Detection Of Bilirubin Research Articles

Innovative fluorescent ratiometric probe from Oolong tea dreg for highly sensitive bilirubin detection

Bilirubin, a crucial component in heme degradation, is formed during the breakdown of red blood cells in the liver and spleen. Elevated bilirubin levels are closely associated with jaundice and serve as markers for various blood and liver-related disorders. Detection of BR has been approached through various methods with fluorescent methods gaining prominence due to their exceptional sensitivity, rapid response, and precision. Among the fluorescence methods, carbon dots have emerged as versatile optical probes, known for their unique optical properties, low toxicity, and ease of synthesis. However, carbon dots typically exhibit a single emission peak, limiting accuracy due to vulnerability to external interferences. To overcome this limitation, probes featuring multiple independent emission signals are preferred. Chlorophyll, abundant in nature and sourced from biomass, is recognized for its safe and fluorescent properties, making it a secure choice for fluorescence-based sensing. This study introduces an innovative approach utilizing Oolong tea dreg as a source of chlorophyll for creating a fluorescent probe to detect bilirubin. Chlorophyll was partially converted into carbon dots using a combination of extraction and hydrothermal techniques, producing a ratiometric probe with two emission signals. The fluorescence of the probe was quenched in the presence of the bilirubin through the inner filter effect. The proposed probe exhibited outstanding selectivity and a low limit of detection (0.8 µM) for bilirubin. Furthermore, the probe demonstrated satisfactory recovery rates when tested with artificial urine and human urine samples.

Low-Concentration Bilirubin Detection Based on Photothermal Effect With Parallel Vernier Effect of Optical Fiber Fabry–Pérot Cavity

Low-Concentration Bilirubin Detection Based on Photothermal Effect With Parallel Vernier Effect of Optical Fiber Fabry–Pérot Cavity

2D MoS2 plasmonic nanocavity based SERS platform for bilirubin detection

Although various methods can be used to detect bilirubin at the micromolar level, achieving reliable detection in the sub-nanomolar range remains challenging. Sensitivity at these ultralow levels is vital, as new evidence strongly associates bilirubin with chronic heart, lung, and neurological disorders. This accuracy is also essential for creating diagnostic protocols that can efficiently track bilirubin levels, assisting in managing related conditions. Such advancements will lead to enhanced diagnostic tools and methods, enabling more precise bilirubin monitoring in clinical environments. Here, the aforesaid blind-spot is addressed by utilizing surface enhanced Raman spectroscopy (SERS) as fingerprint technique to detect bilirubin concentrations as low as 0.1 nM. A plasmonically active 2D MoS2 based SERS substrate is formulated and optimized for single step SERS sensing of bilirubin. Plasmonic cavity based approach is utilized to circumvent the problem related to fluorescent background overwhelming the SERS signal. The 2D MoS2 based SERS platform shows threefold enhancement of scattering in comparison to the traditional gold nanoparticle on Si/SiO2 approach. The Raman signature of bilirubin is calibrated by taking citrate as a stable reference analyte and is shown to vary linearly with logarithmic concentration across the picomolar to micromolar range.

Diaper-based wearable SERS sensing system with a silver nano dual-structure composite hydrogel for the detection of biomarkers and pH in urine

