Digital microfluidic biochips have fueled a paradigm shift in implementing bench-top laboratory experiments on a single tiny chip, thus replacing costly and bulky equipment. However, because of imprecise fluidic functions, several volumetric split errors may occur during the execution of bioassays. Earlier approaches to error-correcting sample preparation addressed this problem by using a cyberphysical system yielding several drawbacks such as increased sample preparation cost and time, and uncertainty in assay completion time. In addition, error correction for only a single-target sample has been considered so far, although many assays require the production of multi-target samples. In this work, we present an error-free dilution technique that guarantees the correctness of the resulting concentration factor of a sample without performing any additional roll-back or roll-forward action. To the best of our knowledge, we are the first to present a solution strategy for tackling dispensing errors during sample preparation. We use micro-electrode-dot-array biochips that offer the advantages of manipulating fractional volumes of droplets (aliquots) for navigation, as well as mix-split operations. Instead of performing traditional mix-and-split steps with integral-volume droplets, we execute only an aliquoting-and-mix sequence using differential-size aliquots. Thus, all split operations, which are the main source of errors in conventional digital microfluidic biochips, are completely eliminated, and hence neither sensing nor any correcting action is needed, and further, no management of intermediate waste droplets is needed. Additionally, the procedure can be fully parallelized for accurately producing multiple dilutions of a sample. Experimental results corroborate the superiority of the proposed method in terms of error management, as well as sample preparation cost and time.

中文翻译：

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在 MEDA 生物芯片上进行稳健的多目标样品制备，避免产生废物

数字微流控生物芯片推动了在单个微型芯片上实施台式实验室实验的范式转变，从而取代了昂贵和笨重的设备。然而，由于不精确的流体功能，在执行生物测定期间可能会出现几个体积分割误差。早期的纠错样品制备方法通过使用网络物理系统解决了这个问题，但会产生一些缺点，例如样品制备成本和时间增加，以及测定完成时间的不确定性。此外，到目前为止，已经考虑过仅对单目标样本进行误差校正，尽管许多分析需要产生多目标样本。在这项工作中，我们提出了一种无差错稀释技术，无需执行任何额外的回滚或前滚操作即可保证所得样品浓度因子的正确性。据我们所知，我们是第一个提出解决样品制备过程中分配错误的解决方案策略的人。我们使用微电极点阵列生物芯片，它具有操纵液滴（等分试样）的分数体积以进行导航以及混合拆分操作的优势。我们没有使用积分体积液滴执行传统的混合和拆分步骤，而是使用不同大小的等分试样仅执行等分和混合序列。因此，作为传统数字微流控生物芯片中主要错误来源的所有拆分操作都被完全消除，因此，既不需要感测也不需要任何纠正措施，此外，也不需要对中间废物液滴进行管理。此外，该过程可以完全平行化，以准确产生样品的多个稀释度。实验结果证实了所提出方法在错误管理以及样品制备成本和时间方面的优越性。