Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Enhanced localized plasmonic detections using partially-embedded gold nanoparticles and ellipsometric measurements

A cost-effective, stable and ultrasensitive localized surface plasmon resonance (LSPR) sensor based on gold nanoparticles (AuNPs) partially embedded in transparent substrate is presented. Partially embedded AuNPs were prepared by thermal annealing of gold thin films deposited on glass at a temperature close to the glass transition temperature of the substrate. Annealed samples were optically characterized by using spectroscopic ellipsometry and compare with theoretical modeling to understand the optical responses from the samples. By combining the partially-embedded AuNPs substrate with a microfluidic flow cell and dove prism in an ellipsometry setup, an ultrasensitive change in the LSPR signal can be detected. The refractive index sensitivity obtained from the phase measurement is up to 1938 degrees/RIU which is several times higher than that of synthesized colloidal gold nanoparticles. The sample is further used to investigate the interactions between primary and secondary antibodies. The bio-molecular detection limit of the LSPR signal is down to 20 pM. Our proposed sensor is label free, non-destructive, with high sensitivity, low cost, and easy to fabricate. These features make it feasible for commercialization in biomedical applications

NANOSCIENCE IN DIAGNOSTICS: A SHORT REVIEW

Nanoscience is at the leading edge of the rapidly developing field of nanotechnology. Nanosciences and nanotechnology are transforming a wide array of products and services that have the potential to enhance the practice of medicine and improve public health. Several areas of medical care are already benefiting from the advantages that nanotechnology can offer. Applications of nanoscience are in biotechnology, medicine, pharmaceuticals, physics, material science and also electronics. Nanotechnology extends the limits of molecular diagnostics to the nanoscale. Nanotechnology on a chip is one more dimension of microfluidic/lab on a chip technology. We still suffer serious and complex illnesses like cancer, cardiovascular diseases, multiple sclerosis, Alzheimer’s and Parkinson’s disease, and diabetes as well as different kinds of serious inflammatory or infectious diseases (e.g. HIV). It is of extreme importance to face these diseases with appropriate means. The interplay between nanoscience and biomedicine is the hallmark of current scientific research worldwide. The use of nanoscience may open new vistas of improving the effectiveness and efficiency of medical diagnosis and therapeutics, so called nanomedicine. An appealing example is the use of quantum dots as fluorescent labels. Despite recent progress in the treatment of cancer, the majority of cases are still diagnosed only after tumors metastasize, leaving the patient with a grim prognosis. Nanotechnology is in a unique position to transform cancer diagnostics and to produce a new generation of biosensors and medical imaging techniques with higher sensitivity and precision of recognition. Novel nanotechnologies can complement and augment existing genomic and proteomic techniques employed to analyze variations across different tumor types, thus offering the potential to distinguish between normal and malignant cells. This brief review tries to reiterate the most contemporary developments in the field of applied nanoscience, particularly in their relevance in diagnosis of various diseases and discuss their future prospects

Progress in fluorescence biosensing and food safety towards point-of-detection (PoD) system

The detection of pathogens in food substances is of crucial concern for public health and for the safety of the natural environment. Nanomaterials, with their high sensitivity and selectivity have an edge over conventional organic dyes in fluorescent-based detection methods. Advances in microfluidic technology in biosensors have taken place to meet the user criteria of sensitive, inexpensive, user-friendly, and quick detection. In this review, we have summarized the use of fluorescence-based nanomaterials and the latest research approaches towards integrated biosensors, including microsystems containing fluorescence-based detection, various model systems with nano materials, DNA probes, and antibodies. Paper-based lateral-flow test strips and microchips as well as the most-used trapping components are also reviewed, and the possibility of their performance in portable devices evaluated. We also present a current market-available portable system which was developed for food screening and highlight the future direction for the development of fluorescence-based systems for on-site detection and stratification of common foodborne pathogens

