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      Low-volume liquid handling

      Low-volume liquid handling involves liquid volume transfers less than 2 µL. It is firmly established in compound management and screening workflows and increasingly adopted in other application areas, as laboratories strive to maximize their research output by miniaturizing assays, reducing reagent costs and increasing throughput. It is a technically demanding application that is not compatible with air displacement pipettes and liquid handlers. Therefore, many drug discovery laboratories have invested in dedicated low volume instruments to complement their existing liquid handling infrastructure.

      Low volume liquid handling for compound management, screening, and validation workflows

      Compound management, screening and validation workflows usually comprise four distinct low-volume liquid handling operations: 

      • cherry picking: to re-array relevant compounds from library source plates or tubes
      • plate reformatting: to work across 96-, 384-, and 1,536-well plate formats 
      • serial- or direct dilution: for dose-response experiments
      • plate stamping: to create assay-ready plate replicates

      Although acoustic droplet ejection and digital dispensers are undoubtedly popular choices to create compound dilution series, they still rely on upstream liquid handling steps to cherry pick compounds and transfer them to specialized source plates or cassettes. While it is possible to create multiple, assay-ready plates from a single reagent source plate, the process can be laborious.

      Low-volume, positive displacement liquid handlers such as the mosquito LV and mosquito X1 are notable alternatives (and complements) to acoustic and digital dispensers and offer their own unique range of benefits

      • extremely low dead volumes from just 0.5 μL per well
      • mosquito LV: serial dilution, plate reformatting, plate stamping, acoustic source plate creation capability in a single instrument
      • mosquito X1: versatile, low volume cherry picking from plates or tubes

       

      Assay miniaturization

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      With a shift towards more physiological models of disease (e.g. 3D cell cultures) and new technologies to interrogate disease biology (e.g. CRISPR-Cas9 gene editing, next-generation sequencing) the cost of assay reagents has increased significantly. Assay miniaturization is a crucial approach to lower reagent costs. Transitioning an assay from 96- to 384-well plates typically enables greater than 4-fold reagents savings, whereas a transition from 96-well to 1,536-well plates reduces reagent costs around 10-fold. These cost-efficiencies can be instrumental in enabling higher value research, increasing project output, and improving return on investment for laboratories. Low-volume positive displacement instruments such as the mosquito liquid handler and dragonfly® discovery dispenser are ideal tools for the accurate and precise setup of miniaturized assays. The technology enables researchers to maximise the value of expensive reagents without compromising on the quality or numbers of assays.

      FAQs

      Most assay classes (biochemical, cell-based and genomics assays) can be miniaturized to at least 384- if not 1,536-well plate formats. With low assay volumes, it is essential to mitigate the effects of evaporation to ensure consistently high assay quality metrics. This outcome can be achieved primarily through dispense speed, active or passive cooling, and evaporation barriers.

      It depends. Serial dilutions are quicker and easier to set up than direct dilutions. As each dilution point depends on the previous step, there is a risk of accumulating significant errors. Users must ensure the liquid handling performance of their instruments meets strict quality metrics when choosing this method.

      In a direct dilution series, all points are set up independently. While this process removes the risks of cumulative errors, no single instrument has the dynamic range required to set up a 3-4 log dilution series. Users therefore need to prepare and utilize intermediate dilutions.

      Small liquid volumes are prone to static interference that can cause liquid droplets to bounce or deflect on the plate. Contact liquid handlers tend not to suffer from static issues, as the droplet has little opportunity to deflect in contact mode.

      Non-contact dispensers may see issues that are typically more pronounced in the nanoliter dispense range and in very dry environments (water molecules diminish charge build up).

      If static interference is of concern, researchers can use a variety of tools such as ionising fans or anti-static guns to remove charge build up. In some instances, simply resting a microplate on a wet paper towel for a few minutes can be sufficient to minimize static effects.

      Related Products

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      dragonfly® discovery

      dragonfly discovery enables innovative, low volume reagent dispensing across a broad range of applications including genomics​, assay development, and 3D cell cultures. Highly repeatable and accurate low volume dispensing, rapid large volume dispensing, and ultra-low dead volumes allow researchers to minimize reagent costs, save time, and standardize assays for superior quality data.

      explore dragonly discovery

      mosquito® X1

      mosquito X1 offers precision low volume sampling of any individual well in any plate, using unique positive displacement pipetting technology. Its hit picking capability makes mosquito X1 perfectly suited for high throughput screening (HTS) hit confirmation and secondary profiling, as well as high throughput sample normalization and synthetic biology (DNA assembly).

      explore mosquito X1
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      mosquito® LV

      mosquito LV simplifies assay miniaturization within automated, high throughput settings. The easy to use instrument enables researchers to benefit from the significant time and reagent savings of minimal dead volumes (under 0.3 μL) and maximize return on research investment.

      explore mosquito LV

      Meet our Field Application Scientists

      Our Field Application Scientists will help you to advance your research goals throughout the life of your instrument, optimizing for the applications you need and harnessing its full potential. As specialists in a range of disciplines from structural biology to genomics, the team ensures that the protocols for your applications are scientifically robust, giving you the confidence to pursue novel approaches.  Working closely with customers, Field Application Scientists eliminate bottlenecks and streamline workflows to enable successful research outcomes.

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