The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review

Background: Electrical impedance technology has been well established for the last 20 years. Recently research has begun to emerge into its potential uses in the detection and diagnosis of pre-malignant and malignant conditions. The aim of this study was to systematically review the clinical application of electrical impedance technology in the detection of malignant neoplasms. Methods: A search of Embase Classic, Embase and Medline databases was conducted from 1980 to 22/02/2018 to identify studies reporting on the use of bioimpedance technology in the detection of pre-malignant and malignant conditions. The ability to distinguish between tissue types was defined as the primary endpoint, and other points of interest were also reported. Results: 731 articles were identified, of which 51 reported sufficient data for analysis. These studies covered 16 different cancer subtypes in a total of 7035 patients. As the studies took various formats, a qualitative analysis of each cancer subtype’s data was undertaken. All the studies were able to show differences in electrical impedance and/or related metrics between malignant and normal tissue. Conclusions: Electrical impedance technology provides a novel method for the detection of malignant tissue, with large studies of cervical, prostate, skin and breast cancers showing encouraging results. Whilst these studies provide promising insights into the potential of this technology as an adjunct in screening, diagnosis and intra-operative margin assessment, customised development as well as multi-centre clinical trials need to be conducted before it can be reliably employed in the clinical detection of malignant tissue

The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review

Background: Electrical impedance technology has been well established for the last 20 years. Recently research has begun to emerge into its potential uses in the detection and diagnosis of pre-malignant and malignant conditions. The aim of this study was to systematically review the clinical application of electrical impedance technology in the detection of malignant neoplasms. Methods: A search of Embase Classic, Embase and Medline databases was conducted from 1980 to 22/02/2018 to identify studies reporting on the use of bioimpedance technology in the detection of pre-malignant and malignant conditions. The ability to distinguish between tissue types was defined as the primary endpoint, and other points of interest were also reported. Results: 731 articles were identified, of which 51 reported sufficient data for analysis. These studies covered 16 different cancer subtypes in a total of 7035 patients. As the studies took various formats, a qualitative analysis of each cancer subtype’s data was undertaken. All the studies were able to show differences in electrical impedance and/or related metrics between malignant and normal tissue. Conclusions: Electrical impedance technology provides a novel method for the detection of malignant tissue, with large studies of cervical, prostate, skin and breast cancers showing encouraging results. Whilst these studies provide promising insights into the potential of this technology as an adjunct in screening, diagnosis and intra-operative margin assessment, customised development as well as multi-centre clinical trials need to be conducted before it can be reliably employed in the clinical detection of malignant tissue

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

Fibrin association at hybrid biointerfaces made of clot-binding peptides and polythiophene

The properties as biointerfaces of electroactive conducting polymer-peptide biocomposites formed by poly(3,4-ethylenedioxythiophene) (PEDOT) and CREKA or CR(NMe)EKA peptide sequences (where Glu has been replaced by N-methyl-Glu in the latter) have been compared. CREKA is a linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, while CR(NMe)EKA is an engineer to improve such properties by altering peptide-fibrin interactions. Differences between PEDOT-CREKA and PEDOT-CR(NMe)EKA reflect dissemblance in the organization of the peptides into the polymeric matrix. Both peptides affect fibrinogen thrombin-catalyzed polymerization causing the immediate formation of fibrin, whereas in the absence of thrombin this phenomenon is only observed for CR(NMe)EKA. Consistently, the fibrin-adsorption capacity is higher for PEDOT-CR(NMe)EKA than for PEDOT-CREKA, even though in both cases adsorbed fibrin exhibits round-like morphologies rather than the characteristic fibrous structure. PEDOT-peptide films coated with fibrin are selective in terms of cell adhesion, promoting the attachment of metastatic cells with respect to normal cells.Peer ReviewedPostprint (author's final draft

Nerve localization techniques for peripheral nerve block and possible future directions

Ultrasound guidance is now a standard nerve localization technique for peripheral nerve block (PNB). Ultrasonography allows simultaneous visualization of the target nerve, needle, local anesthetic injectate and surrounding anatomical structures. Accurate deposition of local anesthetic next to the nerve is essential to the success of the nerve block procedure. Unfortunately, due to limitations in the visibility of both needle tip and nerve surface, the precise relationship between needle tip and target nerve is unknown at the moment of injection. Importantly, nerve injury may result both from an inappropriately placed needle tip and inappropriately placed local anesthetic. The relationship between the block needle tip and target nerve is of paramount importance to the safe conduct of peripheral nerve block. This review summarizes the evolution of nerve localization in regional anesthesia, characterizes a problem faced by clinicians in performing ultrasound guided nerve block and explores the potential technological solutions to this problem

