Over 176,000 new cases of multiple myeloma (MM) are reported globally each year according to the International Myeloma Foundation1, and recent treatment advances have made the disease undetectable using conventional techniques in many patients. Unfortunately, MM remains incurable, and differences in disease progression persist among patients with no measurable biomarkers. This highlights the need for new technologies capable of identifying residual disease that may account for differences in patient outcomes. UK-based specialist diagnostics company Binding Site – part of Thermo Fisher Scientific – has developed a new IVDR-certified* solution, the EXENT® System**, to transform the diagnosis and assessment of patients with monoclonal gammopathies.
Addressing the unmet needs in monoclonal gammopathy assessment
Conventional methods used to diagnose monoclonal gammopathies and assess patient response to treatment involve measuring the monoclonal proteins (M-proteins) through serum protein electrophoresis or immunofixation electrophoresis. Dr Stephen Harding, Vice President of R&D at Binding Site, explained: “MM patients usually present with a high disease burden, with somewhere in the region of 109 malignant cells in their bone marrow. Electrophoresis gels are sensitive to a concentration of around 107.5, and so this technique can accurately identify these patients on initial presentation. The problem arises after therapy, where there are far fewer malignant cells remaining, and electrophoresis gels struggle to accurately quantify the low cell numbers. This makes it challenging to quantify treatment success and identify relapses early on. Furthermore, therapeutic monoclonal antibodies (tmAbs) can be wrongly identified as endogenous monoclonal proteins and may be interpreted as residual disease, skewing electrophoresis results.”
The EXENT System is a fully integrated and automated MALDI-TOF mass spectrometry system that enables M-protein identification and measurement in serum with higher sensitivity than conventional methods. It addresses the unmet clinical need for more sensitive blood-based analytical methods to differentiate between patient subsets, helping to inform the timing of bone marrow biopsies looking for residual disease2. This empowers clinicians to effectively diagnose and monitor patients with monoclonal gammopathies, including multiple myeloma, throughout their treatment journey.
The choice of partner was the key to success
Sample preparation for this application is extremely intricate, involving the extraction of immunoglobulins from samples at high volumes, then spotting onto MALDI plates at low volumes. Samples are pipetted from primary tubes and incubated with beads, washed to clear all the serum proteins, and spotted onto the array, which often involves the transfer of liquids down to a single microliter. Binding Site understood that it needed to establish an automated workflow to ensure consistency and precision in sample preparation. It approached various vendors with these specific requirements, and ultimately chose Tecan’s OEM development and manufacturing service, thanks to the company’s renowned experience with laboratory automation.
The two companies worked together to develop the EXENT-iP®500 automated sample preparation instrument as the first of three integrated modules. Dr Harding described this exciting process: “We chose the Fluent® 780 Automation Workstation and worked closely with Tecan from the beginning to refine and improve our workflow. For example, we needed greater accuracy in some of the pipetting steps – the spotting especially – and a stronger magnet to pull down the beads, as we wanted to wash the samples vigorously. The Tecan team understood our goals exactly, and they were always able to come up with a tailored approach to meet our needs, enabling us to achieve the desired precision and throughput.”
Improving workflow efficiency and analytical accuracy
The Fluent 780 platform, combined with Tecan’s engineering expertise, has streamlined the entire workflow to include just two manual steps – loading the primary tubes, and transferring the MALDI plates to the mass spectrometer – making it an incredibly efficient process. Following sample preparation, mass spectrometry can be used to deliver extremely accurate results, offering a higher level of sensitivity than conventional methods used in the assessment of monoclonal gammopathy. Mass spectrometry offers two-dimensional separation, allowing the visualization of novel features of M-proteins that may correlate to different disease pathologies. This could potentially help to guide healthcare professionals on the best choice of therapeutic intervention.
Dr Harding concluded: “The Fluent is such a fantastic workhorse, and it really decreases the required hands-on time for staff. The technology itself is easy to use, and we’re continuously working on intelligent software to remove the subjectivity of analyzing results, making our approach even more accurate and predictable compared to manually reading electrophoresis gels. This will prove increasingly important as more tmAbs are developed and routinely used, further contaminating the spectra and complicating analysis. Without Tecan’s support, we truly believe we wouldn’t have been able to launch this product across several European countries so quickly, giving us the confidence to continue the collaboration.”
To find out more about Tecan Synergence OEM systems engineering services, visit partnering.tecan.com/synergence
For more information about Binding Site, visit www.thermofisher.com/bindingsite
