Liquid handling is an integral part of many scientific workflows, from compound screening and genomic research to drug discovery and diagnostic testing. However, effectively and efficiently managing liquids in a lab setting can be fraught with complexities. Understanding some of the key challenges, solutions, and best practices around liquid handling is essential for any researcher looking to optimize their processes and improve the quality of their results.
The Complexities Of Liquid Handling In Scientific Research
Liquid Handling Errors
Liquid handling encompasses a broad range of techniques and technologies for manipulating small volumes of liquids, from manual pipetting to automated liquid handling systems. While automation has improved accuracy and precision, errors can still occur at multiple points in the liquid handling workflow. KNF is one of the leading manufacturers of precision liquid handling components and systems. Preventing errors requires an understanding of their potential causes.
Inaccurate Pipetting
One of the most basic sources of error is inaccurate and imprecise pipetting. This can result from using low-quality or uncalibrated pipettes, allowing air bubbles to enter the tip, or not pre-wetting the pipette tip. A good pipetting technique is critical for reproducible results. Always check pipette calibration and replace tips regularly.
Cross-Contamination
Carryover of liquids from one sample to another is a common problem. It can occur when using the same pipette tip for multiple samples or not adequately cleaning automated liquid handlers between samples. Prevent cross-contamination by using fresh tips for each sample and scheduling wash routines.
Evaporation
Evaporation can reduce sample volumes over time and skew results. Use sealed containers, keep samples cool, limit open-air exposure, and work quickly to minimize evaporation effects. For very small volumes, it may be necessary to add evaporation inhibitors.
Adhesion Loss
Some amount of liquid may stick to pipette tips and vessel walls instead of being fully transferred. This adhesion loss can impact accuracy. Choose pipette tips engineered for low retention and use coatings or surfactants in vessels to reduce sticking.
Precision And Sensitivity
Beyond just accuracy, precision and sensitivity are also crucial. Imprecise or insensitive liquid handling can mean the difference between detecting a key result and not. Utilize liquid handlers and pipettes capable of CV below 5% for reproducibility.
Optimizing Liquid Handling
Addressing those common sources of error requires optimizing protocols, techniques, and tools. Some key ways researchers can improve their liquid handling processes include:
Automate When Possible
Automated liquid handling systems significantly improve precision and accuracy over manual pipetting while also increasing throughput. Their programmability helps standardize protocols across the lab. Look for systems with features like adjustable tip spacing, nano-litre dispensing capabilities, and real-time tracking.
Select The Right Consumables
Not all pipette tips and labware are equal. Select consumables designed specifically for optimal liquid handling performance. Look for certified low retention and low binding options. Also, consider features like elongated tips for accessing deep well plates.
Follow Best Practices
Adhere to proven tips for manual pipetting, such as pre-wetting tips, avoiding air bubbles, and discarding used tips promptly. Also, implement good lab hygiene like scheduled washing routines. Create and follow standardized protocols.
Monitor Quality
Build quality control steps like routine audits, calibration checks, and testing for carryover. Track key performance metrics over time. This allows you to detect issues early.
Train And Validate Users
Improper technique is a major source of error. Provide comprehensive training for all pipette and liquid handler users, along with periodic refresher courses. Conduct periodic validations to ensure proper technique.
By taking a systematic approach to addressing accuracy, precision, contamination, sensitivity, and reproducibility, researchers can significantly improve the quality of their liquid handling.
Optimizing Workflows And Throughput
In addition to improving liquid handling results, researchers also face the challenge of efficiently handling large numbers of samples.
Key factors in optimizing workflow include:
- Parallel Processing: Multi-channel pipettes and plate handlers allow the performance of operations on multiple samples simultaneously. This parallel processing greatly speeds up workflows.
- Automation: Automated liquid handlers minimize the need for human intervention. Features like plate stacking and on-deck storage allow extended unattended operation.
- Assay Miniaturization: Reducing reaction volumes through miniaturized plates and nano-litre dispensing preserves scarce samples and reagents.
- Lab Organization: Careful lab organization and storage make samples easily accessible to avoid workflow bottlenecks.
- Software Integration: Software that seamlessly integrates liquid handling systems, data tracking, scheduling, and lab management optimizes operations.
By combining smart assay design and layout with automated, integrated systems, labs can achieve the high-throughput, high-quality results needed to advance their research.
Adapting To Changing Needs
Importantly, liquid handling needs to change over time as workflows evolve. Flexibility is essential. Look for automated systems that allow reconfiguration and expansion as needs change. Modular components that work across multiple systems also provide adaptability.
Conclusion
Liquid handling underpins key scientific processes like screening, NGS library prep, and sample preparation. Navigating its complexities requires researchers to be mindful of potential errors, implement optimized techniques and tools, and adapt to evolving needs. By taking a systematic approach, labs can ensure accurate, precise, and efficient liquid handling critical to impactful research.
