Staff directory Maria Carmen Estévez Alberola

Publications

2024

  • Validation of a plasmonic-based serology biosensor for veterinary diagnosis of COVID-19 in domestic animals

    Giarola, JF; Soler, M; Estevez, MC; Tarasova, A; Le Poder, S; Wasniewski, M; Decaro, N; Lechuga, LM Talanta; 271: 125685. 2024. 10.1016/j.talanta.2024.125685.


2022

  • Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

    Calvo-Lozano O., Sierra M., Soler M., Estévez M.C., Chiscano-Camón L., Ruiz-Sanmartin A., Ruiz-Rodriguez J.C., Ferrer R., González-López J.J., Esperalba J., Fernández-Naval C., Bueno L., López-Aladid R., Torres A., Fernández-Barat L., Attoumani S., Charrel R., Coutard B., Lechuga L.M. Analytical Chemistry; 94 (2): 975 - 984. 2022. 10.1021/acs.analchem.1c03850. IF: 6.986

    Serological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL–1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment. © 2021 The Authors. Published by American Chemical Society


  • Novel Sensing Algorithm for Linear Read-Out of Bimodal Waveguide Interferometric Biosensors

    Bassols-Cornudella B., Ramirez-Priego P., Soler M., Estevez M.-C., Luis-Ravelo H.J.D., Cardenosa-Rubio M., Lechuga L.M. Journal of Lightwave Technology; 40 (1): 237 - 244. 2022. 10.1109/JLT.2021.3118103. IF: 4.142

    Biosensors employing photonics integrated circuits, and specifically those that rely on interferometric evanescent wave working principles, have outstanding performances due to the extreme sensitivity exhibited in one-step and direct assay, without the need of amplification. Within the interferometric configurations, the Bimodal Waveguide (BiMW) interferometric sensor stands out due to its demonstrated sensitivity for real-life applications and the simplicity of its design. To overcome the ambiguities that arise from the periodic nature of interferometric read-outs, a new all-optical modulation and the subsequent trigonometry-based algorithm have been proposed and applied to the BiMW biosensor. This new algorithm has been successfully employed for the selective identification and quantification of the external Spike (S) protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our biosensing results from this simple, quick, and user-friendly method demonstrate high sensitivity and specificity and pave the way towards a point-of-care device for general use. © 1983-2012 IEEE.


  • One-Step and Real-Time Detection of microRNA-21 i n Human Samples for Lung Cancer Biosensing Diagnosis

    Calvo-Lozano, O; Garcia-Aparicio, P; Raduly, LZ; Estevez, MC; Berindan-Neagoe, I; Ferracin, M; Lechuga, LM Analytical Chemistry; 94 (42): 14659 - 14665. 2022. 10.1021/acs.analchem.2c02895. IF: 8.008


  • Rapid and direct quantification of the SARS-CoV-2 virus with an ultrasensitive nanobody-based photonic nanosensor

    Ruiz-Vega, Gisela; Soler, Maria; Estevez, MCarmen; Ramirez-Priego, Patricia; Pazos, Martalu D.; Noriega, María A.; Margolles, Yago; Francés-Gómez, Clara; Geller, Ron; Matusali, Giulia; Colavita, Francesca; di Caro, Antonino; Casasnovas, José M.; Fernández, Luis Angel; Lechuga, Laura M. Sensors &Amp; Diagnostics; 2022. 10.1039/d2sd00082b.


2021

  • Real-time monitoring of fenitrothion in water samples using a silicon nanophotonic biosensor

    Ramirez-Priego P., Estévez M.-C., Díaz-Luisravelo H.J., Manclús J.J., Montoya Á., Lechuga L.M. Analytica Chimica Acta; 1152 (338276) 2021. 10.1016/j.aca.2021.338276. IF: 6.558

    Due to the large quantities of pesticides extensively used and their impact on the environment and human health, a prompt and reliable sensing technique could constitute an excellent tool for in-situ monitoring. With this aim, we have applied a highly sensitive photonic biosensor based on a bimodal waveguide interferometer (BiMW) for the rapid, label-free, and specific quantification of fenitrothion (FN) directly in tap water samples. After an optimization protocol, the biosensor achieved a limit of detection (LOD) of 0.29 ng mL−1 (1.05 nM) and a half-maximal inhibitory concentration (IC50) of 1.71 ng mL−1 (6.09 nM) using a competitive immunoassay and employing diluted tap water. Moreover, the biosensor was successfully employed to determine FN concentration in blind tap water samples obtaining excellent recovery percentages with a time-to-result of only 20 min without any sample pre-treatment. The features of the biosensor suggest its potential application for real time, fast and sensitive screening of FN in water samples as an analytical tool for the monitoring of the water quality. © 2021 Elsevier B.V.


