To many, the thought of handling microscale samples evokes an image of tedious manual pipetting. This time-consuming task can be largely replaced with automated manipulation of small samples. Automating sample handling can fill a growing need for applications like DNA sequencing, protein expression, biological assays, and rapid development of synthetic products.
Despite the initial monetary investment necessary to acquire these systems, automated sample handling brings distinct advantages. Laboratories working with small samples by hand face worker fatigue, reduced precision, and limitations on experimental throughput. In contrast, investing in automation can bring obvious benefits, from reduced repetitive motion injuries, greater reproducibility, and increased processing bandwidth. Additional benefits include savings from fewer wasted samples and reagents, as well as streamlined workflows. The capability to combine sample preparation with analytical instrumentation for fully automated synthesis and analysis is another advantage.
Common types of systems for handling small-scale samples
Likely the most recognizable form of automatic sample handling, pipette-based systems act as robotic pipetting platforms by dispensing solution from tips through contacting the deposition target. These pipette-based systems typically operate through either an air-cushion design for sample manipulation or with positive-displacement via pistons. For applications requiring higher accuracy and precision of low-volume samples, positive-displacement is preferable over the lower cost, lower precision air-cushion mechanism.
Similar to the pipette-based sample handling systems are those based on syringes and pins, both of which require contact between the dispensing device and intended end surface or solution. All three forms of the contact-based liquid manipulation platforms have the potential drawback of cross-contamination.
For laboratories that can afford to invest in an automated sample handling platform based on mechanisms other than pipetting, syringes, or pin dispensing, the alternatives may be better options when high precision and accuracy are paramount, if low- and sub-nanoliter samples are to be processed, or cross-contamination is a concern. A direct comparison of results based upon data collected from samples handled in a tip-based system and in an acoustic droplet ejection (ADE) platform found statistically different results between both datasets, with the ADE system appearing to provide more consistent values. ADE sample handling is also useful for rapid, microscale synthetic prototyping, which is how it was applied for automatic reaction scouting of isoquinoline synthetic building blocks in nanoliter droplets. Microscale acoustic manipulation has a wide range of potential applications because of its precise control, short dispensing time, and compatibility with high-capacity sample wells rendering the mechanism particularly appealing in bioassays.
Other forms of non-contact, high precision liquid handling are systems employing microfluidics, solenoid microvalves, and piezoelectric devices for aliquot ejection as some of the major classes of liquid manipulation technologies. Beyond simply a liquid transfer device, automation of sample handling with microfluidics offers the possibility of higher-order sample preparation, such as sample mixing, separations, and other preparatory steps for small sample sizes. Automated liquid handling with solenoid and piezoelectric devices has demonstrated accuracy and precision that is highly suitable for sensitive assays, even for picoliter and nanoliter volumes.