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  • Disposable Sensors in Diagnostics, Food, and Environmental Monitoring
    Publication . Dincer, Can; Bruch, Richard; Costa-Rama, Estefanía; Fernández‐Abedul, Maria Teresa; Merkoçi, Arben; Manz, Andreas; Urban, Gerald Anton; Güder, Firat
    Disposable sensors are low-cost and easy-to-use sensing devices intended for short-term or rapid single-point measurements. The growing demand for fast, accessible, and reliable information in a vastly connected world makes disposable sensors increasingly important. The areas of application for such devices are numerous, ranging from pharmaceutical, agricultural, environmental, forensic, and food sciences to wearables and clinical diagnostics, especially in resource-limited settings. The capabilities of disposable sensors can extend beyond measuring traditional physical quantities (for example, temperature or pressure); they can provide critical chemical and biological information (chemo- and biosensors) that can be digitized and made available to users and centralized/decentralized facilities for data storage, remotely. These features could pave the way for new classes of low-cost systems for health, food, and environmental monitoring that can democratize sensing across the globe. Here, a brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis. Finally, views on how the field of disposable sensing devices will continue its evolution are discussed, including the future trends, challenges, and opportunities.
  • Competitive electrochemical immunosensor for the detection of unfolded p53 protein in blood as biomarker for Alzheimer’s disease
    Publication . Amor-Gutiérrez, Olaya; Costa Rama, Estefanía; Arce-Varas, Noemi; Martínez-Rodríguez, Carmen; Novelli, Antonello; Fernández-Sánchez, María Teresa; Costa-García, Agustín
    Alzheimer's disease is one of the most common causes of dementia nowadays, and its prevalence increases over time. Because of this and the difficulty of its diagnosis, accurate methods for the analysis of specific biomarkers for an early diagnosis of this disease are much needed. Recently, the levels of unfolded isoform of the multifunctional protein p53 in plasma have been proved to increase selectively in Alzheimer's Disease patients in comparison with healthy subjects, thus entering the list of biomarkers that can be used for the diagnosis of this illness. We present here the development of an electrochemical immunosensor based on nanostructured screen-printed carbon electrodes for the quantification of unfolded p53 in plasma samples. The sensor shows a suitable linear range (from 2 to 50 nM) for its application in real blood samples and a very low limit of detection (0.05 nM). The concentration of unfolded p53 has been accurately detected in plasma of elderly people in healthy conditions, subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD) subjects, obtaining results with no significant differences to those provided by an ELISA assay. These results support the possibility of measuring unfolded p53 levels with a cheap, simple and miniaturized device with a promising future for point-of-care applications in the early diagnosis of Alzheimer's dementia.
  • Diamine oxidase-modified screen-printed electrode for the redox-mediated determination of histamine
    Publication . Torre, Ricarda; Costa Rama, Estefanía; Nouws, Henri; Delerue-Matos, Cristina
    Histamine is an important biogenic amine because of its role in immune responses and the regulation of physiological functions. It is also used as a food freshness indicator, so its maximum concentration in fish is legally regulated. Although several robust and sensitive methods for histamine detection are already available, it continues to be a challenge to develop simple and portable devices that allow rapid histamine screening at any point of the fish production chain. Thus, in this work, a simple, miniaturized and low-cost sensor for histamine analysis was developed. The construction of the sensor only takes 30 min and consists of the immobilization of the enzyme diamine oxidase on the surface of a screen-printed carbon electrode by cross-linking. The quantification of histamine was achieved by chronoamperometry (+ 0.2V,120 s) using hexacyanoferrate (III) as a redox mediator. This selective sensor provided a low limit of detection (0.97 mg L−1) and accurate and precise results and was successfully applied to the analysis of spiked tuna and mackerel extracts,obtaining recovery values of 99–100%. Moreover, the sensor shows good stability, maintaining 87.7% of its initial signalafter 35 days.
