. All rights reserved.