Wearable sensors are essential for continuous monitoring of an individual’s health status to enable personalized health management. Urine as a typical non-invasive biological fluid is rich in biological information. Although diaper-based biosensors have been developed, the development of wearable sensors for multiple biomarkers in urine remains a major challenge to be explored. In this paper, a hydrogel SERS sensor consisting of two metal nanostructures of silver nanowires (Ag NWs) and silver nanocubes (Ag NCs) was developed and adhered to nappies to form a wearable nappy-based SERS sensor for the rapid and sensitive detection of bio markers (creatinine, uric acid and bilirubin) and pH in urine. The hydrogel’s excellent adsorption and water-locking properties greatly simplify the collection of urine samples. At the same time, its encapsulation effect can effectively maintain the freshness of the urine sample and ensure the accuracy of the test. The introduction of silver nano dual-structure improves the antimicrobial properties of the hydrogel and reduces the risk of infection when the sensor comes into contact with the skin. Moreover, the silver nano dual-structure triggers abundant electromagnetic “hot spots” around intersecting nanojunctions and gaps, which greatly improves SERS sensitivity. For the detection of creatinine, uric acid and bilirubin, the LODs were as low as 0.59 μM, 69 nM, 89 nM. Finally, the urine pH was accurately detected using a functionalized Ag NWs-Ag NCs/CCNF/Gel/PVA hydrogel. This wearable diaper sensor is expected to be used for personal health condition monitoring and holds great promise for effective care of infants, the elderly, and those with limited mobility.

Biosynthesis of copper nanoclusters for fluorescence detection of bilirubin in biofluids.

Copper nanoclusters (Cu NCs) have shown significant attention in sensing of molecular and ionic species. In this work, a single-step biosynthetic approach was introduced for the preparation of fluorescent Cu NCs using Holarrhena pubescens (H.pubescens) leaves extract as a template. The synthesized H.pubescens-Cu NCs act as a nanomolecular probe for the detection of bilirubin in biofluids. The synthesized H.pubescens-Cu NCs displayed highest fluorescence intensity at 454 nm, when excited at 330 nm. Importantly, selective detection of bilirubin was obtained by introducing H.pubescens-Cu NCs as a simple molecular probe. The interaction of bilirubin and H.pubescens-Cu NCs resulted in a remarkable decrease in the emission peak intensity. The developed H.pubescens-Cu NCs-based bilirubin molecular probe has a wide linear range of 0.5-20.00 μM with the limit of detection of 30.54 nM for bilirubin. The promising application of H.pubescens-Cu NCs-based molecular probe was assessed by assaying bilirubin in spiked biofluids.

Selective and sensitive detection of bilirubin by Fe3+-mediated porphyrin red fluorescence "on-off-on" sensing platform

Bilirubin (BR) serves as a crucial clinical marker for jaundice and liver dysfunction, making its quantitative detection amidst numerous biomolecular interferences of paramount importance. In this work, 5, 10, 15, 20-tetrakis(4-methoxycarbonylphenyl)porphyrin (TPPCOOMe) was utilized as the fluorophore, and Fe3+ was used as the mediator to achieve quantitative detection of BR in human serum through the "on-off-on" fluorescence signal change. The non-fluorescent metalloporphyrin complex TPPCOOMe@Fe3+ generated by the interaction between Fe3+ and TPPCOOMe served as the fluorescence sensing platform. With the addition of BR, the good binding ability between BR and Fe3+ released TPPCOOMe into the sensing medium and restored red fluorescence, while creating conditions for the redox reaction between BR and Fe3+. The fluorescence probe exhibited a good linear relationship with BR in the concentration range of 0–8 μM, the detection limit was as low as 14 nM and the response time was 2 min. Furthermore, a test paper strip-based sensor coupled with a smartphone color-read App was employed to test the fluorescence color changes of TPPCOOMe@Fe3+ for BR sensing, and this intelligent sensing platform had been successfully achieved for the actual detection of BR in human serum without the influence of other metal ions and important biomolecules.

Molecule Engineering Metal-Organic Framework-Based Organic Photoelectrochemical Transistor Sensor for Ultrasensitive Bilirubin Detection.

