As with many other cancers, the early diagnosis of brain cancer can greatly improve patient outcomes by enabling safer surgeries and timely treatments. Unfortunately, at present, brain cancer diagnosis is often challenging due to patients presenting with non-specific symptoms, including headaches or memory changes, that can contribute to a delay in tumor detection. Now, a pioneering spectroscopic liquid biopsy approach, developed by University of Strathclyde spinout company Dxcover, has the potential to change this.
In this article, we speak with Mark Hegarty, CEO of Dxcover, to learn more about how this novel test, which couples infrared spectroscopy with machine learning, can be used to rapidly detect early signs of cancer in the blood. Hegarty also reveals how a collaboration with Specac proved critical to advancing the clinical translation of this technology and shares his hopes for its impact on the future of cancer diagnostics.
Minimally invasive liquid biopsy analysis is emerging as a powerful new tool for the detection and diagnosis of cancer. However, as most liquid biopsies target specific genetic material, such as circulating tumor DNA, this approach can be limited for early-stage tumors. This is due to a low abundance of cancerous genetic material, which for early-stage brain tumors is further diminished by the blood-brain barrier.
To address this, researchers at Dxcover have developed an alternative approach that uses attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy combined with machine learning algorithms to analyze the whole molecular composition of a blood sample. The first of its kind, the Dxcover® Brain Cancer Liquid Biopsy test originates from the academic research of Dr. Matthew J. Baker, a world leader in clinical spectroscopy and co-founder and Chief Technical Officer at Dxcover. “As part of his university research, Dr. Baker worked with clinicians to prove the ability of infrared spectroscopy to detect brain cancer by analyzing blood serum,” Hegarty explains. “This resulted in a patent and led to the formation of the spinout company, ClinSpec Dx, which is now called Dxcover Limited.”
Specac has been an enthusiastic and highly motivated partner and we are very pleased with the function and improved aesthetics of the final ATR-Indexer, the Dxcover Autosampler
CEO of Dxcover
Using the Dxcover platform, a patient blood sample is dropped onto the wells of a silicon slide and dried prior to analysis. The sample is then introduced to the Dxcover® Autosampler, an ATR accessory that plugs into an FTIR spectrometer and indexes each sample well across the beam, enabling a spectrometer to record the infrared spectrum of the sample. Finally, the spectral data is analyzed by a diagnostic algorithm that has been trained using machine learning methods to detect the signals of cancer.
While routine ATR-FTIR spectroscopy has been available for decades, Dxcover has pioneered its translation to clinical use by developing its Drop.Dry.Detect.™ technique and patented hardware designed specifically for the analysis of biofluids. “Previously, infrared spectroscopy was not suited to clinical testing, as analysis relied upon a single and expensive crystal (typically diamond) which had to be thoroughly cleaned between samples, significantly limiting sample throughput,” explains Hegarty.
Crucial to overcoming this limitation was the development of the Dxcover Autosampler, during which the team leveraged expertise and instrumentation from leading ATR-accessory provider Specac. “In the initial development of the Dxcover platform, we worked independently of any supplier and developed prototype Auto-Indexer ATR units in-house, filed our patents, and began our clinical studies,” explains Hegarty. “Our favoured prototype used the Specac Quest ATR as the base optical unit because it was user friendly and highly adaptable for use in a wide range of spectrometers.”
Once this prototype was identified, the company worked in close collaboration with Specac, a manufacturer whose long history of supplying bespoke spectroscopy solutions, accessories and services made it perfectly positioned to help improve the platform’s performance and ensure its timely delivery. Mark continues: “As our clinical studies proceeded, we asked Specac to take our prototype and carry out the necessary production engineering, and sourcing of components for the routine manufacture of the units. The company was ideally suited to do this based on its experience in the volume manufacture of its excellent Quest units. Throughout, Specac has been an enthusiastic and highly motivated partner and we are very pleased with the function and improved aesthetics of the final ATR-Indexer, which we now call the Dxcover Autosampler.”
In two pioneering clinical studies, the Dxcover® Brain Cancer Liquid Biopsy has been shown to both discriminate between patients with a recent brain tumor diagnosis and asymptomatic controls, and identify gliomas as small as 0.2 cm3. Encouraged by these results, the platform is now set to be extended to detect other forms of cancer through the development of the Dxcover® Cancer Liquid Biopsy, a multi-cancer early detection test.
Hegarty is in no doubt about the future clinical implementation of Dxcover’s approach. “The Dxcover platform will help clinicians detect cancer earlier, improving treatment plans, surgical outcomes, patient prognosis and quality of life,” he shares. “The remaining challenges are those of any diagnostic test, particularly the timely and successful conclusion of clinical studies and obtaining CE-IVDR and FDA regulatory approvals.”
He concludes: “We see this technology as the future of cancer diagnostics, providing a range of first-line tests to assist clinicians in making every day count in the fight against cancer and other diseases.”
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1. Theakstone AG, Brennan PM, Jenkinson MD, et al. Rapid Spectroscopic Liquid Biopsy for the Universal Detection of Brain Tumours. Cancers (Basel). 2021
2. Brennan PM, Butler HJ, Christie L, et al. Early diagnosis of brain tumours using a novel spectroscopic liquid biopsy. Brain Commun. 2021