Development of a low-cost graphene-based impedance biosensor

PhD ThesisThe current applicability and accuracy of point-of-care devices is limited, with the need of future technologies to simultaneously target multiple analytes in complex human samples. Graphene’s discovery has provided a valuable opportunity towards the development of high performance biosensors. The quality and surface properties of graphene devices are critical for biosensing applications with a preferred low contact resistance interface between metal and graphene. However, each graphene production method currently results in inconsistent properties, quality and defects thus limiting its application towards mass production. Also, post-production processing, patterning and conventional lithography-based contact deposition negatively impact graphene properties due to chemical contamination. The work of this thesis focuses on the development of fully-functional, label-free graphene-based biosensors and a proof-of-concept was established for the detection of prostate specific antigen (PSA) in aqueous solution using graphene platforms. Extensive work was carried out to characterize different graphene family nanomaterials in order to understand their potential for biosensing applications. Two graphene materials, obtained via a laser reduction process, were selected for further investigations: reduced graphene oxide (rGO) and laser induced graphene from polyimide (LIG). Electrically conductive, porous and chemically active to an extent, these materials offer the advantage of simultaneous production and patterning as capacitive biosensing structures, i.e. interdigitated electrode arrays (IDE). Aiming to enhance the sensitivity of these biosensors, a novel, radio-frequency (RF) detection method was investigated and compared with conventional electrochemical impedance spectroscopy (EIS) on a well-known biocompatible material: gold (standard). It was shown that the RF detection methods require careful design and testing setup, with conventional EIS performing better in the given conditions. The method was further used on rGO and LIG IDE devices for the electrochemical impedance detection of PSA to assess the feasibility of the graphene based materials as biosensors. The graphene-based materials were successfully functionalized via the available carboxylic groups, using the EDC-NHS chemistry. Despite the difficulty of producing reproducible graphene-based electrodes, highly required for biosensor development, extensive testing was carried out to understand their feasibility. The calibration curves obtained via successive PSA addition showed a moderate-to-high ii sensitivity of both rGO and LIG IDE. However, further adsorption and drift testing underlined some major limitations in the case of LIG, due to its complex morphology and large porosity. To enable low contact resistance to these biosensors, the electroless nickel coating process is shown to be compatible with various graphene-based materials. This was demonstrated by tuning the chemical nickel bath and method conditions for pristine graphene and rGO for nickel contacts deposition

Bioimpedance Sensing and Ablation Needles for Image-Guided Therapy

Sensing and ablation needles and catheter instruments combined with multimodal imaging, navigation and AI-assisted diagnosis have been increasingly utilised by interventional radiologists for image-guided therapy, emerging as an innovative tool for both diagnosis and treatment. This paper reviews the significant advancements in the field over the past decade, focusing on the development and refinement of both bioimpedance sensing needles and thermal ablation needles. Bioimpedance sensing needles differentiate pathological tissues by measuring impedance variations in biological tissues, offering a less invasive diagnostic approach. Thermal ablation needles, on the other hand, employ Radio Frequency (RF) techniques or Electrolytic Ablation (EA) to effectively target and treat lesions. This review covers the evolution of these needles, including advancements in materials, novel sensor technologies, impedance analysis methods, ablation catheter powering techniques, and needle design. It also provides insights into the needle structure, fabrication methods, and testing outcomes of these advanced sensing and ablation needles. Additionally, the paper presents an analysis of bioimpedance data across various pathological tissues and discusses innovative impedance analysis methodologies. The review concludes by presenting the current challenges in the field and discussing directions for future research, thereby providing an overview of the state-of-the-art in electronic technology for medical diagnosis and treatment needles

Impedance-Based Miniaturized Biosensor for Ultrasensitive and Fast Prostate-Specific Antigen Detection

This paper reports the successful fabrication of an impedance-based miniaturized biosensor and its application for ultrasensitive Prostate-Specific Antigen (PSA) detection in standard and real human plasma solution, spiked with different PSA concentrations. The sensor was fabricated using photolithographic techniques, while monoclonal antibodies specific to human PSA were used as primary capture antibodies. Electrochemical impedance spectroscopy (EIS) was employed as a detection technique. The sensor exhibited a detection limit of 1 pg/ml for PSA with minimal nonspecific binding (NSB). This detection limit is an order of magnitude lower than commercial PSA ELISA assays available on the market. The sensor can be easily modified into an array for the detection of other biomolecules of interest, enabling accurate, ultrasensitive, and inexpensive point-of-care sensing technologies

Label-free approaches for extracellular vesicle detection

Extracellular vesicles (EVs) represent pivotal mediators in cell-to-cell communication. They are lipid-membranous carriers of several biomolecules, which can be produced by almost all cells. In the current Era of precision medicine, EVs gained growing attention thanks to their potential in both biomarker discovery and nanotherapeutics applications. However, current technical limitations in isolating and/or detecting EVs restrain their standard use in clinics. This review explores all the state-of-the-art analytical technologies which are currently overcoming these issues. On one end, several innovative optical-, electrical- and spectroscopy-based detection methods represent advantageous label-free methodologies for faster EV detection. On the other end, microfluidics-based lab-on-a-chip tools support EV purification from low-concentrated samples. Altogether, these technologies will strengthen the routine application of EVs in clinics