The functionalization of metal-organic frameworks (MOFs) with organic small molecules by in situ postsynthetic modification has garnered considerable attention. However, the precise engineering of recognition sites using this method remains rarely explored in optically controlled bioelectronics. Herein, employing the Schiff base reaction to embed the small molecule (THBA) into a Zr-MOF, we fabricated a hydroxyl-rich MOF on the surface of titanium dioxide nanorod arrays (U6H@TiO2 NRs) to develop light-sensitive gate electrodes with tailored recognition capabilities. The U6H@TiO2 NR gate electrodes were integrated into organic photoelectrochemical transistor (OPECT) sensing systems to tailor a sensitive device for bilirubin (I-Bil) detection. In the presence of I-Bil, coordination effects, hydrogen bonding, and π-π interactions facilitated strong binding between U6H@TiO2 NRs and the target I-Bil. The electron-donating property of I-Bil influenced the gate voltage, enabling precise control of the channel status and modulation of the channel current. The OPECT device exhibited exceptional analytical performance toward I-Bil with wide linearity ranging from 1 × 10-16 to 1 × 10-9 M and a low limit detection of 0.022 fM. Leveraging the versatility of small molecules for boosting the functionalization of materials, this work demonstrates the great potential of the small molecule family for OPECT bioanalysis and holds promise for the advancement of OPECT sensors.

Hydrothermally in-situ grown MoS2 films over different conducting substrates as electrochemical-SERS biosensors

Detection of organic pollutants and biomolecules at very low concentrations is a great challenge for protecting the environment and diagnosis of human health. Noble metal nanomaterials have been employed as active surface-enhanced Raman spectroscopy (SERS) substrates for such detection but suffer with high cost. The two-dimensional (2D) transition-metal dichalcogenides (TMDs) can be used as cost-effective alternative SERS substrates for the detection of organic impurities and biomolecules. Here, we report the hydrothermally synthesized in-situ grown MoS2 films over conducting carbon paper (CCP) and fluorine-doped tin oxide (FTO) coated glass and used them as SERS substrates for the detection of Rhodamine 6G (R6G), vitamin B12 and bilirubin. We observe that hydrothermally in-situ grown MoS2 film over FTO coated glass (MoS2-FTO) shows a better SERS detection limit for studied analytes compared to the in-situ grown MoS2 film over conducting carbon paper (MoS2-CCP). We observe the detection of R6G, vitamin B12, and bilirubin with maximum enhancement factors of 2.42 × 106, 4.18 × 102, and 2.78 × 106, respectively, using MoS2-FTO as SERS substrate. Furthermore, we demonstrate the electrochemical-SERS (EC-SERS) activity of prepared SERS substrates. The MoS2-FTO shows a better EC-SERS signal as compared to MoS2-CCP due to the high conductivity (maximum charge transfer at oxidation potential), strong chemical adsorption, change of orientation, and density of the molecules on the surface of the substrate.

Engineering Tb(III)-functionalized HOF fluorescence sensing system for intelligent visual detection of two biomarkers of hepatocellular carcinoma

Abnormal levels of bilirubin and human serum albumin are precursors to hepatocellular carcinoma and many fatal diseases. Establishing a portable, highly sensitive and intuitive dual biomarker detection method for bilirubin and human serum albumin is important to protect human health. Combined with the excellent photoluminescence properties of lanthanide functionalized hydrogen bond organic framework, a novel ratiometric fluorescence intelligent sensing system was engineered with the outstanding features of large Stokes shifts, high luminous stability and the self-calibration effect of dual emission centers in this paper. With the advantage of high sensitivity, strong stability and strong anti-interference, the simultaneous detection of dual biomarkers was realized successfully. The developed fluorescence sensing system had a wide detection range of bilirubin and human serum albumin (13.5 nM ∼ 30.0 μM and 448 nM ∼ 15.0 μM), low detection limits (7.20 nM and 15.6 nM). Furthermore, the developed sensing system realized the smartphone-assisted fluorescence visual detection of bilirubin and human serum albumin in serum and urine successfully with the detection limit of 85 nM and 163 nM, providing a promising detection strategy for the early diagnosis of hepatocellular carcinoma.

