Carbon nanotube thin film transistors for biomedical applications.

The application of carbon nanotubes (CNTs) has captivated the curiosity of today\u27s experts due to the escalating potential in the field of electronic detection of biomolecules. Their extreme environmental sensitivity and small size make them ideal candidates for future biosensing technologies. Recent studies have shown that the binding of receptor proteins (biomolecules located at the membrane of cells) with their corresponding antibodies immobilized on a carbon nanotube surface causes changes in the electrical properties of carbon nanotubes and have been measured with a carbon nanotube field effect transistor (CNTFET). This specific molecular interaction and sensitivity is promising for the direct detection of live cells in blood. In this study, a biosensor was developed based on carbon nanotube thin film transistors for the purpose of electrically detecting breast cancer cells (MCF-7) in blood. The electrical response of specific and non-specific interactions between anchored antibodies onto the carbon nanotube film surface and breast cancer cells mixed with blood were monitored and recorded. The electrical measurements indicate that devices functionalized with specific antibodies (anti-IGF1R) experience large conductivity drops (~60 %). However for those device printed with non-specific antibodies (anti-IgG), small changes (~10 %) in conductivity are measured. It is postulated that the addition of increasing number of MCF-7cells mixed with blood on a CNT surface functionalized with specific antibodies (anti-IGF1R) acts as a chemical gate modulating the current flow. Biosensing mechanistic studies using a liquid gated CNTFET, confirmed that the specific antibody-receptor binding can be attributed to electrostatic gating effect by which cancer cells can be screened in blood

Biomolecular tuning of electronic transport properties of carbon nanotubes via antibody functionalization

Carbon nanotubes (CNTs) are remarkable solidstate nanomaterials due to their unique electrical and mechanical properties. The electronic properties of nanotubes combined with biological molecules such as proteins could make miniature devices for biological sensing applications. In this paper, the noncovalent interaction of single-wall CNTs with antibodies is presented for its potential applications for detecting overexpressed cell surface receptors in breast cancer cells. The degree of binding of antibodies on CNTs was found to be more than 80% for an extended sampling area by confocal microscopy. The key to achieve such high degree of functionalization is due to the separation of CNTs using surfactants that leads to a high surface area to volume ratio and higher number of active sites for charge transfer that enhance binding. This paper also presents tuning of electronic transport properties of CNTs by monoclonal antibodies that are specific to insulin-like growth factor 1 receptor in breast cancer

Embedded disposable functionalized electrochemical biosensor with a 3D-printed flow cell for detection of hepatic oval cells (HOCs)

Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells. The developed sensor can be easily embedded into the 3D-printed flow cell to allow cells to be exposed continuously to the functionalized surface. The continuous flow is intended to increase capture of most of the target cells in the specimen. Contact angle measurements were performed to characterize the nature and quality of the modified sensor surface, and electrochemical measurements (cyclic voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed method is valuable for capturing rare cells and could provide an effective tool for cancer diagnosis and detection

Graphene Quantum Dot-Based Electrochemical Immunosensors for Biomedical Applications

In the area of biomedicine, research for designing electrochemical sensors has evolved over the past decade, since it is crucial to selectively quantify biomarkers or pathogens in clinical samples for the efficacious diagnosis and/or treatment of various diseases. To fulfil the demand of rapid, specific, economic, and easy detection of such biomolecules in ultralow amounts, numerous nanomaterials have been explored to effectively enhance the sensitivity, selectivity, and reproducibility of immunosensors. Graphene quantum dots (GQDs) have garnered tremendous attention in immunosensor development, owing to their special attributes such as large surface area, excellent biocompatibility, quantum confinement, edge effects, and abundant sites for chemical modification. Besides these distinct features, GQDs acquire peroxidase (POD)-mimicking electro-catalytic activity, and hence, they can replace horseradish peroxidase (HRP)-based systems to conduct facile, quick, and inexpensive label-free immunoassays. The chief motive of this review article is to summarize and focus on the recent advances in GQD-based electrochemical immunosensors for the early and rapid detection of cancer, cardiovascular disorders, and pathogenic diseases. Moreover, the underlying principles of electrochemical immunosensing techniques are also highlighted. These GQD immunosensors are ubiquitous in biomedical diagnosis and conducive for miniaturization, encouraging low-cost disease diagnostics in developing nations using point-of-care testing (POCT) and similar allusive techniques.TU Berlin, Open-Access-Mittel - 201

Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

BACKGROUND: Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. METHODS: The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm(2 )for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining. RESULTS: Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. CONCLUSION: We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy

Carbon nanotube biosensors for detection of biomarkers in breast cancer cells.

Detection and profiling of circulating tumor cells (CTCs) is useful for cancer screening and for managing treatment of carcinoma patients. Label-free technologies aim to accomplish detection rapidly with small, simple micro and nano devices. Carbon nanotubes are favorable molecular sensors due to their unique properties. They have been widely investigated for immunosensing of cancer biomarkers as free proteins, but very little has been done to detect biomarkers in intact cells and much remains to be understood regarding the mechanism of their sensing. We have developed a simple carbon nanotube biosensor for epithelial cell adhesion molecule (EpCAM) for sensing EpCAM positive cells. Sensor fabrication steps involving minimal air exposure were employed which reduced random noise upon sample introduction to the device. Optimized sensors recognized specific interactions with EpCAM positive MCF-7 cells and did not recognize EpCAM negative MCF-10A cells, producing the same characteristic signal as for blank phosphate buffered saline samples (no interaction). A two sample t-test found that the specific and nonspecific signals were significantly different, p = 0.0235. Specific binding signals are attributed to the combined binding events and negative cell membrane potential

Field Effect Transistor Nanosensor for Breast Cancer Diagnostics

Silicon nanochannel field effect transistor (FET) biosensors are one of the most promising technologies in the development of highly sensitive and label-free analyte detection for cancer diagnostics. With their exceptional electrical properties and small dimensions, silicon nanochannels are ideally suited for extraordinarily high sensitivity. In fact, the high surface-to-volume ratios of these systems make single molecule detection possible. Further, FET biosensors offer the benefits of high speed, low cost, and high yield manufacturing, without sacrificing the sensitivity typical for traditional optical methods in diagnostics. Top down manufacturing methods leverage advantages in Complementary Metal Oxide Semiconductor (CMOS) technologies, making richly multiplexed sensor arrays a reality. Here, we discuss the fabrication and use of silicon nanochannel FET devices as biosensors for breast cancer diagnosis and monitoring

Advances in cancer therapy through the use of carbon nanotube-mediated targeted hyperthermia

Carbon nanotubes (CNTs) are emerging versatile tools in nanomedicine applications, particularly in the field of cancer targeting. Due to diverse surface chemistry and unique thermal properties, CNTs can act as strong optical absorbers in near infrared light where biological systems prove to be highly transparent. The process of laser-mediated ablation of cancer cells marked with biofunctionalized CNTs is frequently termed “nanophotothermolysis.” This paper illustrates the potential of engineered CNTs as laser-activated photothermal agents for the selective nanophotothermolysis of cancer cells