2020

  • A compact SPR biosensor device for the rapid and efficient monitoring of gluten-free diet directly in human urine

    Peláez E.C., Estevez M.-C., Domínguez R., Sousa C., Cebolla A., Lechuga L.M. Analytical and Bioanalytical Chemistry; 2020. 10.1007/s00216-020-02616-6. IF: 3.637

    Celiac disease (CD) is a chronic autoimmune disorder induced in genetically susceptible individuals by the ingestion of gluten from wheat, rye, barley, or certain varieties of oats. A careful diet follow-up is necessary to avoid health complications associated with long-term gluten intake by the celiac patients. Small peptides (GIP, gluten immunogenic peptides) derived from gluten digestion, which are excreted in the urine and feces, have emerged as promising biomarkers to monitor gluten intake. We have implemented a simple and sensitive label-free point-of-care (POC) device based on surface plasmon resonance for the direct detection of these biomarkers in urine. The assay employs specific monoclonal antibodies and has been optimized for the detection of the 33-mer α2-gliadin, known as the main immunogenic peptide of wheat gluten, and for the detection of GIP. Direct detection in undiluted urine has been accomplished by using biosensing chips containing a robust and stable biorecognition layer, obtained after carefully optimizing the biofunctionalization protocol. Excellent limits of detection have been reached (1.6–4.0 ng mL−1 using mAb G12 and A1, respectively), which ensures the detection of gluten peptides even when the gluten intake is around the maximum tolerable amount in the digestive tract (< 50 mg) for celiac individuals. No sample pretreatment, extraction, or dilution is required, and the analysis takes less than 15 min. The assays have excellent reproducibility‚ as demonstrated by measuring spiked urine samples containing the same target concentration using different biofunctionalized chips prepared and stored at different periods of time (i.e., CV% of 3.58% and 11.30%, for G12- and A1-based assays, respectively). The assay has been validated with real samples. These features pave the way towards an end-user easy-to-handle biosensor device for the rapid monitoring of gluten-free diet (GFD) and follow-up of the health status in celiac patients. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.


  • Detection and Quantification of HspX Antigen in Sputum Samples Using Plasmonic Biosensing: Toward a Real Point-of-Care (POC) for Tuberculosis Diagnosis

    Peláez E.C., Estevez M.C., Mongui A., Menéndez M.-C., Toro C., Herrera-Sandoval O.L., Robledo J., García M.J., Portillo P.D., Lechuga L.M. ACS infectious diseases; 6 (5): 1110 - 1120. 2020. 10.1021/acsinfecdis.9b00502. IF: 4.614

    Advancements that occurred during the last years in the diagnosis of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis infection, have prompted increased survival rates of patients. However, limitations related to the inefficiency of an early detection still remain; some techniques and laboratory methods do not have enough specificity and most instruments are expensive and require handling by trained staff. In order to contribute to a prompt and effective diagnosis of tuberculosis, we report the development of a portable, user-friendly, and low-cost biosensor device for its early detection. By using a label-free surface plasmon resonance (SPR) biosensor, we have established a direct immunoassay for the direct detection and quantification of the heat shock protein X (HspX) of Mtb, a well-established biomarker of this pathogen, directly in pretreated sputum samples. The method relies on highly specific monoclonal antibodies that are previously immobilized on the plasmonic sensor surface. This technology allows for the direct detection of the biomarker without amplification steps, showing a limit of detection (LOD) of 0.63 ng mL-1 and a limit of quantification (LOQ) of 2.12 ng mL-1. The direct analysis in pretreated sputum shows significant differences in the HspX concentration in patients with tuberculosis (with concentration levels in the order of 116-175 ng mL-1) compared with non-tuberculosis infected patients (values below the LOQ of the assay).


