Automated Sample Preparation

Automated Sample Preparation with PAL System

The Key to Reliable LC/MS and GC/MS Data

The increasing sensitivity of modern mass spectrometry (MS) instruments demands standardized and automated sample preparation to ensure the integrity of analytical data [1]. PAL System offers a robust solution by automating critical sample preparation steps, thereby significantly minimizing human error and maximizing data quality for both liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) workflows. This automation is crucial for obtaining reliable results, especially in demanding fields like metabolomics, proteomics, and clinical diagnostics [2]. Our robotic platform can be used as a stand-alone sample handler, integrated in all major Chromatography Data Systems (CDS), or can be built into other products (see our OEM partnerships).

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The Pitfalls of Manual Sample Preparation

The Pitfalls of Manual Sample Preparation

Traditional manual sample preparation methods are inherently susceptible to variability. Studies have shown that even minor inconsistencies in pipetting, extraction, or handling can introduce significant errors, potentially obscuring true biological variations and compromising the reliability of downstream analyses [3], [4], [5]. This makes it challenging to differentiate genuine signals from artifacts introduced during the preparation process, impacting the validity of research and diagnostic outcomes.

PAL System: Precision Automation for Consistent Results

PAL System: Precision Automation for Consistent Results

The PAL System provides a versatile and automated platform for comprehensive sample preparation and seamless sample introduction into LC/MS and GC/MS systems. By automating key steps, the PAL System significantly reduces the risk of human error, leading to more consistent and reproducible results across diverse sample types, experimental batches, and even between different laboratories [6], [7], [8]. This enhanced reproducibility is essential for robust data generation and reliable scientific conclusions.

 

Various pills scattered across a blue background. Highlighting the multitude of applications related to automation and sample preparation in the clinical field, i.e., blood analyses, bacterial identifications or general lipidomics/metabolomics for precision medicine.
Various pills scattered across a blue background. Highlighting the multitude of applications related to automation and sample preparation in the clinical field, i.e., blood analyses, bacterial identifications or general lipidomics/metabolomics for precision medicine.

Clinical Diagnostics

Accelerate Precision Medicine with PAL System

Automate critical sample preparation for rapid, accurate, and reliable diagnostic tools, essential for precision medicine. Tackle the bottlenecks of manual processes, improve reproducibility and free up technician time.

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Greens, such as leaves in a petri dish that are representative of the various environmental monitoring applications, e.g., PFAS analysis or pesticide monitoring.
Greens, such as leaves in a petri dish that are representative of the various environmental monitoring applications, e.g., PFAS analysis or pesticide monitoring.

Environmental Monitoring

Advanced Automated Analysis for a Healthier Planet

Meet the demands of global environmental challenges with PAL System's automated solutions for efficient and reliable analysis. Ideal for complex matrices and trace-level contaminants, including online SPE, uSPE and SPME Arrow for PFAS Analysis. When it comes to protecting our planet, the sky's the limit for what we can achieve with advanced automation.

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Strawberries in front of a a yellow background, representative of the various food and food safety applications.
Strawberries in front of a a yellow background, representative of the various food and food safety applications.

Food Safety

Ensure Consumer Confidence with Automated Prep

Rigorous food testing requires accuracy and efficiency. The PAL System automates key sample preparation steps, enhancing throughput for contaminant detection and authenticity verification. Key applications include automated Multi-Residue Pesticide Analysis using QuEChERS. Ensuring a safe food supply is a top priority, and with PAL System, the sky's the limit for quality control.

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Several lined up brains representative of the various fields of life science and biology.
Several lined up brains representative of the various fields of life science and biology.

Life Science

Automate -Omics Sample Prep for Faster Discovery.

Overcome the bottlenecks of manual sample preparation in genomics, proteomics, metabolomics, and drug discovery. The PAL System automates crucial steps, empowering researchers to accelerate discovery, including automated sample prep for Lipidomics. In the quest for scientific breakthroughs, the sky's the limit with the power of automated sample preparation.

