Development and validation of hybrid Brillouin-Raman spectroscopy for non-contact assessment of mechano-chemical properties of urine proteins as biomarkers of kidney diseases

Abduzhappar Gaipov, Zhandos Utegulov, Rostislav Bukasov, Duman Turebekov, Pavel Tarlykov, Zhannur Markhametova, Zhangatay Nurekeyev, Zhanar Kunushpayeva, Alisher Sultangaziyev, Abduzhappar Gaipov, Zhandos Utegulov, Rostislav Bukasov, Duman Turebekov, Pavel Tarlykov, Zhannur Markhametova, Zhangatay Nurekeyev, Zhanar Kunushpayeva, Alisher Sultangaziyev

Abstract

Background: Proteinuria is a major marker of chronic kidney disease (CKD) progression and the predictor of cardiovascular mortality. The rapid development of renal failure is expected in those patients who have higher level of proteinuria however, some patients may have slow decline of renal function despite lower level of urinary protein excretion. The different mechanical (visco-elastic) and chemical properties, as well as the proteome profiles of urinary proteins might explain their tubular toxicity mechanism. Brillouin light scattering (BLS) and surface enhanced Raman scattering (SERS) spectroscopies are non-contact, laser optical-based techniques providing visco-elastic and chemical property information of probed human biofluids. We proposed to study and compare these properties of urinary proteins using BLS and SERS spectroscopies in nephrotic patient and validate hybrid BLS-SERS spectroscopy in diagnostic of urinary proteins as well as their profiling. The project ultimately aims for the development of an optical spectroscopic sensor for rapid, non-contact monitoring of urine samples from patients in clinical settings.

Methods: BLS and SERS spectroscopies will be used for non-contact assessment of urinary proteins in proteinuric patients and healthy subjects and will be cross-validated by Liquid Chromatography-Mass Spectrometry (LC-MS). Participants will be followed-up during the 1 year and all adverse events such as exacerbation of proteinuria, progression of CKD, complications of nephrotic syndrome, disease relapse rate and inefficacy of treatment regimen will be registered referencing incident dates. Associations between urinary protein profiles (obtained from BLS and SERS as well as LC-MS) and adverse outcomes will be evaluated to identify most unfavored protein profiles.

Discussion: This prospective study is focused on the development of non-contact hybrid BLS - SERS sensing tool and its clinical deployment for diagnosis and prognosis of proteinuria. We will identify the most important types of urine proteins based on their visco-elasticity, amino-acid profile and molecular weight responsible for the most severe cases of proteinuria and progressive renal function decline. We will aim for the developed hybrid BLS - SERS sensor, as a new diagnostic & prognostic tool, to be transferred to other biomedical applications.

Trial registration: The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT04311684). The date of registration was March 17, 2020.

Keywords: Biochemical; Brillouin light scattering; Chemical; Non-contact diagnostics; Proteinuria; Raman scattering; SERS; Urine proteomics; Viscoelastic.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram illustrating study design, tasks and procedures. SERS: surface enhanced Raman scattering, LC-MS: Liquid Chromatography-Mass Spectrometry, GFR: glomerular filtration rate
Fig. 2
Fig. 2
Schematic demonstration of BLS Spectroscopy using scanning 6-pass TFPI coupled with confocal microscope. M: Mirror, F: Filter, L: Lens or Objective, IL: Imaging Lens, BS: Beam Splitter, CCD: Charge-Coupled Device, TFPI: tandem Fabry-Perot interferometer, PR: prism, PMT: photo-multiplying tube
Fig. 3
Fig. 3
Schematic demonstration of Raman Spectroscopy. M: Mirror, F: Filter, L: Lens or Objective, BS: Beam Splitter, DM: Dichroic Mirror, G: Grating, CCD: Charge-Coupled Device
Fig. 4
Fig. 4
Schematic demonstration of hybrid BLS-Raman Micro-Spectroscopy sensing system. M: Mirror, F: Filter, L: Lens or Objective, CL: Cylindrical Lens, IL: Imaging Lens, BS: Beam Splitter, PBS: Polarizing Beam Splitter, DM: Dichroic Mirror, SMF: Single Mode Fiber, G: Grating, FPE: Fabry-Perot Etalon, CCD: Charge-Coupled Device, VIPA: virtual image phase array, QWT: quarter-wave plate

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