  • How Nanophotonic Label-Free Biosensors Can Contribute to Rapid and Massive Diagnostics of Respiratory Virus Infections: COVID-19 Case

    Soler M., Estevez M.C., Cardenosa-Rubio M., Astua A., Lechuga L.M. ACS Sensors; 5 (9): 2663 - 2678. 2020. 10.1021/acssensors.0c01180. IF: 7.333

    The global sanitary crisis caused by the emergence of the respiratory virus SARS-CoV-2 and the COVID-19 outbreak has revealed the urgent need for rapid, accurate, and affordable diagnostic tests to broadly and massively monitor the population in order to properly manage and control the spread of the pandemic. Current diagnostic techniques essentially rely on polymerase chain reaction (PCR) tests, which provide the required sensitivity and specificity. However, its relatively long time-to-result, including sample transport to a specialized laboratory, delays massive detection. Rapid lateral flow tests (both antigen and serological tests) are a remarkable alternative for rapid point-of-care diagnostics, but they exhibit critical limitations as they do not always achieve the required sensitivity for reliable diagnostics and surveillance. Next-generation diagnostic tools capable of overcoming all the above limitations are in demand, and optical biosensors are an excellent option to surpass such critical issues. Label-free nanophotonic biosensors offer high sensitivity and operational robustness with an enormous potential for integration in compact autonomous devices to be delivered out-of-the-lab at the point-of-care (POC). Taking the current COVID-19 pandemic as a critical case scenario, we provide an overview of the diagnostic techniques for respiratory viruses and analyze how nanophotonic biosensors can contribute to improving such diagnostics. We review the ongoing published work using this biosensor technology for intact virus detection, nucleic acid detection or serological tests, and the key factors for bringing nanophotonic POC biosensors to accurate and effective COVID-19 diagnosis on the short term. Copyright © 2020 American Chemical Society.


  • Label-free detection of nosocomial bacteria using a nanophotonic interferometric biosensor

    Maldonado J., Estévez M.-C., Fernández-Gavela A., González-López J.J., González-Guerrero A.B., Lechuga L.M. Analyst; 145 (2): 497 - 506. 2020. 10.1039/c9an01485c. IF: 3.978

    Nosocomial infections are a major concern at the worldwide level. Early and accurate identification of nosocomial pathogens is crucial to provide timely and adequate treatment. A prompt response also prevents the progression of the infection to life-threatening conditions, such as septicemia or generalized bloodstream infection. We have implemented two highly sensitive methodologies using an ultrasensitive photonic biosensor based on a bimodal waveguide interferometer (BiMW) for the fast detection of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), two of the most prevalent bacteria associated with nosocomial infections. For that, we have developed a biofunctionalization strategy based on the use of a PEGylated silane (silane-PEG-COOH) which provides a highly resistant and bacteria-repelling surface, which is crucial to specifically detect each bacterium. Two different biosensor assays have been set under standard buffer conditions: One based on a specific direct immunoassay employing polyclonal antibodies for the detection of P. aeruginosa and another one employing aptamers for the direct detection of MRSA. The biosensor immunoassay for P. aeruginosa is fast (it only takes 12 min) and specific and has experimentally detected concentrations down to 800 cfu mL-1 (cfu: Colony forming unit). The second one relies on the use of an aptamer that specifically detects penicillin-binding protein 2a (PBP2a), a protein only expressed in the MRSA mutant, providing a photonic biosensor with the ability to identify the resistant pathogen MRSA and differentiate it from methicillin-susceptible S. aureus (MSSA). Direct, label-free, and selective detection of whole MRSA bacteria has been achieved, making possible the direct detection of also 800 cfu mL-1. According to the signal-to-noise (S/N) ratio of the device, a theoretical limit of detection (LOD) of around 49 and 29 cfu mL-1 was estimated for P. aeruginosa and MRSA, respectively. Both results obtained under standard conditions reveal the great potential this interferometric biosensor device has as a versatile and specific tool for bacterial detection and quantification, providing a rapid method for the identification of nosocomial pathogens within the clinical requirements of sensitivity for the diagnosis of infections. © 2020 The Royal Society of Chemistry.


