Exponential DNA amplification techniques are fundamental in ultrasensitive molecular diagnostics. These systems offer a wide dynamic range, but the quantification requires real‐time monitoring of the amplification reaction. Linear amplification schemes, despite their limited sensitivity, can achieve quantitative measurement from a single end‐point readout, suitable for low‐cost, point‐of‐care, or massive testing. Reconciling the sensitivity of exponential amplification with the simplicity of end‐point readout would thus break through a major design dilemma and open a route to a new generation of massively scalable quantitative bioassays. Here a hybrid nucleic acid‐based circuit design is introduced to compute a logarithmic function, therefore providing a wide dynamic range based on a single end‐point measurement. CELIA (Coupling Exponential amplification reaction to LInear Amplification) exploits a versatile biochemical circuit architecture to couple a tunable linear amplification stage – optionally embedding an inverter function – downstream of an exponential module in a one‐pot format. Applied to the detection of microRNAs, CELIA provides a limit of detection in the femtomolar range and a dynamic range of six decades. This isothermal approach bypasses thermocyclers without compromising sensitivity, thereby opening the way to applications in various diagnostic assays, and providing a simplified, cost‐efficient, and high throughput solution for quantitative nucleic acid analysis.

中文翻译：

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将指数放大与线性放大耦合进行终点定量分析

指数 DNA 扩增技术是超灵敏分子诊断的基础。这些系统提供了较宽的动态范围，但定量需要实时监测扩增反应。线性放大方案尽管灵敏度有限，但可以通过单个终点读数实现定量测量，适合低成本、现场护理或大规模测试。因此，协调指数扩增的灵敏度与终点读数的简单性将突破主要的设计困境，并为新一代大规模可扩展的定量生物测定开辟道路。这里引入了基于混合核酸的电路设计来计算对数函数，因此基于单端点测量提供了宽动态范围。 CELIA（将指数放大反应与线性放大耦合）利用多功能生化电路架构，以一锅式形式将可调线性放大级（可选地嵌入反相器功能）耦合到指数模块的下游。应用于 microRNA 的检测时，CELIA 提供飞摩尔范围内的检测限和 6 个十进制的动态范围。这种等温方法绕过热循环仪而不会影响灵敏度，从而为各种诊断分析中的应用开辟了道路，并为定量核酸分析提供了一种简化的、经济高效的高通量解决方案。