An intelligent serological SERS test toward early-stage hepatocellular carcinoma diagnosis through ultrasensitive nanobiosensing

Early or very early detection of hepatocellular carcinoma(HCC)is an effective means to resolve the low cure rates,but there currently lacks a method that fulfills clinical requirements.One of the most prospective approaches to detecting early-stage HCC is directly testing a compendium of disease-relevant biomolecules contained within human serum through surface-enhanced Raman scattering(SERS)nanobiosensing and recognizing the biomolecular patterns.We report a novel Si-based bimetallic nanoensembles-functionalized SERS substrate(its analytical enhancement factor reaches 1.47×10^(12))and introduce an ultrasensitive nanobiosensing for capturing the subtle characteristic changes in SERS spectra caused by HCC,hepatitis B,or cirrhosis.Toward early diagnosis,we created an intelligent serological test with this nanobiosensing and the deep learning algorithm to gain key biomolecular phenotypes of early-stage HCC.Using clinical samples from four target populations(normal,HCC,cirrhosis,and hepatitis B),the proof-of-principle result indicates that the test yielded a predictive accuracy of 98.75%on a held-out dataset(randomly drew 4 out of 28 samples per population).On the same held-out dataset,the sensitivity and specificity of the test were both 100%for distinguishing HCC.Such a new-concept liquid biopsy could provide an opportunity for early diagnosis of HCC.

Microcantilever-based Nanomechanical Studies of the Orphan Nuclear Receptor Pregnane X Receptor-Ligand Interactions

Human pregnane X receptor (PXR) is of vital importance in pharmaceutical and exogenous compound metabolism within the body. This provides strong motivation for investigating this orphan receptor’s activation by various pharmaceuticals, xenobiotics, and endocrine disrupting chemicals (EDCs). A nanomechanical transducer is developed to study xenobiotic and EDC interactions with the bioreceptor PXR’s ligand binding domain (LBD). The combination of immobilized LBD PXR with a nanostructured microcantilever (MC) platform allows for the sensitive, label-free study of ligand interaction with the receptor. PXR shows real-time, reversible responses when exposed to a specific pharmaceutical, EDCs, and xenobiotic ligands. Three EDCs binding interactions are tested, which include phthalic acid, nonylphenol, and bisphenol A, with PXR. PXR LBD was exposed to rifampicin, a potent PXR activator, with various injection and recovery times to study their interaction. A two protein array of PXR and estrogen receptor ? (ER-?) directly compares the nanomechanical responses of these receptors with rifampicin on a single platform.

Sensitive biosensing strategy based on functional nanomaterials

The first decade of the 21st century has been labeled as "the sensing decade". The functional nanomaterials offer excellent platforms for fabrication of sensitive biosensing devices, including optical and electronic biosensors. A lot of works have fo- cused on the biofunctionalization of different nanomaterials, such as metal nanoparticles, semiconductor nanoparticles and carbon nanostructures, by physical adsorption, electrostatic binding, specific recognition or covalent coupling. These biofunc- tionalized nanomaterials can be used as catalysts, electronic conductors, optical emitters, carriers or tracers to obtain the ampli- fied detection signal and the stabilized recognition probes or biosensing interface. The designed signal amplification strategies have greatly promoted the development of stable, specific, selective and sensitive biosensors in different fields. This review in- troduces some novel principles and detection strategies in the area of biosensing, based on functional nanomaterials. The gen- eral methods for biofunctionalization of nanomaterials with biomolecules and their biosensing application in immunoassay of protein, DNA detection, carbohydrate analysis and cytosensing are also described.