  • Nanophotonic biosensors: Driving personalized medicine

    Soler M., Calvo-Lozano O., Carmen Estevez M., Lechuga L.M. Optics and Photonics News; 31 (4): 25 - 31. 2020. 10.1364/OPN.31.4.000024. IF: 0.000

    [No abstract available]


  • One-Step Immobilization of Antibodies and DNA on Gold Sensor Surfaces via a Poly-Adenine Oligonucleotide Approach

    Huertas C.S., Soler M., Estevez M.-C., Lechuga L.M. Analytical Chemistry; 92 (18): 12596 - 12604. 2020. 10.1021/acs.analchem.0c02619. IF: 6.785

    Label-free plasmonic biosensors have demonstrated promising capabilities as analytical tools for the detection of virtually any type of biomarker. They are presented as good candidates for precision diagnostics since they offer highly sensitive, cost-effective solutions that can be used in any clinical or laboratory setting without the need for specialized trainees. However, different surface functionalization protocols are required, depending on the nature of the biorecognition element, limiting their capabilities for integrated multi-biomarker detection. Here, we present a simple, yet efficient, one-step immobilization approach that is common for both DNA probes and antibodies. Our immobilization approach relies on the incorporation of poly-adenine (polyA) blocks in both nucleic acid probes and antibodies. PolyA sequences have a remarkable affinity for gold surfaces and can specifically interact with sufficient strength to generate stable, dense, and highly ordered monolayers. We have demonstrated excellent performance of our universal functionalization method, showing limits of detection and quantification in the pM-nM range. Moreover, it was able to reduce up to 50% of the background signal from undiluted serum samples compared to conventional methods, demonstrating the immense potential of this strategy for the direct analysis of human biofluids, essential for rapid point-of-care diagnostics. The polyA-based immobilization approach is a promising alternative for the generation of multiplexed biosensors that can detect both protein and nucleic acid biomarkers for multiparametric diagnostic assays. Copyright © 2020 American Chemical Society.


  • Optical nanogap antennas as plasmonic biosensors for the detection of miRNA biomarkers

    Portela A., Calvo-Lozano O., Estevez M., Medina Escuela A., Lechuga L.M. Journal of Materials Chemistry B; 8 (19): 4310 - 4317. 2020. 10.1039/d0tb00307g. IF: 5.344

    Nanoplasmonic biosensors based on nanogap antenna structures usually demand complex and expensive fabrication processes in order to achieve a good performance and sensitive detection. We here report the fabrication of large-area nanoplasmonic sensor chips based on nanogap antennas by employing a customized, simple and low-cost colloidal lithography process. By precisely controlling the angle for tilted e-beam metal evaporation, an elliptical mask is produced, which defines the total length of the dipole antenna nanostructures while assuring that the plasmonic response is oriented in the same direction along the sensor chip. Large-area sensor chips of nanogap antennas formed by pairs of gold nanodisks separated by gaps with an average size of 11.6 ± 4.7 nm are obtained. The optical characterization of the nanogap antenna structures in an attenuated total reflection (ATR) configuration shows a bulk refractive index sensitivity of 422 nm per RIU, which is in agreement with FDTD numerical simulations. The biosensing potential of the cm2-sized nanostructured plasmonic sensor chips has been evaluated for the detection of miRNA-210, a relevant biomarker for lung cancer diagnosis, through a DNA/miRNA hybridization assay. A limit of detection (LOD) of 0.78 nM (5.1 ng mL-1) was achieved with no need of further amplification steps, demonstrating the high sensitivity of these plasmonic nanogap antennas for the direct and label-free detection of low molecular weight biomolecules such as miRNAs. © The Royal Society of Chemistry 2020.


2019

  • Early sepsis diagnosis via protein and miRNA biomarkers using a novel point-of-care photonic biosensor

    Fabri-Faja N., Calvo-Lozano O., Dey P., Terborg R.A., Estevez M.-C., Belushkin A., Yesilköy F., Duempelmann L., Altug H., Pruneri V., Lechuga L.M. Analytica Chimica Acta; 1077: 232 - 242. 2019. 10.1016/j.aca.2019.05.038. IF: 5.256

