PMID- 37998324 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20240210 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 12 IP - 22 DP - 2023 Nov 8 TI - Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury. LID - 10.3390/cells12222589 [doi] LID - 2589 AB - Traumatic brain injury (TBI) affects millions of people of all ages around the globe. TBI is notoriously hard to diagnose at the point of care, resulting in incorrect patient management, avoidable death and disability, long-term neurodegenerative complications, and increased costs. It is vital to develop timely, alternative diagnostics for TBI to assist triage and clinical decision-making, complementary to current techniques such as neuroimaging and cognitive assessment. These could deliver rapid, quantitative TBI detection, by obtaining information on biochemical changes from patient's biofluids. If available, this would reduce mis-triage, save healthcare providers costs (both over- and under-triage are expensive) and improve outcomes by guiding early management. Herein, we utilize Raman spectroscopy-based detection to profile a panel of 18 raw (human, animal, and synthetically derived) TBI-indicative biomarkers (N-acetyl-aspartic acid (NAA), Ganglioside, Glutathione (GSH), Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), Cholesterol, D-Serine, Sphingomyelin, Sulfatides, Cardiolipin, Interleukin-6 (IL-6), S100B, Galactocerebroside, Beta-D-(+)-Glucose, Myo-Inositol, Interleukin-18 (IL-18), Neurofilament Light Chain (NFL)) and their aqueous solution. The subsequently derived unique spectral reference library, exploiting four excitation lasers of 514, 633, 785, and 830 nm, will aid the development of rapid, non-destructive, and label-free spectroscopy-based neuro-diagnostic technologies. These biomolecules, released during cellular damage, provide additional means of diagnosing TBI and assessing the severity of injury. The spectroscopic temporal profiles of the studied biofluid neuro-markers are classed according to their acute, sub-acute, and chronic temporal injury phases and we have further generated detailed peak assignment tables for each brain-specific biomolecule within each injury phase. The intensity ratios of significant peaks, yielding the combined unique spectroscopic barcode for each brain-injury marker, are compared to assess variance between lasers, with the smallest variance found for UCHL1 (sigma(2) = 0.000164) and the highest for sulfatide (sigma(2) = 0.158). Overall, this work paves the way for defining and setting the most appropriate diagnostic time window for detection following brain injury. Further rapid and specific detection of these biomarkers, from easily accessible biofluids, would not only enable the triage of TBI, predict outcomes, indicate the progress of recovery, and save healthcare providers costs, but also cement the potential of Raman-based spectroscopy as a powerful tool for neurodiagnostics. FAU - Harris, Georgia AU - Harris G AUID- ORCID: 0000-0001-8826-7057 AD - Advanced Nanomaterials Structures and Applications Laboratories, School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. FAU - Stickland, Clarissa A AU - Stickland CA AD - Advanced Nanomaterials Structures and Applications Laboratories, School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. FAU - Lim, Matthias AU - Lim M AD - Advanced Nanomaterials Structures and Applications Laboratories, School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. FAU - Goldberg Oppenheimer, Pola AU - Goldberg Oppenheimer P AUID- ORCID: 0000-0002-1014-4724 AD - Advanced Nanomaterials Structures and Applications Laboratories, School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. AD - Institute of Healthcare Technologies, Mindelsohn Way, Birmingham B15 2TH, UK. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 174ISSFPP/WT_/Wellcome Trust/United Kingdom GR - EP/Y030206/1/ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231108 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) RN - 0 (Biomarkers) SB - IM MH - Animals MH - Humans MH - Spectrum Analysis, Raman MH - Ubiquitin Thiolesterase MH - *Brain Injuries, Traumatic/diagnosis MH - *Brain Injuries/diagnosis MH - Biomarkers PMC - PMC10670390 OTO - NOTNLM OT - Raman spectroscopy OT - TBI biomarkers OT - acute, sub-acute and chronic phases OT - neurodiagnostics OT - traumatic brain injury COIS- The authors declare no conflict of interest. EDAT- 2023/11/24 12:42 MHDA- 2023/11/27 12:44 PMCR- 2023/11/08 CRDT- 2023/11/24 09:35 PHST- 2023/10/11 00:00 [received] PHST- 2023/11/02 00:00 [revised] PHST- 2023/11/06 00:00 [accepted] PHST- 2023/11/27 12:44 [medline] PHST- 2023/11/24 12:42 [pubmed] PHST- 2023/11/24 09:35 [entrez] PHST- 2023/11/08 00:00 [pmc-release] AID - cells12222589 [pii] AID - cells-12-02589 [pii] AID - 10.3390/cells12222589 [doi] PST - epublish SO - Cells. 2023 Nov 8;12(22):2589. doi: 10.3390/cells12222589.