Synthesis of Graphene Quantum Dots (GQDs) from Paddy Straw for Bilirubin Detection

Synthesis of Graphene Quantum Dots (GQDs) from Paddy Straw for Bilirubin Detection

Polymer composite fiber-optic Fabry–Perot cavity sensor based on Ti3C2TX MXene enhanced photothermal effect for low-concentration bilirubin detection

Polymer composite fiber-optic Fabry–Perot cavity sensor based on Ti3C2TX MXene enhanced photothermal effect for low-concentration bilirubin detection

Bimetallic MOF‐Based Fibrous Device for Noninvasive Bilirubin Sensing

AbstractNoninvasive and real‐time detection of bilirubin concentration enables rapid assessment of liver health status and the diagnosis of jaundice‐related diseases. Herein, the study proposes a strategy to uniformly grow bimetallic FeCo metal–organic framework (MOF) films onto the surface of carbonized electrospun nanofibers via a stepwise growth strategy involving an induction effect of oxide nanomembrane prepared by atomic layer deposition, to realize high‐performance flexible nanofiber bilirubin sensors. Compared with monometallic MOF, the FeCo bimetallic MOF can attain a larger specific surface area, thus augmenting the exposed active sites. Furthermore, the synergistic interaction between the bimetallic active sites on the MOF film and the carbonized nanofibers enhances the electronic conduction network, thereby significantly enhancing the catalytic activity of the flexible electrode for bilirubin. The current nanofibers sensor exhibits excellent performance in bilirubin detection, in terms of high sensitivity, large linear detection range, and low detection limit. The synthesis of bimetallic MOF films on flexible fibers holds promise for the development of highly sensitive electrodes for wearable bilirubin detection devices.

Blue emitting fluorescent Cs2ZnCl4 perovskite nanoprobe for the sensing and visual detection of bilirubin-a jaundice biomarker

Lead halide perovskites are an advanced class of materials with high photoluminescence and optoelectronic properties. However their instability towards moisture and lead toxicity hinders their applications especially in biological sensing. Hence the need for novel lead free perovskite nanocrystals are of utmost important. Herein we synthesized a lead free, highly efficient, stable, cost effective Cs2ZnCl4 perovskite nanocrystals (PNCs) and extends its application in biosensing. The PNCs exhibits bright blue fluorescence upon UV irradiation and was able to selectively detect bilirubin (BR) - a clinically important jaundice biomarker. The intense fluorescence emission of the sensor was completely quenched upon the addition of bilirubin. The sensor could detect bilirubin even in the presence of other interfering biomolecules with a good limit of detection of 26.10 nM. The sensor could successively detect BR in human serum samples. Furthermore, for the visual detection of bilirubin, a paper strip sensor was also designed making the sensor more economical and adaptable.

Human serum albumin directed formation of cadmium telluride quantum dots: Applications in biosensing, anti-bacterial activities and cell cytotoxicity measurements

Although cadmium-based quantum dots (QDs) are highly promising candidates for numerous biological applications, their intrinsic toxicity limits their pertinency in living systems. Surface functionalization of QDs with appropriate molecules could reduce the toxicity level. Herein, we have synthesized the smaller sized (1–5 nm) aqueous-compatible biogenic CdTe QDs using human serum albumin (HSA) as a surface passivating agent via a greener approach. HSA-functionalized CdTe QDs have been explored in multiple in vitro sensing and biological applications, namely, (1) sensing, (2) anti-bacterial and (3) anti-cancer properties. Using CdTe-HSA QDs as a fluorescence probe, a simple fluorometric method has been developed for highly sensitive and selective detection of blood marker bilirubin and hazardous Hg2+ ion with a limit of detection (LOD) of 3.38 and 0.53 ng/mL, respectively. CdTe-HSA QDs also acts as a sensor for standard antibiotics, tetracycline and rifampicin with LOD values of 41.34 and 114.99 ng/mL, respectively. Nano-sized biogenic CdTe-HSA QDs have shown promising anti-bacterial activities against both gram-negative, E. coli and gram-positive, E. faecalis strains confirming more effectiveness against E. faecalis strains. The treatment of human cervical cancer cell lines (HeLa cells) with the synthesized QDs reflected the proficient cytotoxic properties of QDs.