    Sepsis is a condition characterized by a severe stage of blood-infection often leading to tissue damage, organ failure and finally death. Fast diagnosis and identification of the sepsis stage (sepsis, severe sepsis or septic shock) is critical for the patient's evolution and could help in defining the most adequate treatment in order to reduce its mortality. The combined detection of several biomarkers in a timely, specific and simultaneous way could ensure a more accurate diagnosis. We have designed a new optical point-of-care (POC) device based on a phase-sensitive interferometric biosensor with a label-free microarray configuration for potential high-throughput evaluation of specific sepsis biomarkers. The sensor chip, which relies on the use of metallic nanostructures, provides versatility in terms of biofunctionalization, allowing the efficient immobilization of different kind of receptors such as antibodies or oligonucleotides. We have focused on two structurally different types of biomarkers: proteins, including C-reactive protein (CRP) and Interleukin 6 (IL6), and miRNAs, using miRNA-16 as an example. Limits of Detection (LoD) of 18 μg mL−1, 88 μg mL−1 and 1 μM (6 μg mL−1) have been respectively obtained for CRP, IL6 and miRNA-16 in individual assays, with high accuracy and reproducibility. The multiplexing capabilities have also been assessed with the simultaneous analysis of both protein biomarkers. © 2019 Elsevier B.V.


  • Label-free Bacteria Quantification in Blood Plasma by a Bioprinted Microarray Based Interferometric Point-of-Care Device

    Dey P., Fabri-Faja N., Calvo-Lozano O., Terborg R.A., Belushkin A., Yesilkoy F., Fàbrega A., Ruiz-Rodriguez J.C., Ferrer R., González-López J.J., Estévez M.C., Altug H., Pruneri V., Lechuga L.M. ACS Sensors; 4 (1): 52 - 60. 2019. 10.1021/acssensors.8b00789. IF: 6.944

    Existing clinical methods for bacteria detection lack speed, sensitivity, and, importantly, point-of-care (PoC) applicability. Thus, finding ways to push the sensitivity of clinical PoC biosensing technologies is crucial. Here we report a portable PoC device based on lens-free interferometric microscopy (LIM). The device employs high performance nanoplasmonics and custom bioprinted microarrays and is capable of direct label-free bacteria (E. coli) quantification. With only one-step sample handling we offer a sample-to-data turnaround time of 40 min. Our technology features detection sensitivity of a single bacterial cell both in buffer and in diluted blood plasma and is intrinsically limited by the number of cells present in the detection volume. When employed in a hospital setting, the device has enabled accurate categorization of sepsis patients (infectious SIRS) from control groups (healthy individuals and noninfectious SIRS patients) without false positives/negatives. User-friendly on-site bacterial clinical diagnosis can thus become a reality. © 2018 American Chemical Society.


  • Label-Free Nanoplasmonic Biosensing of Cancer Biomarkers for Clinical Diagnosis

    Portela A., Peláez E.C., Calvo-Lozano O., Estévez M.C., Lechuga L.M. Methods in Molecular Biology; 2027: 115 - 140. 2019. 10.1007/978-1-4939-9616-2_10.

    Biosensing of cancer biomarkers enabling early diagnosis of cancer constitutes an essential tool for clinical intervention and application of novel therapies against cancer disease. Optical biosensor instruments as point-of-care (POC) devices and operating under label-free scheme have demonstrated to provide fast, simple, and high-sensitivity assays even at home care environment. Nanoplasmonic biosensors are thought to be a powerful tool for detection of complex analytes of relevant clinical applications. Using high-throughput fabrication techniques, large surface patterned with gold nanodisk structures is obtained showing surface sensitivities with limit of detection (LOD) in the order of picomolar concentration range. Here, we describe two major assay methodologies used for detection of lung and colorectal cancer, respectively. Particularly, we have selected a complementary hybridization DNA/RNA assay for the assessment of two miRNAs (miRNA-210 and miRNA-205) for detection of lung cancer. However, for colorectal cancer we present the detection of four tumor-associated antigen (TAA) biomarkers (MAPKAPK3, PIM-1, STK4, and GTF2B) as possible TAA targets for autoantibody production. Strategies for detecting these biomarkers in real samples such as serum are also presented, demonstrating the capabilities of these assays to be transferred to real clinical settings. © Springer Science+Business Media, LLC, part of Springer Nature 2019.


  • Label-free, scalable and point-of-care imaging platform for rapid analysis of biomarker

    L. Duempelmann, R. A. Terborg, J. Pello, I. Mannelli, F. Yesilkoy, A. A. Belushkin, Y. Jahani, N. Fabri-Faja, P. Dey, O. Calvo-Lozano, M. -. Estevez, A. Fàbrega, J. J. González-López, L. M. Lechuga, H. Altug, and V. Pruneri SPIE Proceedings (Optical Society of America, 2019); Clinical and Preclinical Optical Diagnostics II, V 2019. 10.1117/12.2525878.

