<italic style="font-style: italic">In situ</italic> chemical synthesis of DNA microarrays

YAN Han; XIAO Pengfeng; LIU Quanjun; LU Zuhong

doi:10.12211/2096-8280.2020-089

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In situ chemical synthesis of DNA microarrays

Invited Review | 更新时间：2025-03-20

- In situ chemical synthesis of DNA microarrays
- Synthetic Biology Journal Vol. 2, Issue 3, Pages: 354-370(2021)
- 作者机构：
  
  东南大学生物科学与生物医学工程学院，生物电子学国家重点实验室，江苏南京 210096
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2020-089
  CLC： Q81
- Received：21 December 2020，
  
  Revised：2021-04-09，
  
  Published：30 June 2021
- 稿件说明：
移动端阅览
闫汉，肖鹏峰，刘全俊，陆祖宏. DNA微阵列原位化学合成［J］. 合成生物学， 2021， 2（3）： 354-370

YAN Han， XIAO Pengfeng， LIU Quanjun， LU Zuhong. In situ chemical synthesis of DNA microarrays［J］. Synthetic Biology Journal， 2021， 2（3）： 354-370
闫汉，肖鹏峰，刘全俊，陆祖宏. DNA微阵列原位化学合成［J］. 合成生物学， 2021， 2（3）： 354-370 DOI： 10.12211/2096-8280.2020-089.

YAN Han， XIAO Pengfeng， LIU Quanjun， LU Zuhong. In situ chemical synthesis of DNA microarrays［J］. Synthetic Biology Journal， 2021， 2（3）： 354-370 DOI： 10.12211/2096-8280.2020-089.

摘要

高通量、快速、低成本DNA合成是合成生物学、DNA信息存储以及DNA芯片等前沿科技领域的重要核心技术。DNA微阵列原位化学合成方法是在亚磷酸酰胺固相化学合成原理的基础上，整合了微电子学、计算科学、分子生物学、光电化学和微纳加工等学科的相关技术，近30年来得到了迅速的发展和应用。DNA微阵列原位化学合成方法根据不同的碱基分配方式可以分为原位光刻法、光敏抗蚀层合成法、光致酸法、喷印合成法、软光刻合成法、电致酸法和压印法以及以这些技术为基础衍生的各种合成方法等。本文对上述不同的DNA微阵列原位化学合成方法及其技术特点进行阐述，并对未来DNA合成方法的发展趋势进行讨论和展望。合成通量和效率方面基于CMOS芯片的电致酸DNA原位化学合成技术在未来10年内将具备较大的发展空间，通过解决芯片上微电极间氢离子串扰问题，有望实现单片TB级的DNA快速低成本合成。

Abstract

High-throughput

rapid and low-cost DNA synthesis is an important core technology in the research fields such as synthetic biology

DNA storage and DNA chips. The in-situ chemical synthesis of DNA microarrays is based on the principle of solid-phase chemical synthesis of phosphorous acid amides

and integrates the relevant technologies of microelectronics

computational science

molecular biology

photo-electrochemistry and micro-nano processing. In the past 30 years

the technology has developed rapidly.

situ

chemical synthesis methods can be grouped into photolithography

photo-acid methods

electro-acid methods

printing methods and imprinting methods

etc

. based on their base allocation strategy. In this paper

we discuss the different

in-situ

chemical synthesis methods of DNA microarrays and their technical characteristics

as well as the potential development trends of DNA synthesis methods in the future. We believe that in terms of synthesis throughput and efficiency

the CMOS (Complementary Metal Oxide Semiconductor) chip-based in-situ chemical synthesis of electro-acid DNA has tremendous potential in the next decade. By solving the problem of hydrogen ion crosstalk between microelectrodes on the chip

it is expected that the rapid and low-cost synthesis of TB-level DNA can be accomplished on a single chip. As shown in the schematic diagram

the voltage of different areas of the DNA synthesis chip is controlled by computer to selectively deprotect the bases at different sites to achieve high-throughput parallel synthesis of different sequences of DNA. However

the bottleneck comes from the crosstalk between micro-electrodes due to acidic ion diffusion inside CMOS chip

which results in the limitation of synthetic capacity at the hundreds-of-megabyte level. After studying the behavior of hydrogen ion transport at the micrometer scale

the redesigning of CMOS chip with new materials and structures is suggested

aiming to suppress the ion diffusion between micro-electrodes and optimize the structure of microelectrodes and microfluidic channels of the chip and device. It is possible that the synthetic capacity of single chip could reach terabyte-level for CMOS-based in situ parallel DNA chemical synthesis with electro-acidified deprotection in the future

which will significantly accelerate the practical applications of synthetic biology and related technologies.

关键词

Keywords

references

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Key technologies for DNA storage: encoding, error correction, random access, and security

DNA information storage： bridging biological and digital world

Advances in technologies for de novo DNA synthesis， assembly and error correction

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Han Yan

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Quanjun Liu

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School of Biological Sciences and Biomedical Engineering， State Key Laboratory of Bioelectronics， Southeast University

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School of Physical Education and Health，Guangzhou University of Chinese Medicine

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In situ chemical synthesis of DNA microarrays

DOI：10.12211/2096-8280.2020-089

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