Nanotechnology in Bladder Cancer: Diagnosis and Treatment

Bladder cancer (BC) is the second most common cancer of the urinary tract in men and the fourth most common cancer in women, and its incidence rises with age. There are many conventional methods for diagnosis and treatment of BC. There are some current biomarkers and clinical tests for the diagnosis and treatment of BC. For example, radiotherapy combined with chemotherapy and surgical, but residual tumor cells mostly cause tumor recurrence. In addition, chemotherapy after transurethral resection causes high side effects, and lack of selectivity, and low sensitivity in sensing. Therefore, it is essential to improve new procedures for the diagnosis and treatment of BC. Nanotechnology has recently sparked an interest in a variety of areas, including medicine, chemistry, physics, and biology. Nanoparticles (NP) have been used in tumor therapies as appropriate tools for enhancing drug delivery efficacy and enabling therapeutic performance. It is noteworthy, nanomaterial could be reduced the limitation of conventional cancer diagnosis and treatments. Since, the major disadvantages of therapeutic drugs are their insolubility in an aqueous solvent, for instance, paclitaxel (PTX) is one of the important therapeutic agents utilized to treating BC, due to its ability to prevent cancer cell growth. However, its major problem is the poor solubility, which has confirmed to be a challenge when improving stable formulations for BC treatment. In order to reduce this challenge, anti-cancer drugs can be loaded into NPs that can improve water solubility. In our review, we state several nanosystem, which can effective and useful for the diagnosis, treatment of BC. We investigate the function of metal NPs, polymeric NPs, liposomes, and exosomes accompanied therapeutic agents for BC Therapy, and then focused on the potential of nanotechnology to improve conventional approaches in sensing

Enzymatisch generiertes Nanopartikelwachstum für Biochipsysteme in der Vor-Ort-Analytik

Durch die stetig wachsende Anzahl an diagnostisch relevanten Biomolekülen, wie DNA, RNA oder Proteinen, steht die heutige Bioanalytik vor der Herausforderung die unterschiedlichen Analyten selektiv mit spezifischen Verfahren nachzuweisen. Das zunehmende Wissen über die verschiedenartigen Wechselwirkungen die diese Biomoleküle untereinander ausführen, ermöglicht es Bakterien, Viren, Pilze, Pflanzen oder tierische Proben auf biomolekularer Ebene nachzuweisen und somit Krankheiten, Kontaminationen oder auch Mutationen zu diagnostizieren. Die steigende Nachfrage nach kostengünstigen und robusten Nachweissystemen für die Bioanalytik erfordert die Entwicklung neuartiger Geräte, die ähnlich wie bei einem Schwangerschaftstest, die Analyse relevanter Biomoleküle schnell und direkt vor Ort ermöglichen. Zusätzlich soll ein deutlich reduzierter manueller Aufwand zu einer einfachen Handhabung der entwickelten Systeme auch durch den geschulten Laien führen. Die dazu notwendige Automatisierung führt zu einem autarken Verfahren, das mobil und transportabel auch außerhalb spezialisierter Labore und dadurch am Ort des Geschehens eingesetzt werden kann. Durch ihre Fähigkeit zum Hochdurchsatz, die Parallelität und die Flexibilität stellen Biochips eine viel versprechende Plattform für die Entwicklung von point-of-care-Geräten dar. Diese Arbeit befasst sich mit Untersuchungen chipbasiertes Verfahren zum Nachweis von Biomolekülen zur Realisierung eines so genannten point-of care Systems für die Umsetzung einer Vor-Ort-Analytik. Dazu wird ein neuartiges enzymatisches Verfahren zur Synthese von Metallnanopartikeln mit einer elektrischen Detektion der biomolekularen Wechselwirkungen verwendet. Mit dieser Methode sind viele der nachgefragten Ziele für ein point-of-care-fähiges System umsetzbar. Im Vergleich mit herkömmlichen Biochipsystemen, die auf einem optischen Nachweisverfahren beruhen, ermöglicht die elektrische Detektion ein kostengünstiges und robustes System. Durch ein einfaches Messverfahren, wie eine Gleichstrommessung kann mit Hilfe einer robusten Auswertetechnik ein transportables und störungsunanfälliges Nachweissystem konstruiert werden

Helium beam shadowing for high spatial resolution patterning of antibodies on microstructured diagnostic surfaces

We have developed a technique for the high-resolution, self-aligning, and high-throughput patterning of antibody binding functionality on surfaces by selectively changing the reactivity of protein-coated surfaces in specific regions of a workpiece with a beam of energetic helium particles. The exposed areas are passivated with bovine serum albumin (BSA) and no longer bind the antigen. We demonstrate that patterns can be formed (1) by using a stencil mask with etched openings that forms a patterned exposure, or (2) by using angled exposure to cast shadows of existing raised microstructures on the surface to form self-aligned patterns. We demonstrate the efficacy of this process through the patterning of anti-lysozyme, anti-Norwalk virus, and anti-Escherichia coli antibodies and the subsequent detection of each of their targets by the enzyme-mediated formation of colored or silver deposits, and also by binding of gold nanoparticles. The process allows for the patterning of three-dimensional structures by inclining the sample relative to the beam so that the shadowed regions remain unaltered. We demonstrate that the resolution of the patterning process is of the order of hundreds of nanometers, and that the approach is well-suited for high throughput patterning