Fiber enhanced Raman spectroscopic analysis as a novel method for diagnosis and monitoring of diseases related to hyperbilirubinemia and hyperbiliverdinemia

Abstract

Fiber enhanced resonance Raman spectroscopy (FERS) is introduced for chemically selective and ultrasensitive analysis of the biomolecules hematin, hemoglobin, biliverdin, and bilirubin. The abilities for analyzing whole intact, oxygenated erythrocytes are proven, demonstrating the potential for the diagnosis of red blood cell related diseases, such as different types of anemia and hemolytic disorders. The optical fiber enables an efficient light-guiding within a miniaturized sample volume of only a few micro-liters and provides a tremendously improved analytical sensitivity (LODs of 0.5 μM for bilirubin and 0.13 μM for biliverdin with proposed improvements down to the pico-molar range). FERS is a less invasive method than the standard ones and could be a new analytical method for monitoring neonatal jaundice, allowing a precise control of the unconjugated serum bilirubin levels, and therefore, providing a better prognosis for newborns. The potential for sensing very low concentrations of the bile pigments may also open up new opportunities for cancer research. The abilities of FERS as a diagnostic tool are explored for the elucidation of jaundice with different etiologies including the rare, not yet well understood diseases manifested in green jaundice. This is demonstrated by quantifying clinically relevant concentrations of bilirubin and biliverdin simultaneously in the micro-molar range: for the case of hyperbilirubinemia due to malignancy, infectious hepatitis, cirrhosis or stenosis of the common bile duct (1 μM biliverdin together with 50 μM bilirubin) and for hyperbiliverdinemia (25 μM biliverdin and 75 μM bilirubin). FERS has high potential as an ultrasensitive analytical technique for a wide range of biomolecules and in various life-science applications.

The complexity of porphyrin-like pigments in a marine annelid sheds new light on haem metabolism in aquatic invertebrates

“…2) have quite distinct spectra from carotenoids 36 . The assumption of pigments analogous to bilirubin and biliverdin as the main pigments present in E. viridis is supported by the analysis of bile pigments in humans, since the absorption spectra show great similarities, especially the maximum absorption peaks at 400 and 700 nm here found for the green pigments 37 .…”

Chemical Monitoring in Clinical Settings: Recent Developments toward Real-Time Chemical Monitoring of Patients

“…65 Additionally, using Raman to measure the pH of blood via erythrocyte non-invasively in vivo in mice has been proposed. 65 Monitoring the pH of arterial blood allows determination of the acid-base status, and can be performed using a confocal laser tweezers Raman system. Furthermore, Raman spectroscopy can be used for the non-invasive assessment of red blood cells collected from blood donation, and monitor lactate production from these cells during storage periods.…”

Highly Sensitive Detection of the Antibiotic Ciprofloxacin by Means of Fiber Enhanced Raman Spectroscopy

“…The Raman intensity I stokes can be increased by increasing the excitation frequency ω 0 , the laser power I 0 , or the number of molecules N, which contribute to the Raman signal [38]. The last approach is exploited in fiber-enhanced Raman spectroscopy (FERS), where the light is guided in the hollow fiber [38][39][40][41][42][43][44][45][46][47][48] and can strongly interact with the drug molecules over an extended interaction length [49][50][51][52][53][54] (Figure 1). Within the last decades, a lot of effort was invested in studying the fiber enhancement effect of photonic crystal fibers [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73].…”