Biomolecular-Semiconductor Information Microsystems

我建议实现用于生物分子测量和分析的专用计算机芯片，特别是DNA测序。因为这些芯片将非常小，而且消耗的能量也很少，它们将使DNA测量仪（“测序仪”）变得更便宜、更小、更便携。实际上，这项研究将有助于使DNA测序对更广泛的用户来说更容易获得和负担得起，从而增强应用程序，如个性化医疗保健，生物分子环境传感，甚至下一代信息技术，如使用DNA本身的档案数据存储。******有三种芯片被提出，它们都是用于测序的一种形式，即单个DNA分子通过纳米级孔径（所谓的“纳米孔”传感器），这种动作会产生微小的DNA签名电流。对这种电流的分析揭示了DNA的构成，从而实现了测序。第一个定制芯片（模拟混合信号）负责放大和数字化从dna传感纳米孔中产生的极其微弱的特征电流。第二个（数字）定制芯片处理这些数字化测量信号，以计算被测量DNA由亚分子（“碱基”A、C、G、T）组成的序列，这一过程被称为“碱基调用”。第三个（数字）半定制芯片结合来自第一个和第二个芯片的信号，对组成测量DNA的碱基序列做出更准确的预测，从而使结果对详细的临床分析有用。******这三种芯片中的每一种都旨在显著推进DNA信号处理的最新技术。我对第一个芯片的研究重点是在不影响信号质量的情况下将其速度提高至少10倍（这样相对于竞争方法，它可以处理更多的DNA测量）。我的研究还打算制作第一个可编程芯片，并使其能够与纳米孔传感装置相互作用，以提高测序系统对制造和实验变化的适应性。我对第二个芯片的研究重点是将机器学习DNA序列分析推理算法集成到一个低于0.5 W的DNA碱基调用器中。迄今为止，还没有这种集成的碱基调用器存在于基于纳米孔的DNA测序器中。我对第三个芯片的研究集中在现场可编程门阵列（FPGA）硬件加速器上，该加速器与通用计算机一起工作，以提高DNA序列校正率100倍，同时大幅降低所需功耗。到目前为止，还没有这种基于硬件的加速器用于纳米孔测序校正的报道

I propose the realization of specialized computer chips for biomolecule measurement and analysis, specifically DNA sequencing. Because these chips will be very small and because they will consume very little power, they shall allow DNA measurement machines ("sequencers") to become less costly and small and portable too. In effect, this research will help make DNA sequencing much more accessible and affordable to a broader set of users thus empowering applications such as personalized healthcare, biomolecular environmental sensing, and even next-generation information technologies such as archival data storage using DNA itself.******Three chips are proposed, all for a form of sequencing whereby individual DNA molecules slip through a nano-scale aperture (a so-called “nanopore” sensor), an action that generates a minute signature-current of the DNA. An analysis of this current reveals the make-up of the DNA thus achieving sequencing. The first custom chip (analog mixed-signal) is responsible for amplifying and digitizing the extremely weak signature-currents emerging from the DNA-sensing nanopores. The second (digital) custom chip processes these digitized measurement signals to compute the sequence of sub-molecules (the "bases" A, C, G, T) that the measured DNA consists of, a process referred to as “basecalling”. The third (digital) semi-custom chip combines the signals from the first and second chip to make even more accurate predictions of the sequence of bases that make up the measured DNA, thus making the results useful for detailed clinical analysis.******Each of these three chips aims to significantly advance the state-of-the-art in DNA signal processing. My research into the first chip is focused on extending its speed (so that it can handle more DNA measurements relative to competing approaches) by at least 10X without compromising signal quality. My research also intends to make the first chip programmable and will also enable it to interact with the nanopore sensing apparatus in order to improve the sequencing system's adaptability to manufacturing and experimental variations. My research into the second chip is focused on integrating machine-learning DNA sequence analysis inference algorithms into a sub-0.5 W DNA basecaller. To date, no such integrated basecaller exists for nanopore-based DNA sequencers. My research into the third chip is focused on a field-programmable-gate-array (FPGA) hardware accelerator to work in conjunction with a general-purpose computer to increase the rate at which DNA sequences can be corrected by 100X with a substantial drop in required power consumption. To date, no such hardware-based accelerator for nanopore-based sequencing correction has been reported.**