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Versatile Sample Preparation Techniques

Mastering Complexity from Liquid Handling to Micromethods

The PAL System offers a comprehensive and automated suite of sample preparation techniques, seamlessly integrating both well-established methodologies and innovative micromethods to address a wide spectrum of analytical challenges. This commitment extends to supporting Green Analytical Chemistry principles by significantly minimizing solvent consumption and waste generation [9], [10].

 

 

 

PAL Solutions: Your Dedicated Partner for Complete Workflow Automation

PAL Solutions: Your Dedicated Partner for Complete Workflow Automation

Looking for a truly tailored and fully automated solution for your unique analytical challenges?

Based in the USA, PAL Solutions goes beyond standard product offerings to provide comprehensive, end-to-end services.

Our experienced team of application scientists and engineers collaborates closely with you to design, develop, and implement fully automated workflows. From the initial consultation and meticulous method development to seamless system configuration, expert installation, and ongoing support, we are committed to ensuring optimal performance and efficiency in your laboratory.

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PAL Newsroom

Explore articles, videos, interviews and more all around analytical chemistry and automation.

Discover what is happening in the field of metabolomics, proteomics and other -omics disciplines.

Visit the PAL Newsroom

Unlock the Full Potential of Your PAL System

We are dedicated to ensuring you achieve optimal results with your PAL System. Explore our comprehensive collection of resources, meticulously designed to help you streamline your workflows, effectively troubleshoot any challenges, and stay informed about the latest advancements in automated sample preparation. From in-depth application notes showcasing real-world examples to expert-led webinars providing valuable insights, we offer the information you need to maximize your investment and generate reliable data.

Explore our curated selection of resources below. Whether you are seeking specific application notes, detailed technical information, or expert advice in the form of webinars and presentations, you will find valuable content here:

References

[1]       G. Lippi, A. Von Meyer, J. Cadamuro, and A. M. Simundic, “PREDICT: A checklist for preventing preanalytical diagnostic errors in clinical trials,” Clin Chem Lab Med, vol. 58, no. 4, pp. 518–526, 2020, doi: 10.1515/cclm-2019-1089.

[2]       W. B. Dunn et al., “Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry,” Nat Protoc, vol. 6, no. 7, pp. 1060–1083, Jun. 2011, doi: 10.1038/nprot.2011.335.

[3]       D. L. S. Ferreira et al., “The effect of pre-analytical conditions on blood metabolomics in epidemiological studies,” Metabolites, vol. 9, no. 4, 2019, doi: 10.3390/metabo9040064.

[4]       V. L. Stevens, E. Hoover, Y. Wang, and K. A. Zanetti, “Pre-analytical factors that affect metabolite stability in human urine, plasma, and serum: A review,” 2019. doi: 10.3390/metabo9080156.

[5]       R. González-Domínguez, Á. González-Domínguez, A. Sayago, and Á. Fernández-Recamales, “Recommendations and best practices for standardizing the pre-analytical processing of blood and urine samples in metabolomics,” Metabolites, vol. 10, no. 6, pp. 1–18, 2020, doi: 10.3390/metabo10060229.

[6]       A. Schürmann, C. Crüzer, V. Duss, R. Kämpf, T. Preiswerk, and H.-J. Huebschmann, “Automated micro-solid-phase extraction clean-up and gas chromatography-tandem mass spectrometry analysis of pesticides in foods extracted with ethyl acetate,” Anal Bioanal Chem, Nov. 2023, doi: 10.1007/s00216-023-05027-5.

[7]       A. Kremser and I. Duisburg, “Advances in Automated Sample Preparation for Gas Chromatography: Solid-Phase Microextraction, Headspace-Analysis, Solid-Phase Extraction,” 2016.

[8]       S. Dugheri et al., “Advanced Solid-Phase Microextraction Techniques and Related Automation: A Review of Commercially Available Technologies,” 2022, Hindawi Limited. doi: 10.1155/2022/8690569.

