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Rapid optofluidic detection of biomarkers for traumatic brain injury via surface-enhanced Raman spectroscopy

Abstract

Current technologies for the point-of-care diagnosis of traumatic brain injury (TBI) lack sensitivity, require specialist handling or involve complicated and costly procedures. Here, we report the development and testing of an optofluidic device for the rapid and label-free detection, via surface-enhanced Raman scattering (SERS), of picomolar concentrations of biomarkers for TBI in biofluids. The SERS-active substrate of the device consists of electrohydrodynamically fabricated submicrometre pillars covered with a plasmon-active nanometric gold layer, integrated in an optofluidic chip. We show that the device can detect N-acetylasparate in finger-prick blood samples from patients with TBI, and that the biomarker is released immediately from the central nervous system after TBI. The simplicity, sensitivity and robustness of SERS-integrated optofluidic technology might eventually help the triaging of TBI patients and assist clinical decision making at point-of-care settings.

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Fig. 1: Optimized biodiagnostic platforms.
Fig. 2: Analytical and computational quantification of TBI-indicative biomarkers with optofluidic SERS device.
Fig. 3: Temporal profiling of NAA blood plasma levels post TBI.
Fig. 4: Rapid POC microengineered device technology for TBI biodiagnostics.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated in this study and the source data for the figures are available on figshare at https://doi.org/10.6084/m9.figshare.11302364.v2.

Code availability

The custom MATLAB code can be downloaded from https://gitlab.com/djsmithbham/medtech_projections.

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Acknowledgements

We acknowledge funding from the Wellcome Trust (grant no. 174ISSFPP), the Royal Academy of Engineering (grant no. RF1415\14\28) and the National Institute for Health Research (grant no. DTAARGCQ19497). P.G.O. is a Royal Academy of Engineering Research Fellowship holder. The authors also thank M. J. Rowney and F. M. Colacino for helpful discussions about the technology and insights into classification analyses. Components of the developed device were fabricated using the facilities at the Cavendish Laboratory at the Department of Physics and the Nanoscience Centre for Fabrication, University of Cambridge.

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P.G.O. and A.B. conceptualized the study and designed the project and the experiments with J.J.S.R. J.J.S.R. fabricated the SERS substrates and the optofluidic devices and performed imaging with P.G.O. J.J.S.R. performed material and device characterization, D.J.S. performed the computational and statistical data analysis and classification and D.J.D. carried out the MRI and 1H-MRS data collection and the corresponding data analysis. V.D.-P. and D.J.D. collected and coordinated the clinical samples and, with A.B., established the ethics for this study. J.J.S.R., V.D.-P. and P.G.O. prepared the schematics and images and J.J.S.R. and P.G.O. carried out device engineering and optimization. J.J.S.R. and V.D.P. performed tests on the clinical samples and the corresponding statistical analyses, and analysed the data with P.G.O. All authors carried out the data analysis on the corresponding parts of the study. J.J.S.R., A.B. and P.G.O. wrote the manuscript. All authors reviewed and commented on the manuscript.

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Correspondence to Jonathan J. S. Rickard or Pola Goldberg Oppenheimer.

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Rickard, J.J.S., Di-Pietro, V., Smith, D.J. et al. Rapid optofluidic detection of biomarkers for traumatic brain injury via surface-enhanced Raman spectroscopy. Nat Biomed Eng 4, 610–623 (2020). https://doi.org/10.1038/s41551-019-0510-4

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