  • Disposable electrochemical immunosensor for analysis of cystatin C, a CKD biomarker
    Publication . LOPES, Paula; Costa Rama, Estefanía; Beirão, Idalina; Nouws, Henri; Santos-Silva, Alice; Delerue-Matos, Cristina
    Specific monitoring of cystatin C (CysC) levels in biological fluids is critical for diagnosis, treatment and mechanistic understanding of a spectrum of diseases, particularly chronic kidney disease (CKD). Despite evidences that CysC correlates with the high risk and/or progression of CKD, its use in clinical practice is still scarce. In this context, we report the development of a simple and sensitive immunosensor for the detection of CysC. The biosensor combines the technology of cost-effective screen-printed electrodes with the high specificity of a sandwich immunoassay. Optimized conditions showed that the sensor operates in a linear range between 10 and 100 ng mL-1, with a detection limit and a sensitivity of 6.0 ng mL-1 and 6.4 ± 0.3 μA ng mL-1 cm-2, respectively. Moreover, the sensor provided precise results (RSD ≤ 6.2%) and the quantification of CysC in CKD serum samples revealed to be in agreement with the values obtained by a particle-enhanced nephelometric immunoassay. In this light, the proposed immunosensor qualifies for clinical application, constituting a step forward in the development of fast, sensitive and cost-effective diagnostic tools that can improve the current medical care settings of CKD patients.
  • Voltammetric immunosensor for the simultaneous analysis of the breast cancer biomarkers CA 15-3 and HER2-ECD
    Publication . Marques, Raquel C.B.; Costa Rama, Estefanía; Viswanathan, Subramanian; Nouws, Henri; Costa-García, Agustín; Delerue-Matos, Cristina; González-García, M. Begoña
    Cancer Antigen 15-3 (CA 15-3) and the extracellular domain of the human epidermal growth factor receptor 2 (HER2-ECD) are independent breast cancer biomarkers. The combination of their profiles (presence and concentration) could provide an important contribution to diagnostics and patient follow-up. Therefore, a disposable electrochemical immunosensor for the simultaneous detection of CA 15-3 and HER2-ECD was developed in this work. The immunosensor was constructed on a customized dual screen-printed carbon electrode. The carbon working electrodes' surfaces were first modified with in situ electrodeposited gold nanoparticles and then individually coated with either a monoclonal anti-human CA 15-3 or a monoclonal anti-human HER2-ECD antibody. After incubation with the biomarkers and monoclonal biotin-labelled detection antibodies, the antigen-antibody interactions were detected by linear sweep voltammetric analysis of enzymatically (alkaline phosphatase) generated metallic silver. The immunosensor’s limits of detection for the selected biomarkers were 5.0 U mL−1 for CA 15-3 and 2.9 ng mL−1 for HER2-ECD. These values could allow the use of the sensor in the non-invasive control of these biomarkers in breast cancer patients.
  • Amperometric enzyme sensor for the rapid determination of histamine
    Publication . Torre, Ricarda; Costa Rama, Estefanía; LOPES, Paula; Nouws, Henri; Delerue-Matos, Cristina
    The concentration of histamine, a biogenic amine, in fish is considered a fish spoilage indicator. Therefore, the development of a rapid-response and portable tool that allows its on-site analysis is very interesting since the consumption of high amounts of histamine causes scombroid poisoning. Thus, in this work a simple enzymatic sensor for the determination of histamine, based on a screen-printed carbon electrode and the enzyme diamine oxidase, was developed. The enzyme was immobilized on the electrode surface through a simple cross-linking procedure employing glutaraldehyde and bovine serum albumin. Chronoamperometry was used as the detection technique; the sensor showed a short response time (60 s, -0.3 V) and the measurements were performed by only using 40 μL of sample solution. The sensor provides an useful linear range (between 1 and 75 mg L-1 in fish extract), excellent reproducibility (RSD = 2.6%) and is reusable for up to 7 measurements. The feasibility of the sensor was tested performing histamine analysis in fish extracts achieving recovery values of 103%.