[9]       G. Peris-Pastor, C. Azorín, J. Grau, J. L. Benedé, and A. Chisvert, “Miniaturization as a smart strategy to achieve greener sample preparation approaches: A view through greenness assessment,” TrAC Trends in Analytical Chemistry, p. 117434, Jan. 2023, doi: 10.1016/j.trac.2023.117434.

[10]     F. A. Esteve-Turrillas, S. Garrigues, and M. de la Guardia, “Green extraction techniques in green analytical chemistry: A 2019–2023 up-date,” TrAC Trends in Analytical Chemistry, vol. 170, p. 117464, Jan. 2024, doi: 10.1016/j.trac.2023.117464.

[11]     M. N. Wieczorek, W. Zhou, H. H. Jeleń, and J. Pawliszyn, “Automated sequential SPME addressing the displacement effect in food samples,” Food Chem, p. 138093, Nov. 2023, doi: 10.1016/j.foodchem.2023.138093.

[12]     A. Kremser, M. A. Jochmann, and T. C. Schmidt, “PAL SPME Arrow - Evaluation of a novel solid-phase microextraction device for freely dissolved PAHs in water,” Anal Bioanal Chem, vol. 408, no. 3, pp. 943–952, Jan. 2016, doi: 10.1007/s00216-015-9187-z.

[13]     D. Michiu, M. Tofană, S. A. Socaci, E. Mudura, L. C. Salanță, and A. C. Fărcaş, “Optimization of ITEX/GC-MS method for beer wort volatile compounds characterisation,” 2012. [Online]. Available: http://

 

FAQs

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Automating your sample preparation with the PAL System addresses the most common challenges in the analytical lab. Key benefits include:

  • Higher Throughput: Maximizes instrument uptime with unattended, 24/7 operation.

  • Improved Data Quality: Reduces manual errors, leading to greater precision, reproducibility, and more reliable results.

  • Enhanced Lab Safety: Minimizes human exposure to hazardous solvents and chemicals.

  • Full Traceability: Every step in the process is electronically logged, ensuring a complete and auditable sample history.

The PAL System is a robotic platform for automated sample preparation in analytical laboratories. With a modular "Tool Box" design and over 70,000 installations worldwide, it is a highly flexible and reliable solution that can be configured for simple injections or complete, complex workflows for chromatography and mass spectrometry.

When selecting an automation platform, it's crucial to look beyond your immediate needs.

Key considerations include:

  • Throughput and Scalability
    • Does the platform offer configurations that match your current and future sample load? The PAL System scales from the single-tool RSI to the high-throughput DHR with options like LC/MS Multiplexing.
  • Modularity and Flexibility
    • Can the system adapt to new applications? The PAL System's modular "Tool Box" design allows you to add new techniques like SPME, µSPE, or Dynamic Headspace as your lab's requirements evolve.
  • Instrument Compatibility
    • Will it work with your existing analytical instruments? The PAL System is designed for seamless online injection and software integration with all major GC, LC, and MS vendors.

CTC Analytics AG (Computer Technologie Cueni) is the Swiss company that has been developing and manufacturing the PAL System since 1985. "PAL System" (Prep and Load System) is the globally recognized brand name for the sample handling platform, and PAL is a registered trademark of CTC Analytics AG.

The PAL System is available in three main configurations (in various sizes) to match different laboratory needs for throughput and workflow complexity:

  • PAL RSI (Robotic Sample Injection): A robust and cost-effective solution for reliable automated injections and basic sample preparation. It is the ideal starting point for automation and can be upgraded.

  • PAL RTC (Robotic Tool Change): This model offers greater flexibility and productivity by automatically changing tools (e.g., different syringes, extraction tools). This enables complex, multi-step workflows to run unattended 24/7.

  • PAL DHR (Dual Head Robotic): The most productive model, featuring two independent robotic heads. It can perform two workflows simultaneously, doubling the throughput for high-demand applications like LC/MS multiplexing.

