A graphene oxide-gold nanostar hybrid based-paper biosensor for label-free SERS detection of serum bilirubin for diagnosis of jaundice. Pan Xiang,Li Linhu,Lin Hangduo,Tan Jiayi,Wang Haitao,Liao Mengling,Chen Caiju,Shan Beibei,Chen Yingfan,Li Ming Biosensors & bioelectronics We report a paper-based surface-enhanced Raman spectroscopy (SERS) biosensor integrating the enrichment capability, namely enPSERS biosensor, for the sensitive, label-free detection of free bilirubin in blood serum for the accurate diagnosis of jaundice and its related diseases. This biosensor comprises multifunctional graphene oxide-plasmonic gold nanostar (GO-GNS) hybrids decorated on the filter paper, which integrates the high sensitivity of SERS detection, enrichment for serum bilirubin and fluorescence superquenching capability of GO-GNS hybrids for sensitive detection of serum bilirubin. The study of adsorption kinetics reveals that both electrostatic and π-π interactions between the GO-GNS hybrids and targets are responsible for the enrichment of bilirubin, and the adsorption process follows the pseudo-second-order kinetic model. The results of SERS detection of bilirubin in blood serum show two differential linear response ranges from 5.0 to 150 μM and 150-500 μM with the detection limit as low as 0.436 μM. The comparison of the results obtained from our present enPSERS biosensor with the commercial diazo reaction method for determination of free bilirubin in blood serum reveals the clinical effectiveness and suitability of the developed paper-based SERS biosensor. We believe that this sensitive and label-free SERS biosensor holds considerable promise for clinical translation in accurate diagnosis of jaundice. 10.1016/j.bios.2019.111713

Selective and sensitive detection of free bilirubin in blood serum using human serum albumin stabilized gold nanoclusters as fluorometric and colorimetric probe. Santhosh Mallesh,Chinnadayyala Somasekhar R,Kakoti Ankana,Goswami Pranab Biosensors & bioelectronics We report here a fluorescence quenching based non-enzymatic method for sensitive and reliable detection of free bilirubin in blood serum samples using human serum albumin (HSA) stabilized gold nanoclusters (HSA-AuNCs) as fluorescent probe. The fluorescence of the nanoclusters was strongly quenched by bilirubin in a concentration dependent manner by virtue of the inherent specific interaction between bilirubin and HSA. A strong binding constant of 0.55×10(6) L mole(-1) between the HSA-AuNC and bilirubin was discerned. The nano clusters each with size ~1.0 nm (in diameter) and a core of Au18 were homogeneously distributed in HSA molecules as revealed from the respective high resolution transmission electron microscopic and mass spectroscopic studies. The fluorescence quenching phenomena which obeyed a simple static quenching mechanism, was utilized for interference free detection of bilirubin with minimum detection limit (DL) of 248±12 nM (S/N=3). The fluorescence response of HSA-AuNCs against bilirubin was practically unaltered over a wide pH (6-9) and temperature (25-50 °C) range. Additionally, peroxidase-like catalytic activity of these nanoclusters was exploited for colorimetric detection of bilirubin in serum sample with a DL of 200±19 nM by following the decrease in absorbance (at λ440 nm) of the reaction and its rate constant (Kp) of 2.57±0.63 mL μg(-1) min(-1). Both these fluorometric and colorimetric methods have been successfully used for detection of free bilirubin in blood serum samples. 10.1016/j.bios.2014.04.003

