Jung Han Sae, Jung Woo-Bin, Wang Jun, Abbott Jeffrey, Horgan Adrian, Fournier Maxime, Hinton Henry, Hwang Young-Ha, Godron Xavier, Nicol Robert, Park Hongkun, Ham Donhee
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Sci Adv. 2022 Jul 29;8(30):eabm6815. doi: 10.1126/sciadv.abm6815. Epub 2022 Jul 27.
pH controls a large repertoire of chemical and biochemical processes in water. Densely arrayed pH microenvironments would parallelize these processes, enabling their high-throughput studies and applications. However, pH localization, let alone its arrayed realization, remains challenging because of fast diffusion of protons in water. Here, we demonstrate arrayed localizations of picoliter-scale aqueous acids, using a 256-electrochemical cell array defined on and operated by a complementary metal oxide semiconductor (CMOS)-integrated circuit. Each cell, comprising a concentric pair of cathode and anode with their current injections controlled with a sub-nanoampere resolution by the CMOS electronics, creates a local pH environment, or a pH "voxel," via confined electrochemistry. The system also monitors the spatiotemporal pH profile across the array in real time for precision pH control. We highlight the utility of this CMOS pH localizer-imager for high-throughput tasks by parallelizing pH-gated molecular state encoding and pH-regulated enzymatic DNA elongation at any selected set of cells.
pH值控制着水中大量的化学和生物化学过程。密集排列的pH微环境将使这些过程并行化,从而实现对它们的高通量研究和应用。然而,由于质子在水中的快速扩散,pH值的定位,更不用说其阵列化实现,仍然具有挑战性。在这里,我们展示了皮升规模的水性酸的阵列定位,使用由互补金属氧化物半导体(CMOS)集成电路定义并操作的256个电化学电池阵列。每个电池由一对同心的阴极和阳极组成,CMOS电子器件以亚纳安分辨率控制它们的电流注入,通过受限电化学产生局部pH环境,即pH“体素”。该系统还实时监测整个阵列的时空pH分布,以实现精确的pH控制。我们通过在任何选定的一组细胞中并行化pH门控分子状态编码和pH调节的酶促DNA延伸,突出了这种CMOS pH定位成像仪在高通量任务中的实用性。