Maximizing the Potential from Blood Samples Through Automated Phase Separation

Maximizing the potential from blood samples through automated phase separation
Tecan's Phase Separator™
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Author: Alexandra Sommer, Senior Product Manager, Clinical Diagnostics at Tecan

Blood is a powerful clinical resource for evaluating an individual’s overall health, providing a wealth of valuable data that can be collected through a relatively straightforward and painless process. Information from blood samples can be used for the diagnosis and monitoring of a range of health issues – including organ failure, diabetes, high cholesterol, vitamin deficiencies, infections and even cancers – and is also critical for the progression of clinical research.1-3 Excess blood from samples collected from clinical applications is a useful source of material for current and future research, and can be stored in a biobank until needed. This article explores the value that lies within blood, and how automation can improve its handling to maximize access to this data.

The diagnostic and research power of the elements found in blood

Following collection, blood is typically separated into three primary components – plasma, buffy coat and erythrocytes – to isolate specific constituents for use in downstream research and clinical protocols. While all three components are valued by laboratories worldwide, the plasma and buffy coat layers are at the core of cutting-edge research for various clinical indications.

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Liquid biopsies

Conventional tissue biopsies are the established standard for the diagnosis and confirmation of many cancers, but they come with several limitations, including the invasiveness and risk to patients of surgical collection procedures, and the need to fix the sample following collection. Sample fixing uses chemicals that may impact the interpretation of samples, potentially delaying reporting of results. Liquid biopsy offers an alternative source of diagnostic data that is less invasive and more convenient to collect. The specimens can be used to study circulating tumor cells or cell-free DNA (cfDNA) to analyze mutations, methylation patterns or post-translational modifications to give an overall picture of the cancer, as well as to monitor patients during and after treatment. Such analyses offer a more comprehensive assessment of tumor heterogeneity, with the potential to serve as both diagnostic and prognostic markers.6

At the moment, liquid and tissue biopsies function as two distinct tests, with tissue biopsies being the gold standard for all cancer-related testing, while liquid biopsies are often used as a complementary test. Liquid biopsies can best be used to estimate the risk for metastatic relapse or metastatic progression, and allow the stratification and real-time monitoring of therapies, as sampling can be easily repeated as often as necessary to monitor the patient’s progress. While test sensitivity challenges still exist, and more support for clinical utility is needed, liquid biopsies have a high potential to make a difference in patient care, enabling early diagnosis, guiding clinical decisions by predicting response to therapies, monitoring markers for minimal residual disease in curative settings, and transforming companion diagnostics. Further validation of cfDNA monitoring in oncology applications – for example, to assess test accuracy and the ability to identify various cancer types – is necessary before it gains widespread acceptance in clinical practice,7 with advancements in automation and high throughput screening being pivotal to allow researchers to accurately analyze cancer biomarkers in large patient cohorts.

Biobanking for research studies

Blood sent to biobanks is separated into its component parts before long-term storage. The buffy coat in particular – despite comprising less than one percent of total blood volume – holds significant importance for medical research and diagnostics, due to its high concentration of white blood cells and platelets. Buffy coat microRNA, for example, has been studied for potential biomarkers for the prediction and diagnosis of different cancer types. Researchers also often prefer to extract genomic DNA from the buffy coat rather than from whole blood, since it can yield large quantities from just a small sample. This is critical to ensure an ample supply of genetic material for genome-wide association studies, and for future genomics and proteomics research across various disease areas, including oncology, neurodegenerative diseases and metabolic disorders.

Challenges in blood sample separation

Traditionally, the separation of blood into its primary components has been a slow and labor-intensive manual process, and has been susceptible to human error and technician-specific variability. This issue is compounded by the fact that laboratories in hospitals and biobanks are under pressure to deal with large numbers of samples, and to ensure careful separation to prevent contamination between the different blood components. Blood is typically separated by centrifugation to form three distinct layers. The buffy coat makes up less than one percent of the blood, and appears as a thin layer between the plasma and erythrocytes. This makes its isolation – typically carried out manually with a Pasteur pipette – hard to standardize, leading to inconsistent recovery rates. Even when automation is available, the detection of liquid-liquid interfaces after centrifugation can be problematic as barcode labels on collection tubes may interfere with optical sensors. This, in turn, slows down processing times, particularly if labels need to be removed, which can also lead to potential loss of the chain of custody.

Streamlined phase separation

Tecan has introduced an innovative solution – Phase Separator™ – in response to the challenges posed by whole blood separation. This cutting-edge technology not only saves time, but also enhances accuracy within laboratory workflows. The Phase Separator is integrated into the Air Flexible Channel Arm™ (Air FCA) of the Fluent® Automation Workstation, and uses a unique pressure-based approach to liquid-liquid separation. Because it effectively addresses the critical challenge of detecting liquid-liquid interfaces and separating adjacent phases with minimal contamination, the Phase Separator is particularly well-suited for extracting plasma or buffy coat layers from centrifuged whole blood samples. Whether working with tubes or plates, it offers increased operational efficiency thanks to a combined phase detection and pipetting action.

The Phase Separator operates at remarkable speeds and can aspirate plasma from 24 tubes of centrifuged blood in under 10 minutes,* and this speed is doubled on dual-arm systems. Because it is integrated into an existing workstation, the technology requires no additional bench space or equipment maintenance. Additionally, it accurately detects liquid levels from within the tube or plate, eliminating interference from barcodes or other markings and further contributing to its precision in laboratory applications and biobanking.

Summary

Blood provides valuable insights into various health issues for both clinical and research applications, but the separation of blood components has traditionally been a slow and manual process, posing challenges for laboratories amid increasing demand. Tecan’s Phase Separator – using a unique pressure-based phase boundary detection technology – combines efficient identification of liquid-liquid interfaces with precise and rapid liquid separation, with minimal risk of contamination. This technology improves the efficiency and accuracy of blood processing workflows within biobanks and clinical labs, helping to speed up research and diagnostics.

For further information about Tecan’s Phase Separator, please visit www.tecan.com/phase-separator.

*Timing is volume dependent. Time given for separation volumes of 5 ml.

The Fluent Phase Separator is an open liquid handling platform. No performance claims are made by Tecan. Performance validation is required by the customer.

References

  1. Casanova-Salas I, et al. Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer. Eur Urol. 2021;79(6):762. doi:10.1016/J.EURURO.2020.12.037
  2. Park S, et al. Blood Test for Breast Cancer Screening through the Detection of Tumor-Associated Circulating Transcripts. Int J Mol Sci. 2022;23(16). doi:10.3390/IJMS23169140/S1
  3. Sohn E. Diagnosis: Frontiers in blood testing. Nature. 2017;549(7673):S16-S18. doi:10.1038/549s16a
  4. Abeje G, et al. Comparison of capillary, venous and buffy coat blood samples in detecting Plasmodium species among malaria suspected patients attending at Hamusite health center. A cross-sectional study. BMC Infect Dis. 2021;21(1). doi:10.1186/S12879-021-06290-6
  5. Chagas CRF, et al. The buffy coat method: A tool for detection of blood parasites without staining procedures. Parasit Vectors. 2020;13(1):1-12. doi:10.1186/S13071-020-3984-8/FIGURES/3
  6. Volckmar AL, et al. A field guide for cancer diagnostics using cell-free DNA: From principles to practice and clinical applications. Genes Chromosomes Cancer. 2018;57(3):123-139. doi:10.1002/GCC.22517
  7. Stawski R, et al. Current trends in cell-free DNA applications. Scoping review of clinical trials. Biology (Basel). 2021;10(9). doi:10.3390/BIOLOGY10090906/S1