    We propose a disruptive point-of-care (PoC) imaging platform based on lens-free interference phase-contrast imaging for rapid detection of biomarker such as for sepsis and potentially other diseases (e.g. cancer). It enables simultaneous analysis of potentially up to 10,000 functionalized microarray spots with different biomarkers with fast time-to-results (few minutes) and by consuming a small sample volume (~10 µL). The high sensitivity allows direct measurements of the biomarker binding without the use of fluorescent labels (e.g. ELISA) or microbial culture methods. In addition, ad-hoc plasmonic nano-structuring is utilized to significantly improve the sensitivity for biomarker detection (optical path difference ~Å) to concentration levels relevant for disease diagnosis. The proposed technology incorporates a portable and low-cost lens-free imaging reader made of consumer electronic components, plasmonic microarrays with distinct functionalization, and user-friendly software based on a novel phase-shifting interferometry method for topography and refractive index analysis. Due to its compactness and cost-efficiency, we foresee a great potential for PoC applications, especially for the rapid detection of infectious diseases or life-threatening conditions, e.g. sepsis, but also for clinical trials of drugs and food control.


2018

  • Gold/silver/gold trilayer films on nanostructured polycarbonate substrates for direct and label-free nanoplasmonic biosensing

    López-Muñoz G.A., Estévez M.-C., Vázquez-García M., Berenguel-Alonso M., Alonso-Chamarro J., Homs-Corbera A., Lechuga L.M. Journal of Biophotonics; 11 (8, e201800043) 2018. 10.1002/jbio.201800043. IF: 3.768

    Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commercial Blu-ray optical discs as nanoslits-based flexible polymer substrates. A thin gold film was used as an adhesion and nucleation layer to improve the chemical stability and reduce the surface roughness of the overlying silver film, without increasing ohmic plasmon losses. The structures were physically and optically characterized and compared with nanostructures of single gold layer. Ultrasmooth and chemically stable trilayer nanostructures with a surface roughness <0.5 nm were obtained following a simple and reproducible fabrication process. They showed a figure of merit (FOM) value up to 69.2 RIU−1 which is significantly higher (more than 95%) than the gold monolayer counterpart. Their potential for biosensing was demonstrated by employing the trilayer sensor for the direct and refractometric (label-free) detection of C-reactive protein (CRP) biomarker in undiluted urine achieving a Limit of Detection (LOD) in the pM order. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


  • Nanoplasmonic biosensor device for the monitoring of acenocoumarol therapeutic drug in plasma

    Peláez E.C., Estevez M.-C., Portela A., Salvador J.-P., Marco M.-P., Lechuga L.M. Biosensors and Bioelectronics; 119: 149 - 155. 2018. 10.1016/j.bios.2018.08.011. IF: 8.173

    Acenocoumarol (Sintrom®) is an oral anticoagulant prescribed for the treatment of a variety of thromboembolic disorders such as atrial fibrillation and thrombosis or embolism. It inhibits fibrin production preventing clot formation. Acenocoumarol has a narrow therapeutic range, and its effects depend on several factors, such as body weight, age, metabolism, diet, certain medical conditions or the intake of additional drugs, among others. A higher dose may result in the risk of bleeding, while if it is too low, the risk of blood clot can increase. Complementary tools that allow the therapeutic drug monitoring (TDM) of acenocoumarol plasmatic levels from the starting of the treatment would be of paramount importance to personalize the treatment. Point-of-care (POC) devices can offer an added value in facilitating on-site monitoring (i.e. hospitals, primary care doctor or even by the patient itself) and can aid in dosage management. With this aim, we have developed a compact and simple nanoplasmonic sensing device based on gold nanodisks for the rapid monitoring of acenocoumarol, using highly specific polyclonal antibodies produced against this drug. A specific and reproducible label free indirect competitive assay has been developed and the viability of performing the evaluation directly in plasma diluted 1:1 has been demonstrated. A limit of detection (LOD) of only 0.77 ± 0.69 nM, an IC50 of 48.2 ± 5.12 nM and a dynamic range between 3.38 ± 1.33 nM and 1154 ± 437 nM were achieved, which easily fit within the drug plasma levels of acenocoumarol, making this approach a highly attractive option for its decentralized monitoring in human plasma. © 2018 Elsevier B.V.