Rapid, low-cost, and multiplexed biomolecule detection is an important goal in the development of effective molecular diagnostics. Our recent work has demonstrated a microfluidic biochip device that can electrically quantitate a protein target with high sensitivity. This platform detects and quantifies a target analyte by counting and capturing micron-sized beads in response to an immunoassay on the bead surface. Existing microparticles limit the technique to the detection of a single protein target and lack the magnetic properties required for separation of the microparticles for direct measurements from whole blood. Here, we report new precisely engineered microparticles that achieve electrical multiplexing and adapt this platform for low-cost and label-free multiplexed electrical detection of biomolecules. Droplet microfluidic synthesis yielded highly-monodisperse populations of magnetic hydrogel beads (MHBs) with the necessary properties for multiplexing the electrical Coulter counting on chip. Each bead population was designed to contain a different amount of the hydrogel material, resulting in a unique electrical impedance signature during Coulter counting, thereby enabling unique identification of each bead. These monodisperse bead populations span a narrow range of sizes ensuring that all can be captured sensitively and selectively under simultaneously flow. Incorporating these newly synthesized beads, we demonstrate versatile and multiplexed biomolecule detection of proteins or DNA targets. This development of multiplexed beads for the electrical detection of biomolecules, provides a critical advancement towards multiplexing the Coulter counting approach and the development of a low cost point-of-care diagnostic sensor.

中文翻译：

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使用电性不同的水凝胶珠快速、多重检测生物分子。

快速、低成本、多重生物分子检测是开发有效分子诊断的一个重要目标。我们最近的工作展示了一种微流体生物芯片装置，可以高灵敏度地电定量蛋白质靶标。该平台通过计数和捕获微米级的珠子来检测和量化目标分析物，以响应珠子表面的免疫测定。现有的微粒将该技术限制为检测单个蛋白质靶标，并且缺乏分离微粒以从全血中直接测量所需的磁性。在这里，我们报告了新的精确设计的微粒，可以实现电多重检测，并使该平台适用于生物分子的低成本和无标记多重电检测。液滴微流体合成产生了高度单分散的磁性水凝胶珠 (MHB) 群，具有在芯片上进行多重电 Coulter 计数所需的特性。每个珠子群体被设计为包含不同数量的水凝胶材料，从而在库尔特计数期间产生独特的电阻抗特征，从而能够对每个珠子进行唯一识别。这些单分散珠群的尺寸范围很窄，确保在同时流动的情况下可以灵敏且选择性地捕获所有珠群。结合这些新合成的珠子，我们展示了蛋白质或 DNA 靶标的多功能和多重生物分子检测。用于生物分子电检测的多重珠子的开发，为多重 Coulter 计数方法和低成本即时诊断传感器的开发提供了关键的进步。