Nanopipette: A high-precision portable programmable instrument for nanoliters to milliliters liquid handling.

The increasing emphasis on portability and miniaturization in biomedical analysis and detection necessitates higher accuracy and applicability in handling sample reagents. In this study, we propose a high-precision portable programmable nanopipette based on pneumatic drop-on-demand and gas displacement pipetting techniques. The nanopipette employs programmable electropneumatic regulators and solenoid valves for precise control over air pressure, air pulse duration, and the number of air pulses, enabling accurate dispensing of specific liquid volumes. The nanopipette provides both discrete and continuous dispensing modes. In the discrete mode, it employs a single droplet as the minimum unit, allowing for precise dispensing of sub-microliter liquids (≤500 nL) by accumulating uniformly sized droplets. Conversely, the continuous mode enables the rapid dispensing of larger volume liquids (>500 nL) through continuous gas displacement. Thanks to the two dispensing modes, the nanopipette can handle a broad range of dispensing volumes, spanning six orders of magnitude (from 3 nL to 1 mL), with a minimum volume increment of 1 nL. Through validation using two characterization methods, the nanopipette demonstrates systematic errors (random errors) ranging from − 0.5% to − 3.6% (± 0.9% to ± 4.4%), surpassing the performance of existing commercial micropipettes. In proof-of-concept experiments involving extensive dilution and quantitative analysis of drug toxicity, the nanopipette efficiently simplified experimental procedures (from multiple dilutions to single-step dilution), minimized reagent consumption (from 22 mL to 500 μL), and produced highly accurate and reliable experimental results. These findings highlight the applicability and potential value of the nanopipette in the field of biomedical research. [Display omitted] • A high-precision, wide volume range nanopipette based on drop-on-demand technique and gas displacement pipetting technique. • Nanopipette enables liquid handling within the range of 3 nL to 1 mL, with a minimum volume increment of 1 nL. • The biocompatibility and applicability of nanopipette have been demonstrated in biomedical experiments. [ABSTRACT FROM AUTHOR]