Transforming molecular diagnostics workflows
Professor Jordi Vila, Head of Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Spain, describes how a new, fully automated molecular diagnostic system, has the potential to improve productivity and turnaround times at his busy organ transplant reference laboratory in Barcelona, Spain.
The Hospital Clinic of Barcelona serves a local population of 540,000, in addition to being a National and International Centre of reference, providing the full range of medical and surgical specialties. The Hospital’s Department of Clinical Microbiology is also a reference laboratory for organ transplantation.
Operating 24 hours a day, seven days a week, the laboratory has experienced a growing workload in recent years, mainly associated with an increase in molecular biology assays, including viral loads for Human Immunodeficiency Virus type 1 (HIV-1), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) and Cytomegalovirus (CMV). In particular, the laboratory has observed an increase in HCV viral load requests, related to new treatment regimens, as well as an increase in CMV viral load requests for organ transplant patients.
The total number of viral load assays performed annually in the Barcelona laboratory for HIV-1, HCV, HBV and CMV are shown in figure 1.
The need for workflow improvements
Like many laboratories throughout Europe, the Virology Section at the Hospital Clinic of Barcelona must cope with this growing workload without any increase in staffing levels. As a result, there is a strong interest in workflow improvements as a means to increase productivity within the laboratory and to ensure the quality of generated results.
Speed and efficiency are particularly important when clinical decisions are dependent on the result, and an increase in automation, particularly in the disciplines of serology, molecular diagnostics and bacteriology, have played an important role in achieving greater speed and efficiency in the Clinical Microbiology Laboratory.
The aims of the laboratory’s investigations into increased automation and workflow improvements were to reduce turnaround times, to reduce waste (of time and reagents), to maximise the use of staff, space and equipment, to increase productivity and to reduce opportunities for error.
Limitations of current methods
When looking at potential areas for improvement, a number of drawbacks were observed in the current methods used for obtaining HIV-1, HCV, HBV and CMV viral loads. These methods require separate platforms for nucleic acid extraction, amplification and detection. Numerous steps are required to achieve the final result, which are quite labour intensive. In order to be cost effective, assays are performed in batches (table 1), which limits the number of assay runs performed in a week. This has a major impact on result turnaround times and has significant cost implications for urgent samples.
In addition to these limitations, all of the existing equipment and sample preparation is located in a small room where space is of a premium. As a result, working conditions are very crowded and some tasks, for example reagent preparation, need to be performed in an adjacent room, which is not ideal.
A new, fully automated system
An independent time/workflow analysis study was performed at the Hospital Clinic of Barcelona Virology Laboratory by Nexus Global Solutions (Plano, Texas, USA). This study compared workflows and time to results between current viral load methods and the new, fully automated DxN VERIS Molecular Diagnostics System (Beckman Coulter Inc.).
Launched at ECCMID 2015, the DxN VERIS Molecular Diagnostics System consolidates DNA extraction, amplification and detection on a single automated instrument. By reducing manual intervention and automating the process from sample loading to reporting of results, this system has the potential to transform virology laboratory workflows.
DxN VERIS assays are supplied in a unique, single cartridge system and all consumables and reagents are stored on-board the system, which reduces preparation time and effort. Unlike traditional plate-based systems, there is no need to batch assay runs and there are no empty wells, which reduces wastage and consumable costs. With true single sample random access, the DxN VERIS platform allows viral load assays to be performed as soon as they arrive in the laboratory and the short assay runtimes ensure rapid turnaround times.
Comparative performance studies at several DxN VERIS evaluation sites[1-13] have shown that the VERIS HBV, HCV, HIV-1 and CMV assays demonstrate comparable precision, sensitivity and linearity to a range of alternative, commercially available viral load methods.
Workflow study results
It was decided to run DxN VERIS samples as single sample random access, as intended by the manufacturers. This meant that samples could be loaded straight on to the DxN VERIS when they arrived in the laboratory, which is much faster than daily batch testing. The results of the comparative workflow study at the Hospital Clinic of Barcelona are shown in table 2 and figures 2 and 3.
In particular, the DxN VERIS workflow involved far fewer steps, especially pre-analytical steps, reduced hands-on time and fewer consumables. The time to the first result is greatly reduced compared to current methods and, notably, subsequent results are available every 2.5 minutes. For the current methods, results are not available until the end of the run.
During a normal working week, the DxN VERIS system allowed much faster turnaround of results, with all results being reported in under 24 hours (figure 3).
Workflow improvements
The DxN VERIS Molecular Diagnostics System offers some important workflow advantages compared to current methods for the determination of viral loads for HIV-1, HCV, HBV and CMV. For example, the DxN VERIS system allows continuous loading of samples, which eliminates the need for batching and, with true, single sample random access, it allows urgent samples to be added at any time. This is a particularly important aspect for us as a reference centre where urgent test requests can arrive at the laboratory at any time of day. The DxN VERIS system allows laboratories to perform assays for several viruses at the same time, on the same platform, which allows flexibility, and with adaptable racks, it also has the versatility to accept a variety of sample tube types.
As a fully automated system, the DxN VERIS system decreases the potential for human error and reduces turnaround times considerably compared to the current methods, which allows much faster reporting of results to service users. Unlike current methods, technicians are not required to pipette samples and reagents, which is an important ergonomic advantage. By reducing manual time requirements it will allow laboratories to achieve the most from existing staffing levels, helping to maximize productivity within the laboratory.
In addition to this, consolidation of extraction, amplification and detection for these four targets onto a single platform is an important consideration for laboratories, like this, where space is very limited.
The implementation of automated methodologies, such as this, has the potential to improve the quality and delivery of virology services and, for patients, it allows infectious disease results to be obtained at the earliest opportunity with high sensitivity and specificity.
For further information about the DxN VERIS Molecular Diagnostics System and the DxN VERIS assays currently available, please contact: Tiffany Page, Senior Pan European Marketing Manager Molecular Diagnostics, Email: info@beckmanmolecular.com or visit www.beckmancoulter.com/moleculardiagnostics.
References
1. Williams, JA, Rodriguez, J, Wang, Z et al (2014) Poster presentation, ESCV, Prague.
2. Drago, M, Franchetti, E, Fanti, D and Gesu, GP (2015) Poster presentation, EuroMedLab, Paris.
3. Zurita, S, Gutiérrez, F, Folgueira, MD et al (2015) Poster presentation, EuroMedLab, Paris.
4. Christenson, R, Maggert, K, Ruiz, RM et al (2015) Poster presentation, ECCMID, Copenhagen.
5. Trimoulet, P, Tauzin, B, Belloc, E et al (2015) Poster presentation, EuroMedLab, Paris.
6. Gilfillan, R, Wang, Z, Xu, Y et al (2014) Poster presentation, ECCMID, Barcelona.
7. Xu, Y, Gilfillan, R, Wang, Z et al (2014) Poster presentation, ESCV, Prague.
8. Mengelle, C, Sauné, K, Haslé, C et al (2014) Poster presentation, RICAI.
9. Mengelle, C, Sauné, K, Haslé, C et al (2015) Poster presentation, ECCMID, Copenhagen.
10. Silvestro, A, Duan, H, Lim, S et al (2014) Poster presentation, ECCMID, Barcelona.
11. Li, Q, Williams, J, Maggert, K et al (2014) Poster presentation, ECCMID, Barcelona.
12. Xu, Y, Dineen, S, Annese, V et al (2014) Poster presentation, ESCV, Prague.
13. Williams, JA, Rodriguez, J, Wang, Z et al (2014) Poster presentation, ECCMID, Barcelona.
