Sample Handling

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Creating consistent and task-dependent methods grows increasingly important

As clinicians, scientists and technologists deal with an extensive variety of samples for more types of analysis, the handling process takes on an increasingly important role. When sample handling is imprecise, inconsistent or both, the validity of results can be called into question. In some cases, lives might depend on those results, so the significance of using the right sample-handling tools and techniques can’t be overstated.

Maintaining sample integrity is vital; however, it can pose challenges. Robert Lund, product manager at Beckman Coulter Life Sciences (Indianapolis, Ind.), calls “proper collection and handling techniques, and storage conditions” some of the most troublesome challenges. Others include processing diverse configurations of sample sources and labware, as well as compensating for variations in the consistency of sample matrices.

Another significant challenge involves developing a customized sample-handling protocol—including sample, source and method of analysis—for a specific application. For many applications, it’s clear that more attention should be focused on sample handling. In Faraday Discussions, scientists reported using vibrational spectroscopy of biofluids as a clinical diagnostic.1 Despite the apparent promise of this technique, the authors wrote that studies “show that there is a lack of a standardized protocol in sample handling and preparation prior to spectroscopic analysis.” This is only one example of many that suggest the need for improved sample handling.

Sample systems

Regardless of the type of research and analysis, automated sample-handling systems can address many issues. “Beckman Coulter’s Biomek Automated Workstations are open-platform, liquid-handling instruments,” says Lund, “which can be configured to enable automation of multiple sample-manipulation processes, including heating and cooling, shaking and centrifugation.” These workstations can help improve efficiency while minimizing the possibility of human error in sample handling for many applications, including genomics, cellular biology and protein-sample preparation.

In all applications, repeatable and reliable results matter. “Automating sample preparation is key to improving reliability,” Lund says, because it eliminates user-to-user variability and errors for downstream detection technologies.

“The generation of greater amounts of data in research has driven the need for better ways to ensure its accuracy and integrity,” explains Lund. An automated workstation’s software is a crucial component in this quest. Other add-on software can further expand a system’s capabilities. For example, Lund notes that SAMI Process Management software schedules and executes “method steps in automated systems with multiple interventions over extended incubation times.” Researchers can also keep track of the steps in sample preparation with Beckman Coulter’s DART 2.0 data acquisition and reporting software.

 A transfer fork (gold, left) places a sample in a PHI VersaProbe II XPS system (Physical Electronics, A Division of ULVAC-PHI, Chanhassen, Minn.) for X-ray photoelectron spectroscopy, which analyzes a sample’s surface. (Image courtesy of Min Li.)

One of the most data-intensive applications is next-generation sequencing (NGS). In June 2016, Hamilton Bonaduz AG (Switzerland) and the Human Genomics Research Group (HGRG) at the University of Basel (Switzerland) teamed up to improve automated sample preparation for NGS. Mario Arangio, director of product management and partnering at Hamilton, says this collaboration “is sending out a clear sign of the recognition of the importance of NGS not only in the scientific world, but also in clinical and forensic research.”

This collaboration will involve products from even more companies. “In addition to the ongoing application developments from Hamilton Robotics Reno, the Basel lab will focus on the development and verification of methods for the most common kits,” Arangio says. These will include NGS kits from Illumina (San Diego, Calif.), New England Biolabs (Ipswich, Mass.), Pacific Biosciences (Menlo Park, Calif.) and Thermo Fisher Scientific (Waltham, Mass.). “The cooperation with the HGRG gives quick access to sequencing instruments and data analysis for verification and optimization of the methods in development,” Arangio says.

Banking biosamples

Biobanks collect human biological samples from healthcare facilities, and the samples can be used for research or clinical applications. In 2008, two Swedish entities—the Uppsala County Council and Uppsala University— collaborated to create the Uppsala Biobank. To maintain consistent handling, the Uppsala Biobank keeps its samples in a robotic freezer that is connected to a LIMS. The LIMS tracks many features of every sample, including time from collection to storage.

