silicon and Hepatitis-B

The prevalence of hepatitis B virus (HBV) is a global healthcare threat, particularly chronic hepatitis B (CHB) that might lead to hepatocellular carcinoma (HCC) should not be neglected. Although many types of HBV diagnosis detection methods are available, some technical challenges, such as the high cost or lack of practical feasibility, need to be overcome. In this study, the polycrystalline silicon nanowire field-effect transistors (pSiNWFETs) were fabricated through commercial process technology and then chemically functionalized for sensing hepatitis B virus surface antigen (HBsAg) and hepatitis B virus X protein (HBx) at the femto-molar level. These two proteins have been suggested to be related to the HCC development, while the former is also the hallmark for HBV diagnosis, and the latter is an RNA-binding protein. Interestingly, these two proteins carried opposite net charges, which could serve as complementary candidates for evaluating the charge-based sensing mechanism in the pSiNWFET. The measurements on the threshold voltage shifts of pSiNWFETs showed a consistent correspondence to the polarity of the charges on the proteins studied. We believe that this report can pave the way towards developing an approachable tool for biomedical applications.

Topics: Carcinoma, Hepatocellular; Delivery of Health Care; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Liver Neoplasms; Nanowires; Silicon; Trans-Activators; Viral Regulatory and Accessory Proteins

In spite of the rapid developments in various nanosensor technologies, it still remains challenging to realize a reliable ultrasensitive electrical biosensing platform which will be able to detect multiple viruses in blood simultaneously with a fairly high reproducibility without using secondary labels. In this paper, we have reported quantitative differentiation of Hep-B and Hep-C viruses in blood using nanoporous silicon oxide immunosensor array and artificial neural network (ANN). The peak frequency output (f

Topics: Antibodies, Immobilized; Biosensing Techniques; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Immunoassay; Limit of Detection; Nanopores; Neural Networks, Computer; Oxides; Silicon

Highly sensitive solution immersed silicon (SIS) biosensors were developed for detection of hepatitis B virus (HBV) infection in the early stage. The ultrasensitivity for overlayer thickness at the nonreflecting condition for the p-polarized wave is the basis of SIS sensing technology. The change in thickness due to biomolecular interactions and change in refractive index of the surrounding buffer medium were assessed simultaneously using two separate ellipsometric parameters (Ψ and Δ), respectively, from a single sensing spot. A direct antigen-antibody affinity assay was used to detect and quantify hepatitis B surface antigen (HBsAg), which is the early stage biomarker for HBV infection. The detection limit of 10 pg/ml was achieved for HBsAg in the human blood serum, which is comparable with the results of enzyme-linked immunosorbent assay and other hybrid assays. The SIS sensor's response time was less than 10 min. The SIS sensors exhibit excellent stability and high signal-to-noise ratio, and are cost-effective, which makes them a suitable candidate for point-of-care applications.

Topics: Biosensing Techniques; Cost-Benefit Analysis; Hepatitis B; Hepatitis B Surface Antigens; Humans; Point-of-Care Systems; Silicon; Time Factors

Percutaneous immune method is becoming an attractive alternative for DNA vaccine as a lot of antigen presenting cells are existed in the viable epidermis. However, due to the barrier function of stratum corneum, it would be hard for DNA vaccine to reach the viable epidermis of the skin. In order to deliver the DNA vaccine successfully cross the stratum corneum, pentagram silicon microneedle array was prepared in this study, and fluorescently labeled nanoparticle was taken as the model to observe the situation inside the skin processed by microneedle. Via microneedle nanoparticles could enter the skin through the micro-channel (diameter about 20-30 µm) and its amount is greatly larger than that enter though the hair follicle of intact skin. A new type of gene vector Pluronic P123-modified polyethyleneimine (P123-PEI) was synthesized by high molecular weight polyethylenimine and Pluronic P123 with the molar ratio of 1 : 1 to take the advantage of P123-PEI as low cytotoxicity and high transfection efficiency. Mice were immunized percutaneously with Hepatitis B DNA vaccine/P123-PEI nano-complexes by microneedle. The humoral and cellular immunity generated in percutaneously immunized mice through microneedle array by Hepatitis B DNA vaccine/P123-PEI nano-complex was significantly higher than that of DNA vaccine intramuscular administration.

Topics: Administration, Cutaneous; Animals; Antibodies, Viral; Antigens, Viral; Female; Genetic Vectors; Hepatitis B; Hepatitis B Vaccines; Immunoglobulin G; Interferon-gamma; Mice; Mice, Inbred C57BL; Microinjections; Nanoparticles; Needles; Particle Size; Poloxalene; Polyethyleneimine; Silicon; Spleen; Vaccines, DNA

Silicon-on-isolator-nanowires (SOI-NWs) were used for the label-free, real-time biospecific detection of the hepatitis B marker HBsAg and cancer marker α-fetoprotein (AFP). Specific protein-protein recognition was carried out using individual NWs that were functionalized with antibodies. To solve the problem of non-specific binding of target protein molecules to the sensor element the use of a reference NW with immobilized antibodies against non-target proteins was proposed. Using individual SOI-NW surface functionalization allowed the fabrication of a NW array, containing working NWs and reference NWs within one chip. It was shown that this approach allows us to reach a detection limit up to 10(-14) and 10(-15) M for HBsAg and AFP, respectively. Our investigations also allowed us to reveal the influence of the charged state of the target protein molecules and antibodies in solutions with various pH values on the target protein detection limit. A high sensitivity NW-detector is of interest for the creation of diagnosticums for hepatitis B and for the early stages of cancer diseases.

Topics: alpha-Fetoproteins; Animals; Biomarkers, Tumor; Biosensing Techniques; Electric Impedance; Hepatitis B; Hepatitis B Surface Antigens; Humans; Nanowires; Silicon

The polymerase chain reaction (PCR) is widely used to amplify a small amount of DNA in samples for genetic analysis. Rapid and accurate amplification is prerequisite for broad applications including molecular diagnostics of diseases, food safety, and biological warfare tests. We have developed a rapid real-time micro-scale chip-based PCR system, which consists of six individual thermal cycling modules capable of independent control of PCR protocols. The PCR volume is 1 microl and it takes less than 20 min to complete 40 thermal cycles. To test utility of a chip-based PCR system as a molecular diagnostic device, we have conducted the first large-scale clinical evaluation study. Three independent clinical evaluation studies (n = 563) for screening the hepatitis B virus (HBV) infection, the most popular social epidemic disease in Asia, showed an excellent sensitivity, e.g. 94%, and specificity, e.g. 93%, demonstrating micro-scale chip-based PCR can be applied in molecular diagnostics.

Topics: DNA, Viral; Hepatitis B; Hepatitis B virus; Humans; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity; Silicon