Orange-Red-Emitting Carbon Dots for Bilirubin Detection and Its Antibacterial Activity Against Escherichia coli and Staphylococcus aureus.

In this study, orange-red-emitting carbon dots (OR-CDs) were prepared from p-phenylenediamine (p-PDA) and urea as starting precursors through the hydrothermal method. The OR-CDs exhibited bright orange-red fluorescence at 618 nm when excited at 480 nm. The obtained OR-CDs exhibited stable photophysical properties under different physiological conditions. The unique photophysical property of OR-CDs were then utilized for fluorometric determination of bilirubin. The fluorometric assay revealed that the fluorescence intensity of OR-CDs is gradually quenched upon the addition of bilirubin (1-20 μM). The mechanism of fluorescence quenching was evaluated by steady-state fluorescence analysis and time-correlated single photon counting measurements. The OR-CDs showed good selectivity and sensitivity toward bilirubin over other common interfering biomolecules. The present fluorometric assay showed a linear response toward bilirubin between 1 and 10 μM with a limit of detection of 4.80 nM. Further, a fluorescence test cotton swab-based detection probe has been successfully developed by incorporating OR-CDs for the point-of-care detection of bilirubin in biofluids. Furthermore, a light-emitting diode light that emits orange-red light was prepared by embedding the OR-CDs within the poly(vinyl alcohol) polymer matrix. Moreover, the antibacterial activity of OR-CDs was tested against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. The antibacterial efficacy of OR-CDs was demonstrated by various mechanisms, such as reactive oxygen species generation, destruction of cell structure, chemical binding to membrane, and surface wrapping. Interestingly, the survival assay against L929 fibroblast cells exhibits favorable biocompatibility and bioimaging.

Ti3C2TxMXene modified indium tin oxide (ITO) electrode for electrochemical sensing of bilirubin based on a molecularly imprinted pyrrole polymer

In this study for the first time we are developing Ti3C2TxMXene-based molecularly imprinted electrochemical sensor for the detection of bilirubin (BR). Firstly, Ti3C2TxMXene is synthesized by chemical etching and deposited at the ITO electrode surface by drop casting. After that, pyrrole as a monomer is electropolymerized in the presence of a sodium acetate buffer solution containing the BR template to prepare a BR-imprinted electrode. The modification of ITO electrode with Ti3C2TxMXene has not only imparted binding properties to the substrate that are very important for MIP formation but has also rendered excellent electrochemical characteristics to the electrode as monitored by CV, DPV, and EIS techniques. The sensing studies have been performed with synthetic samples that reveal the potential of prepared molecular imprinted electrochemical sensors toward BR detection. The linearity range, limit of detection, and limit of quantification are calculated as 10 μM to 90 μM, 0.197 μM and 0.598 μM, respectively. Selectivity, stability, and reproducibility are also reported for the prepared MIP sensor.

Used High Collimation UV-LEDs With a Miniaturized Optomechanical Device for the Detection of Direct Bilirubin

Used High Collimation UV-LEDs With a Miniaturized Optomechanical Device for the Detection of Direct Bilirubin

DFT, real sample and smartphone studies of fluorescent probe, N-doped carbon quantum dots for sensitive and selective detection of bilirubin

