Abstract
Although microliter-scale liquid handling with a handheld pipette is a routine task, pipetting nanoliter-scale volumes is challenging due to several technical difficulties including surface tension, adhesion and evaporation effects. We developed a fully automated piezoelectric micropipette with a precision of < 1 nanoliter, improving the efficiency of imaging-based single-cell isolation to above 90%. This improvement is crucial when sorting rare or precious cells, especially in medical applications. The compact piezoelectric micropipette can be integrated into various (bio)chemical workflows. It eliminates plastic tubes, valves, syringes, and pressure tanks. For high-quality phase-contrast illumination of the sample, e.g., cells or tiny droplets, we constructed rings of LEDs arranged concentrically to the micropipette. The same device can be readily used for single-cell printing and nanoliter-scale droplet printing of reagents using either fluorescent or transparent illumination on a microscope. We envision that this new technology will shortly become a standard tool for single-cell manipulations in medical diagnostics, e.g., circulating tumor cell isolation.
Highlights
Liquid handling on the milliliter or microliter scale is a routine task in laboratories, e.g., with handheld pipettes
Dynamics of tiny droplets is dominated by surface tension over gravity if the size of the droplet is smaller than the capillary length
Dropletbased microfluidics (Guo et al 2012; Köster et al 2008; Agresti et al 2010; Brouzes et al 2009; Leung et al 2012) works with subnanoliter water droplets suspended in an oil environment
Summary
Liquid handling on the milliliter (ml) or microliter (μl) scale is a routine task in laboratories, e.g., with handheld pipettes. Handling volumes under 0.1 μl is challenging. Dynamics of tiny droplets is dominated by surface tension over gravity if the size of the droplet is smaller than the capillary length. Microfluidic chips A straightforward solution to handle tiny volumes of fluids is to use microfluidics with micrometer-sized channels to conduct aqueous solutions. Dropletbased microfluidics (Guo et al 2012; Köster et al 2008; Agresti et al 2010; Brouzes et al 2009; Leung et al 2012) works with subnanoliter water droplets suspended in an oil environment. A number of technical drawbacks of currently available microfluidics have appeared (Leung et al 2012). These chips are very sensitive to the solid contamination of the medium. It is challenging to achieve the proper stability of the flow rate, not to mention transient effects before and
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