PAL Systems are available through a global network of certified OEM partners and value-added resellers (explore our Distribution Network). These partners often sell the PAL System as an integrated front-end solution for their analytical instruments (e.g., GC/MS, LC/MS).

To find the ideal configuration for your laboratory, we recommend using our PAL Product Finder.

For purchasing inquiries or to discuss a potential collaboration, please contact us through our website or learn more about how to become a partner.

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For volatile organic compounds (VOCs analysis), several automated sample preparation techniques can be applied depending on matrix complexity and required detection limits:

  • Headspace analysis: Ideal for routine gas-phase sampling above liquid or solid matrices.

  • Dynamic headspace: Uses continuous gas purging through an ITEX microtrap to concentrate trace-level volatiles.

  • SPME Arrow: Solvent-free sorptive extraction techniques offering superior sensitivity for trace organic pollutants in environmental samples.

Testing for Per- and Polyfluoroalkyl Substances (PFAS) in drinking water, surface water, and wastewater requires trace-level precision and strict background contamination controls. Regulated protocols like EPA 1633 or EPA 537.1 rely on Solid Phase Extraction (SPE) or Micro-SPE coupled with LC-MS/MS.

The PAL System provides dedicated hardware configurations for pfas analysis, executing extraction, cleanup (using WAX cartridges), and sample enrichment directly on the rail. To ensure accurate results at parts-per-trillion (ppt) levels, workflows designed for testing pfas in drinking water utilize fluoropolymer-free fluidics and wash stations to prevent ambient background interference and sample carryover.

The PAL System is an essential tool for high-throughput life science research.

  • For Proteomics analysis: It automates labor-intensive and error-prone steps such as protein digestion, post-digestion peptide cleanup (e.g., µSPE), and precise injection into the LC/MS, ensuring the high degree of reproducibility required for comparative studies.

  • For Metabolomics analysis: It provides robust automation of extraction procedures (e.g., Bligh & Dyer for polar and non-polar metabolites), derivatization for GC/MS analysis, and highly precise injections, which are critical for detecting subtle metabolic changes between sample groups.

The PAL System provides robust, automated workflows for the analysis of various hydrocarbon contaminants:

  • For PAH analysis: In complex matrices for environmental and food safety applications, the system automates the necessary extraction, cleanup (e.g., µSPE), and injection steps. This ensures the high recovery and reproducibility critical for reliable PAH testing at trace levels.

  • For MOSH/MOAH analysis: The determination of Mineral Oil Saturated Hydrocarbons (MOSH) and Mineral Oil Aromatic Hydrocarbons (MOAH) is a significant challenge, particularly in food analysis. The PAL System automates the complex sample preparation, including online LC-GC coupling, to effectively fractionate the two classes and remove interferences. This high level of automation provides the reproducibility needed for reliable quantification.

Yes, the PAL System excels at the automated sample preparation for FAME. It automates the entire transesterification process for Fatty Acid Methyl Esters, including the precise addition of reagents for saponification and methylation, liquid-liquid extraction, and final injection into the GC. This not only improves the reproducibility and throughput of FAME analysis but also enhances lab safety by minimizing manual handling of hazardous reagents like BF3-methanol during FAME derivatization.

The PAL System provides a complete, automated solution for trace-level PFAS analysis, addressing the critical challenge of background contamination. To ensure the lowest detection limits, a dedicated range of PFAS-free consumables (syringes, tubing, vials) is available. The system's flexibility allows it to automate a variety of extraction and cleanup techniques, including online SPE, Micro SPE (µSPE), and SPME. This versatility enables reliable and reproducible results across a wide range of matrices such as food, food contact materials, and environmental samples. The PAL System is capable of automating complex, regulated workflows like EPA 1633, making it an ideal platform for applications like testing PFAS in drinking water.

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LC/MS Multiplexing is a powerful strategy to maximize the productivity of a mass spectrometer. By connecting a single MS to two or more LC systems, the PAL System can manage staggered injections so that the MS is constantly analyzing samples instead of waiting for a column to finish its run and equilibrate. This approach can double or even triple your sample throughput without the cost of an additional mass spectrometer.