In this investigation, nitrogen-doped carbon quantum dots (NCQDs) were successfully synthesized, showcasing robust fluorescence characteristics and photostability. These NCQDs demonstrated biocompatibility and were utilized as effective sensing agents for bilirubin (BR) detection. Their remarkable Stern-Volmer constant, attributed to exceptional molar absorptivity and photoluminescence quantum yield, rendered them highly proficient in BR sensing. Various analytical techniques such as X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) were employed to characterize the synthesized NCQDs, providing comprehensive insights into their structural, elemental, chemical composition, particle size, morphology, and optical properties. For sensing purposes, UV–Vis, steady-state, and time-resolved fluorescence spectroscopic techniques were utilized. The average particle size of the NCQDs was determined to be approximately 4.5 ± 0.3 nm. Notably, the Stern-Volmer constant (Ksv) for BR sensing from these quantum dots surpassed previously reported values in the literature. A linear relationship between emission intensity ratio and BR concentration within a range of 1.35–14.20 μM was observed. Accurate quantification of BR was achieved with a high Stern-Volmer constant (Ksv) S11 of approximately 7.48 × 105 M-1 and a limit of detection (LOD) of 4.86 μM. Leveraging the NCQDs as fluorescent probes, a highly sensitive and selective BR detection method based on the Förster resonance energy transfer (FRET) mechanism was established, with emission occurring at 360 nm. Density functional theory (DFT) studies supported FRET as the primary mechanism for fluorescence quenching, indicating electron transfer from NCQDs to BR, as evidenced by the energies of the lowest unoccupied molecular orbitals (LUMOs) of both NCQDs and BR. Real sample analyses of BR levels in human serum yielded a recovery range of 94.8 % to 104.21 %, validating the practical applicability of the method. Furthermore, smartphone-based BR detection using NCQDs achieved an LOD of 11.74 µM.

Photo-crosslinked hydrogel as a sensing platform for sensitive detection of free bilirubin in urine samples

In cases of liver lesions or metabolic blockages, the accumulation of bilirubin in the blood can lead to hyperbilirubinemia, resulting in jaundice. Hence, the development of a rapid and highly selective assay strategy for accurately quantifying free bilirubin concentrations in humans is crucial for clinical diagnosis and treatment. In this study, a postsynthetic modification (PSM) strategy was used to obtain UiO-66-PSM (UP) by the aldimine condensation reaction of metal-organic framework UiO-66-NH2 with 2,3,4-trihydroxybenzaldehyde. UP itself possesses strong fluorescent properties. Subsequently, UiO-66-PSM-Fe (UPF) was synthesized by incorporating Fe3+ onto the UP surface using a one-pot method, where the interaction of Fe3+ with UP induced fluorescence quenching. Bilirubin has a strong binding affinity for Fe3+. Therefore, it can react with the UPF, losing Fe3+ and regaining fluorescence, and thus realizing the detection of bilirubin. In order to further improve the detection outcome and facilitate the application, UPF was loaded onto gelatin methacryloyl hydrogel to construct a fluorescence sensor. This enabled highly sensitive determination of bilirubin with a method limit of detection of 5.67 pM. Furthermore, genuine human urine samples were analyzed, demonstrating the practical application of the assay in discovering human health conditions associated with bilirubin.

Spectral analysis with highly collimated mini-LEDs as light sources for quantitative detection of direct bilirubin

Because the human eye cannot visually detect the results of direct bilirubin test papers accurately and quantitatively, this study proposes four different highly collimated mini light-emitting diodes (HC mini-LEDs) as light sources for detection. First, different concentrations of bilirubin were oxidized to biliverdin by FeCl3 on the test paper, and pictures were obtained with a smartphone. Next, the red, green, and blue (RGB) channels of the pictures were separated to average grayscale values, and their linear relationship with the direct bilirubin concentration was analyzed to detect bilirubin on the test paper noninvasively and quantitatively. The experimental results showed that when green HC mini-LEDs were used as the light sources and image analysis was performed using the G channel, for a direct bilirubin concentration range of 0.1–2 mg/dL, the G channel determination coefficient (R2) reached 0.9523 and limit of detection was 0.459 mg/dL. The detection method proposed herein has advantages such as rapid analysis, noninvasive detection, and digitization according to RGB grayscale changes in the images of the detection test paper.