Researchers can order biobank samples through the medical chart system, and an advanced automatic preanalytic/multidisciplinary workflow handles them. “In this workflow, we have one aliquoting robot which can measure the volume of the sample and aliquot it in up to eight aliquots per sample in 2-D-barcoded tubes in a 1-D-barcoded SBS [Society of Biomolecular Screening] plate,” says Karolin Bergenstråhle, biobank application specialist at Uppsala Biobank. “Today, around 60 different clinics are ordering samples in approximately 30 different research projects.”

 Effective sample handling starts with acquisition, especially in human blood samples, which can be collected with less stress with advanced equipment down to the needle. (Image courtesy of BD.)

Most facilities will not have the same capabilities as the Uppsala Biobank, and they need less sophisticated but equally effective methods of sample handling and tracking. So Bergenstråhle and her colleagues “are developing a web application, which is set up to create a report file in the same manner as the robotic software.” She notes, “Smaller hospitals and clinics, which do not have the high workflow or the funding to purchase an aliquoting robot, will, with this web application, have the opportunity to collect biobank samples in the same manner, but with a manual routine.” With this approach, she says, “all you need in equipment is a 2-D–full rack barcode scanner, racks for the tubes, this web application and XML transfer from your hospital IT system.”

The Uppsala Biobank was designed for hospital use, which can create some challenges for researchers. “When being a fully hospital-integrated biobank, you have no specific personnel or infrastructure for research biobanking,” Bergenstråhle explains. “This means that you have to rely on already established infrastructures, such as sampling and sample handling by the hospital staff and clinical laboratories.” Thus a researcher must accept the sample-handling protocols used by the biobank, and these cannot be changed. “This means that we can’t help projects that have very specific demands, such as studies for metabolomics research,” Bergenstråhle says.

Safeguarding a surface

As methods of analysis become more sophisticated, sample handling grows increasingly crucial. This is especially true with X-ray photoelectron spectroscopy (XPS), which analyzes the elements on a sample’s surface and how they bond. Scientists can use XPS on a variety of sample types, ranging from crystals to soft materials, including organic films and polymers.

“The key factor is to take care of sample surfaces for contamination when preparing samples, since XPS is a surface technique that detects photoelectron signals from a region between 5 and 10 nanometers below the surface,” says Min Li, director of the materials characterization core at Yale West Campus (West Haven, Conn.). “The second key factor is that the samples need to be vacuum compatible, which means very low vapor pressure under a typical 7 to 8 pascals of pressure in the analysis chamber.”

Other constraints also impact the results from XPS. With particle samples, scientists should keep loose samples from getting in the vacuum, which will damage the pumping system. Also, Li points out that a smooth sample surface reduces background noise.

If samples aren’t handled properly, the XPS outcome will show it. As Li explains, “Surface contamination caused by sample handling will generate confusing data and meanwhile reduce the real signal intensity due to short photoelectron signal detection depth in the samples.”

Better blood sampling

Blood may be the most-handled medical sample, so companies keep devising new ways to handle it from the start. In February 2016, BD (Becton, Dickinson and Company), a global medical technology company headquartered in Franklin Lakes, N.J., received clearance from the U.S. Food and Drug Administration for the BD Vacutainer UltraTouch Push Button Blood Collection Set. According to Jeff Ezell, senior product manager at BD, this set “uses proprietary needle technology to help enhance the patient experience during blood collection.”

The technology includes a patented PentaPoint Comfort 5-bevel needle and a RightGauge ultrathin-wall cannula that enables clinicians to select a smaller-gauge needle without sacrificing sample quality and blood flow. This device has been shown to reduce penetration forces by up to 32% when compared to another leading blood collection set.

From X-rays to blood draws, researchers and clinicians need a variety of ways to handle samples, from the time they are collected through storage and analysis.

Reference

  1. Lovergne, L.; Bouzy, P. et al. Biofluid infrared spectro-diagnostics: pre-analytical considerations for clinical applications. Faraday Discussions 2016; doi: 10.1039/C5FD00184F.

Mike May is a freelance writer and editor living in Florida. He can be reached at [email protected].