Sample Preparation for Chromatography: How Much Can Be Automated?

May 02, 2014

Modern autosamplers and workstations possess a range of capabilities, in addition to simple liquid handling, that allow automation of sample preparation steps traditionally performed manually. Scientists in many laboratories are considering automating labour-intensive sample processing steps — such as weighing, filtration, dilution, solid-phase extraction, evaporation, and reconstitution. Most quantitative methods require preparation of calibration standards that can be as time-consuming as preparing the samples. This article reviews the automation capabilities available and some practical considerations to take into account when choosing to automate some or all of the sample preparation and handling steps that must be done before analysis.



Those of us who experienced the early days of high performance liquid chromatography (HPLC) may remember manual injections and strip-chart recorders on chromatographic instruments. In the mid-1980s rapid development of autosamplers, integrators, and personal computers (data systems) greatly simplified sample preparation and contributed to the development of modern automated chromatographic instrumentation.

Fifteen years later, in 1995, an article published in LCGC North America (1) provided insights from experts regarding sample preparation for chemical analysis, and predictions regarding where developments would head over the next decade. Increasing sample loads, the need for higher productivity in the face of decreasing analyst skill levels, and increasing issues with worker safety, regulatory constraints, and information management were all listed. Sound familiar?

Noteworthy were consensus opinions on the need for rugged and reliable automation systems that could be automated. It was agreed that future trends would include sample miniaturization and reduced solvent usage. Also, experts agreed that pressure from industry programmes and government agencies could play a significant role in stimulating development. Another major theme was the need for better, more universal communication between instruments to allow automation devices to communicate with any vendor's chromatography platforms.

Opinions differed regarding the importance of integrated (serial) sample processing versus batch processing, and the need for flexible (user-defined) robotic systems that provide a set of "tools" that could be customized versus specific systems designed to provide automated defined solutions. It was stated that developments in detection technology, particularly in the area of liquid chromatography–mass spectrometry (LC–MS), might reduce the need for extensive sample preparation.

A later article (1998) (2) on sample preparation for LC–MS–MS emphasized automation of three common procedures — dilute-and-shoot, solid-phase extraction (SPE), and liquid–liquid extraction — as well as post-injection techniques — column switching and on-line SPE— to manage the sample matrix. The authors also recognized the emerging need for "massively parallel" sample preparation and analysis driven by modern drug discovery practices such as combinatorial chemistry.

This review addresses the following questions: What driving forces are stimulating the continued development of the automation of sample preparation for gas chromatography (GC) and HPLC today? Where do we stand regarding current automation capabilities? What are the next developments on the horizon?

Defining Sample Preparation

One of the most formidable challenges to standardization and automation in the analytical laboratory is the broad range of sample types. Samples can be gaseous, liquid, solid, or a mix of phases (for example, biological tissues). Some sample types lend themselves to relatively straightforward collection of homogeneous samples — for example water, some liquids, and air samples. Other solid sample types, such as whole fruits and vegetables or production batches of pharmaceuticals, require physical homogenation of larger representative samples before reducing the sample size to a more easily manipulated volume. This article will address only the automation of processing steps for small, homogeneous, or homogenized samples.

Samples are often intact prior to sample preparation, but there are a few examples of sample collection devices that perform partial sample preparation as part of the process of collecting the sample. Air sampling onto adsorbent tubes concentrates analytes and simplifies transport. Similarly, solid-phase microextraction (SPME) (3) and stir-bar sorptive extraction (SBSE) (4) concentrate analytes onto extraction phases on fibres or stir bars, respectively, that can stabilize the analytes and facilitate transport. Although typically performed manually, these methods simplify downstream sampling and analysis, and can be automated with relative ease.