Cambridge’s main protein-analysis instrument is 11 years old, slower and less sensitive than modern alternatives, and must be replaced to keep up with demand. The Cambridge Centre for Proteomics processes thousands of samples each year for biologists across the university, as well as for pharmaceutical companies and international research groups. Its workhorse mass spectrometer—a Thermo Fisher QExactive—can no longer identify and measure proteins quickly enough to avoid growing backlogs. The centre plans to install a Thermo Fisher Orbitrap Exploris 480, which scans faster and detects proteins in smaller samples, such as a few thousand cells or tiny volumes of blood or tissue fluid. If the upgrade succeeds, researchers will be able to run more experiments in less time, and the facility expects to lower access charges. The instrument will also support studies that require precise measurement of absolute protein quantities, which is important for understanding how cells function in health and disease. This is primarily an infrastructure investment: it does not test a specific hypothesis, but it will enable a wide range of fundamental and applied biological research across the BBSRC’s priority areas.
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Context The Cambridge Centre for Proteomics (CCP) is a highly regarded proteomics facility at the University of Cambridge. The CCP facility has grown steadily over 24 years in both user access and research capabilities. Currently it provides core mass spectrometry and proteomics services for multiple departments across the university, including those within the Schools of the Biological Sciences, Clinical Medicine, and Technology. The centre's services extend beyond local academic boundaries, offering experienced proteomics support and expertise to pharmaceutical companies, small and medium-sized enterprises, and additional national and international research groups in a broad range of scientific research. The facility runs alongside the proteomics technology development research group, led by Kathryn Lilley. Interactions with this group ensures the facility can access and build expertise in cutting-edge technology and advanced informatics pipelines, making sophisticated proteomics capabilities available to a broad research community. Despite processing thousands of samples annually, CCP operates with only three mass spectrometry instruments: a Thermo Fisher Fusion Lumos, a Bruker timsTof HT, and an aging Thermo Fisher QExactive mass spectrometer. The QExactive, which has been the facility's primary instrument for 11 years, is now notably less sensitive and slower compared to newer models. This application outlines the critical replacement of this instrument with the Thermo Fisher Orbitrap Exploris 480 (OE480) which will sustain high-quality services for CCP’s existing and expanding user base well into the future. Objectives Our first objective is to purchase and install the OE480 mass spectrometer to increase our capacity and meet growing demand. We aim to enhance mass spectrometry capabilities by accessing a faster instrument and leveraging advanced multiplexing techniques, such as 35-plex TMT. The OE480 will significantly improve our research efficiency, enabling the identification and quantification of a greater number of peptides and proteins in a shorter time. Compared to our current QExactive, the OE480 offers superior sensitivity and speed. With extensive experience in mass spectrometer installations—having successfully implemented numerous instruments over the years—we are well-prepared for this upgrade. Post-installation, our second objective will be to conduct comprehensive user training through on-site sessions and targeted courses for students and staff, validating the instrument using standard protocols, and revising and maintaining our cost recovery model. Over 15 years, CCP has recovered all facility costs through recharging fees, and the OE480 will further support this financial sustainability while enabling continued expansion to meet evolving research demands. Potential application and benefits The OE480 offers high sensitivity and fast data acquisition, enabling more comprehensive protein coverage from complex samples. The instrument's advanced capabilities will expand the range of proteomics experiments, particularly those with limited sample quantities. Studies will thus be enabled where only low cell numbers, smaller tissue amounts or reduced volumes of biofluids are available. Furthermore, efficient experimental designs combining multiple samples per experiment will increase experimental throughput. Moreover, the OE480 is particularly well-suited for experiments requiring precise measurement of absolute protein and peptide quantities. Its increased scan speed when compared to our current instrument will reduce overall run times, thereby improving facility capacity and minimising user queues. A new pricing policy will leverage this increased capacity to reduce access charges. Its capabilities will not only support the specific research needs of co-investigators but will benefit researchers working within the BBSRC's research framework.
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