While static headspace analysis samples a fixed equilibrium volume of gas, Dynamic Headspace (DHS) is an exhaustive extraction technique that provides superior enrichment for trace-level analysis. The automated In-Tube Extraction (ITEX) process involves:

  1. Purging & Trapping: The sample is heated while an inert gas repeatedly purges the headspace. This gas flow carries the volatile compounds through a microtrap filled with a specific adsorbent material, which captures and concentrates the target analytes.

  2. Thermal Desorption: The trap is then rapidly heated, releasing the concentrated analytes as a sharp band into the GC/MS for analysis. This dynamic process allows for much lower detection limits, making it the ideal technique for demanding applications like trace VOCs analysis in environmental samples or the analysis of additives in plastics.

Solid phase microextraction (SPME) is a solvent-free technique where a fiber coated with an extraction phase is used to isolate analytes. The PAL System automates SPME in two primary modes:

  • Headspace SPME: The fiber is exposed to the vapor phase above a liquid or solid sample, making it ideal for the analysis of volatile and semi-volatile organic compounds (VOCs analysis).

  • Immersion SPME: The fiber is dipped directly into a liquid sample to extract less volatile or non-volatile analytes.

While traditional SPME fibers are effective, the newer, more robust SPME Arrow offers superior performance. Its unique design combines a much larger surface area and volume of extraction phase with a robust metal core and piercing head, resulting in higher sensitivity, faster extractions, and a significantly longer lifetime. Learn more about the PAL System's SPME capabilities.

µSPE, or Micro SPE, is a miniaturized and automated Solid Phase Extraction technique that uses Micro SPE Cartridges and operates in two primary modes for highly efficient sample preparation:

  • Pass-Through Cleanup: In this mode, the sample extract is passed through the cartridge. The sorbent is chosen to retain matrix interferences while allowing the analytes of interest to pass through for collection and analysis. This is a common approach for cleaning up complex extracts, such as in QuEChERS workflows.

  • Bind-and-Elute (Enrichment): Here, the sorbent is selected to bind and retain the target analytes while the sample matrix is washed away. The purified analytes are then eluted using a small volume of a different solvent. This mode is ideal for analyte enrichment and fractionation.

The versatility of µSPE, determined by the cartridge chemistry, enables a wide range of applications, from general cleanup to targeted analysis like PFAS analysis using weak anion exchange (WAX) cartridges, or fractionation in metabolomics analysis. Key advantages are minimized solvent use, cleaner extracts without sample dilution, and improved data quality, leading to higher instrument uptime.

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The PAL Pipette Tool LLD FT enhances standard automated liquid handling by combining air-displacement pipetting with smart sensing and mechanical tube handling:

  • Liquid Level Detection (LLD) --> Actively senses the surface height of liquids in open vials or tubes. This eliminates fixed-depth aspiration errors, prevents tip submersion contamination, and manages samples with fluctuating fill volumes or variable surface tension.

  • FlipTube (FT) Automation --> Uses mechanical pins to open and close FlipTubes, paired with a vacuum suction cup for secure tube transport to on-board modules like the Vortex Mixer (operating at up to 2000rpm).

  • Evaporation-Free Workflows --> Mechanically sealing tubes immediately after reagent dispensing creates a closed-loop environment that prevents volatile solvent evaporation during multi-step prep.

To perform an automated serial dilution on the PAL System:

  • Method Configuration --> Define the dilution factor, starting concentration, diluent volume, and mixing parameters using the PAL Method Composer or your preferred Chromatography Data System (CDS).

  • Robotic Liquid Handling --> The robotic head picks up a dedicated liquid tool, dispenses precise diluent volumes into target vials, and transfers the exact stock aliquot into the first dilution step.

  • Automated Mixing --> The vial is placed into an integrated vortexer or agitator module to achieve homogeneous mixing before transferring the aliquot to the next step.

  • Direct Injection --> Once the calibration series is prepared, the PAL System delivers the standards directly to the analytical instrument without manual handling.

