Research On Noncontact Liquid Dispensing Technology And System

In biomedical areas, such as protein crystallization, drug discovery, DNA sequencing, Single nucleotide polymorphism (SNP) genotyping and medical diagnostics, thousands of reagents with different viscosities need to be dispensed in submicroliter range. With the development of HTS, the sample volumes should be reduced to increase the screening chance with a given amount of sample, and it is not efficient to dispense accurately, quickly in submicroliter range with manual dispenser. This leads to the developments of automated liquid handling instruments that can transfer submicroliter volumes of fluid, which is contributive for enhance experiment conditions in biomedical areas.Sponsored by the National High Technology Research and Development Program of China (863 Program)"micro bio material dispensing technology for high throughput screening"(No.2007AA04Z311) and"research on precision piezo pump with flow sensor"(No.2007AA04Z336), an automated non contact liquid handling system that can accurately dispense desired volume reagents with a large range of viscosities was developed. This paper focuses on dispensing monism, flow sensing during dispensing process and the closed-loop control strategy.For liquid dispensing process analyses, in order to understand the droplet breakup process in more detail, make dispensing droplet fall off from the nozzle successfully and ensure accuracy and reproducibility for most of the reagent, CFD models were developed to simulate the reagent dispensing process. Analyses results explain how these parameters, such as the system pressure, liquid viscosity, density, surface tension, the size of nozzle and desired dispensing volume, affect the dispensing process, which is useful for choosing the right system pressure, suitable nozzle and appropriate control strategy in the automated liquid dispensing system.Thousands of reagents with different viscosities need to be transferred or dispensed in HTS. In order to enhance dispensing accuracy and reliability of liquid-handling robotic instruments, measurement of submicroliter flow rate is required to provide closed-loop control for accurately dispensing liquids with a large range of viscosities. So, a high-speed liquid flow sensor based on the measurement of the pressure difference across a flow restriction is presented. In this paper, the design, fabrication and measurement of this flow sensor were discussed in detail.For closed-loop control strategy study, a compound intelligent control strategy that combines the advantages of residual volume compensation method with the robustness of fuzzy logic controller is proposed. In our system, the integration of a custom high-speed MEMS flow sensor and using of a compound intelligent control strategy make it possible to self-adjust the open time of the solenoid vale and the system pressure to accurately dispense desired volume reagents with a large range of viscosities. The system could find appropriate valve open-time through only one pre-dispensing cycle without manual calibration, and could constantly monitor and correct the dispense process to make this system immune to sample viscosity, pressure fluctuation and some other disturbances.An automated valved based muti-channel liquid handling system was developed, and it could dispense submicroliter reagent accurately with closed-loop control method. The dispensed volume is modulated by altering the open time of the micro solenoid valve and the system pressure. The novel flow-through design ensures that the reagent doesn't flow through solenoid valve, and the valve will not be clogged easily. A gas tap is introduced to separate the system fluid and reagent, which reduce contaminating. In our system, the integration of a custom high-speed MEMS flow sensor and using of a compound intelligent control strategy make it possible to self-adjust the open time of the solenoid vale and the system pressure to accurately dispense desired volume reagents with a large range of viscosities and detect air bubbles or nozzle clogs in real time, which enhance the system reliability.Finally, experiment was carried out with different reagents and volumes. The 96-well dispensing operation with one channel was finished in 8.5 S. The repetitive precision of the dispense system was evaluated by the coefficient of variance. From the experiment results we can see that coefficient of variance (CV) has been shown to be below 3CV% at 1μl and approach 6CV% at 100 nl. It indicates that this liquid dispensing system still could dispense desired volume reagent accurately automatically when reagent or demand volume change. It meets for the requirement of automated liquid handling in submicrolitet accurately and quickly, which promotes the development of biomedical technology.