Paper-based device for the colorimetric assay of bilirubin based on in-situ formation of gold nanoparticles. Edachana Resmi P,Kumaresan Abishek,Balasubramanian Vidhya,Thiagarajan Ramachandran,Nair Bipin G,Thekkedath Gopalakrishnan Satheesh Babu Mikrochimica acta A paper-based colorimetric assay for the determination of bilirubin has been developed. The method is based on the in-situ reduction of chloroauric acid to form gold nanoparticles. A chromatographic paper was patterned using a wax printer. Chloroauric acid was drop-cast onto the reagent zone. In the presence of bilirubin, gold(III) ions are reduced and form gold nanoparticles. This leads to a color change from yellow to purple. The intensity of the purple color (peak at 530 nm) increases with bilirubin concentration in the 5.0 to 1000 mg L range. The detection limit is 1.0 mg L. For the quantification of bilirubin, images were captured using a digital camera, and data were processed with the help of machine learning-based supervised prediction using Random Forest classification. The method was applied to the determination of bilirubin in urine samples. The spiked urine samples exhibit more than 95% recovery. Graphical abstractSchematic representation of the paper-based colorimetric assay for the detection of bilirubin based on the in-situ formation of gold nanoparticles. A color band is generated for visual interpretation and used for the testing of bilirubin in urine. 10.1007/s00604-019-4051-z

Electrochemical sensor for the discrimination of bilirubin in real human blood based on Au nanoparticles/ tetrathiafulvalene -carboxylate functionalized reduced graphene oxide 0D-2D heterojunction. Zheng Zhixiang,Feng Qingliang,Zhu Meijie,Shang Jing,Li Meng,Li Chun,Kou Liangzhi,Zheng Jianbang,Wang Chunming Analytica chimica acta In clinical practice, the excess concentration of bilirubin can trigger diseases such as neonatal jaundice, hepatic failure, septicemia, and so on. The concentration of bilirubin is one of important clinical indexes to evaluate patients with hepatic function disease in clinical practice. Therefore, it is very necessary to develop a rapid detection technique detecting the bilirubin in body fluids. Here, a new electrochemical sensor based on Au nanoparticles/tetrathiafulvalene-carboxylate functionalized reduced grapheneoxide 0D-2D heterojunction(AuNPs/TTF-COOH/RGO) was fabricated for the discrimination of bilirubin in real human blood. The TTF-COOH could effectively repair electron conductivity of RGO nanosheets, decrease interface resistance, and also enhance the dispersity of TTF-COOH/RGO nanosheets in water. What's more, the S atoms of TTF-COOH can bonding the gold nano-particles (AuNPs) to fabricate a 0D-2D heterojunction with excellent biocompatibility and enhanced specific surface area. After bilirubin oxidases were self-assembled on the surface of AuNPs, a specific recognition interface was formed as a sensor for the detection of bilirubin. The heterojunction showed enhanced interface electron transfer rate, excellent biocompatibility, and also prominent electrocatalytic activity for the high efficiency catalysis of bilirubin. The sensor shows a linear response for bilirubin from 2.66 to 83  μmol L and a low detection limit of 0.74 μmol L at 3σ. This work provides one novel approach to detection of bilirubin by functional RGO nanosheets, and broadens the application area of RGO nanosheets in selective catalysis and detection of biomolecule in biological specimens, such as blood, urine. 10.1016/j.aca.2019.04.040

A Gold Nanoclusters Film Supported on Polydopamine for Fluorescent Sensing of Free Bilirubin. Li Zhou,Xiao Wenxiang,Huang Rongen,Shi Yajing,Fang Cheng,Chen Zhencheng Sensors (Basel, Switzerland) Serum bilirubin is an important biomarker for the diagnosis of various types of liver diseases and blood disorders. A polydopamine/gold nanoclusters composite film was fabricated for the fluorescent sensing of free bilirubin. Bovine serum albumin (BSA)-stabilized gold nanoclusters (AuNCs) were used as probes for biorecognition. The polydopamine film was utilized as an adhesion layer for immobilization of AuNCs. When the composite film was exposed to free bilirubin, due to the complex that was formed between BSA and free bilirubin, the fluorescence intensity of the composite film was gradually weakened as the bilirubin concentration increased. The fluorescence quenching ratio (F₀/F) was linearly proportional to free bilirubin over the concentration range of 0.8~50 μmol/L with a limit of detection of 0.61 ± 0.12 μmol/L (S/N = 3). The response was quick, the film was recyclable, and common ingredients in human serum did not interfere with the detection of free bilirubin. 10.3390/s19071726