A serial dilution is a stepwise, sequential dilution of a substance in solution, where the concentration decreases by a constant factor at each step. It is commonly used to construct standard calibration curves, prepare concentration series for bioassays, or bring high-concentration samples within an instrument's dynamic range.

Executing this manually is repetitive and prone to volumetric errors. Implementing automated sample preparation for serial dilutions replaces manual pipetting with high-precision robotic liquid handling. The system dispenses diluent, transfers precise aliquots from vial to vial across standard trays or microplates, and activates integrated vortex mixers between steps to guarantee thorough mixing. This yields linear calibration curves (R2 > 0.999), minimizes human error, and conserves valuable reagents.

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To prevent cross-contamination in sensitive trace applications (such as PAH Analysis or PAH testing), the PAL System utilizes active wash stations and customizable rinse protocols. Syringes and fluidic lines can be washed with multiple solvents before and after sample transfers. For demanding workflows, Robotic Tool Change (RTC) enables the system to switch between separate, dedicated liquid handling tools for different steps, maintaining complete analytical isolation.

Automation directly enhances environmental sustainability by improving process efficiency and minimizing lab waste:

  • Plastic Waste Reduction: Automated liquid handling using reusable smart syringes with automated washing stations drastically reduces disposable plastic pipette tip consumption compared to manual processing.

  • Metric Scores: In formal AGREEprep (Analytical Greenness Metric for Sample Preparation) evaluations, transitioning from manual to PAL RTC-assisted sample prep improves overall greenness scores by eliminating single-use plastic waste and lowering operator exposure hazards.

  • Right-First-Time Efficiency: Eliminating manual pipetting errors yields calibration curves (R2 > 0.9992) and repeatability (RSD < 5%), preventing costly sample re-runs, solvent waste, and unnecessary instrument energy usage.

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PAL System software options, e.g., Chronos or the PAL Method Composer, use overlapping dynamic scheduling to optimize sample timing. While the GC/MS or LC/MS instrument actively analyzes Sample A, the system prepares Sample B in parallel (e.g., executing dilution, FAME derivatization, or extraction). The next sample is ready for injection the instant the analytical run finishes, eliminating idle time during overnight operations. This effectively removes batch effects and keeps the MS running continuously. 

High-Throughput Screening (HTS) is an automated testing strategy that allows scientific laboratories to rapidly screen and evaluate thousands of chemical compounds, biological samples, or clinical assays in a short period. HTS relies heavily on robotics, automated liquid handling, and software scheduling to execute parallel processing without manual bottlenecks.

The PAL System supports high-throughput screening by integrating multi-well plate handling, Robotic Tool Change (RTC), and LC/MS Multiplexing. Multi-head configurations can perform sample preparation steps simultaneously or manage staggered injections across multiple LC/MS systems, maximizing instrument uptime during continuous 24/7 operation.

PAL SMART Consumables, such as SMART Syringes, SPME Fibers, and SPME Arrows, feature an embedded chip that stores key information (e.g., part number, volume, usage history). When used with a PAL3 Series II system, this provides:

  • Full Traceability: Automatically logs the exact consumable used for each sample, ensuring a complete and auditable history.

  • Error-Free Operation: The system automatically recognizes the tool and its parameters, preventing mistakes.

  • Optimized Uptime: Tracks the usage of each consumable and alerts the user when it's time for replacement, preventing unexpected failures during a run. This "Smart" technology enhances process safety, increases result confidence, and lowers the overall cost of ownership.

The PAL System is designed for seamless integration and is controlled directly from all major Chromatography Data Systems (CDS) from vendors like Agilent, Bruker, SCIEX, Shimadzu, Thermo Fisher Scientific, and Waters. This allows for a single point of control for the entire analytical workflow.

To facilitate the creation of custom automation methods within these CDS environments, we offer the PAL Method Composer. This intuitive, graphical tool allows users to build complex workflows simply by dragging and dropping individual steps, without the need for programming.

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