超声移液及微量移液技术进展和展望

doi:10.12211/2096-8280.2023-036

摘要/Abstract

摘要：

近年来，合成生物学、新药研究以及体外诊断等现代生物、医学技术的快速发展对微量移液技术的精准度、通量、成本等各方面提出了越来越高的要求。传统基于活塞原理的移液技术虽然可以做到自动化，通量可以很高，但是移液精度局限于亚微升级。基于电磁阀、压电驱动等移液技术可以大幅度提高移液精度，但是由于结构复杂，通量难以与活塞式移液技术相媲美。基于电场、磁场、激光等新型移液技术的移液精度可以实现纳升级和皮升级，但是这些技术主要基于微流控平台，针对一些特定应用，通用性差。此外，上述移液技术都需要使用吸头、毛细管、喷嘴等移液头，会与液体直接接触，存在移液头容易堵塞、液体残留、样品交叉污染的风险，而且移液头大都是一次性耗材，成本高，污染环境。非接触式超声移液技术是一种声镊技术，利用超声波声场调制的声辐射力实现对液滴的无接触式操控，无需一次性移液头辅助，无需与液体接触，且具有精度高、移液速度快等特点，是较为理想的精密微量移液技术，展现了重要的应用前景。本文对微量移液技术的发展和代表性研究进展进行了系统性介绍，重点介绍了非接触式超声移液技术的发展和研究进展，并分析讨论了微量移液技术值得关注的发展方向，比如高通量及高通用性的非接触式超声移液技术、智能化移液工作站，以及基于微流控平台的微量液体处理技术等。

关键词: 非接触式超声移液, 微量移液, 声辐射力, 声镊, 高精度, 高通量, 自动化

Abstract:

In recent years, the rapid development of modern biological and medical technologies, such as synthetic biology, new drug research, and in vitro diagnosis, has put forward increasingly high requirements on the precision, accuracy, throughput and cost of low-volume liquid transfer technology as the number of liquid samples increases but the volume of liquid samples decreases greatly. Although the traditional piston-based pipetting technology can achieve automation and high throughput, the pipetting precision is limited to sub-microliter, and it consumes a large amount of disposable pipette tips. The liquid transfer technologies based on solenoid valve and piezoelectric actuator can improve liquid transfer precision greatly, however, the throughput of these technologies are lower than pipetting technology due to their complex structures. The liquid transfer technologies based on electric field, magnetic field, and light can achieve high transfer precision of nanoliter and picoliter, but these technologies are mainly based on the microfluidic platform for some special applications. In addition, the tips such as the pipette tip, tubing, or nozzle used in the aforementioned liquid transfer technologies are in direct contact with the liquid, leading to the risks of tip blockage, liquid residue and sample cross-contamination. Moreover, the tips are mostly disposable, resulting in high cost and environmental pollution. Non-contact ultrasonic liquid transfer technology, using acoustic radiation force of focused ultrasonic wave to eject droplets from liquid surface, does not need disposable tips, and the ejected droplets do not contact with any other media except the liquid containers during the transfer process. The size of ejected droplets can be accurately controlled by adjusting the focus size and acoustic energy of ultrasound beam. The liquid transfer volume can be adjusted over a large range from nanoliter to picoliter with high precision. Due to its characteristics of fully contact-free, high precision and high transfer speed, non-contact ultrasonic liquid transfer technology shows great potential in biological and medical applications. In this paper, we introduce the development and representative progress of low-volume liquid transfer technology, with emphasis on the development and progress of non-contact ultrasonic liquid transfer technology. Finally the future trends of low-volume liquid transfer technology are analyzed and discussed, such as non-contact ultrasonic liquid transfer technology with high throughput and good versatility, intelligent liquid handling workstation, and low-volume liquid handling technology based on microfluidic platform.

Key words: non-contact ultrasonic liquid transfer, low-volume liquid transfer, acoustic radiation force, acoustic tweezers, high precision, high throughput, automation

中图分类号:

Q819

张志强, 张扬, 邱维宝, 郑海荣. 超声移液及微量移液技术进展和展望[J]. 合成生物学, 2023, 4(5): 916-931.

zhiqiang ZHANG, Yang ZHANG, Weibao QIU, Hairong ZHENG. Progress and prospect of ultrasonic liquid transfer and low-volume liquid transfer technology[J]. Synthetic Biology Journal, 2023, 4(5): 916-931.

图/表 7

图1 微量移液技术发展进程

Fig. 1 Development process of low-volume liquid transfer technology

图2 商业自动化移液工作站

Fig. 2 Commercial automated liquid handling workstations

图3 基于不同驱动力的液滴生成技术示意图

Fig. 3 Schematic diagrams of droplet ejection based on different driving force

图4 非接触式超声移液技术［88］（利用聚焦超声波的声辐射力实现微小尺寸液滴的无接触式操控）

Fig. 4 Non-contact ultrasonic liquid transfer technology[88](a) Schematic diagram of non-contact ultrasonic liquid transfer technology:using acoustic radiation force of focused ultrasonic wave to eject droplets from liquid surface; (b) Time sequences of droplet ejection from the surface of deionized water by acoustic radiation force

图5 基于不同超声换能器的超声移液技术示意图

Fig. 5 Schematic diagrams of ultrasonic liquid transfer technology based on different acoustic transducers

图6 两种移液系统

Fig. 6 Liquid handling system from two companies

表1 不同微量移液技术对比

Table 1 Comparison of different low-volume liquid transfer technologies

微量移液技术		原理	精度	通量	重复性	代表性应用领域	代表性工作
接触式移液	移液器	活塞式	亚微升～微升	低	中	生物、医学、化学等实验室科学研究	Marburg移液器
	自动化移液工作站	活塞式	亚微升～微升	高	高	合成生物学、药物筛选、PCR预处理、DNA测序	EpMotion系列，Biomek系列，Microlab STAR， Freedom EVO系列
	电磁阀移液	电磁阀驱动	纳升～微升	中	高	生物芯片点样	PixSys
	压电驱动移液	压电驱动	皮升～纳升	中	高	生物领域的样品处理，微型化分析，微阵列检测，制药生产	BioChip，PipeJet TM
	基于微流控平台的电、磁、光、声驱动液滴生成技术	电场/磁场/光辐射力、光致空化/声辐射力	皮升～纳升	中	高	基于微流控平台的体外诊断应用	[24,26-28,82,86]
非接触式移液	超声移液	声辐射力	皮升～纳升	中	高	药物研发、基因组学、合成生物学	Echo系列，Arrow系列

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