Staff directory Maria Soler Aznar



  • Biomimetic nanoplasmonic sensor for rapid evaluation of neutralizing SARS-CoV-2 monoclonal antibodies as antiviral therapy

    Batool, R; Soler, M; Colavita, F; Fabeni, L; Matusali, G; Lechuga, LM Biosensors & Bioelectronics; 226: 115137. 2023. 10.1016/j.bios.2023.115137. IF: 12.600


  • Biochemistry strategies for label-free optical sensor biofunctionalization: advances towards real applicability

    Soler M., Lechuga L.M. Analytical and Bioanalytical Chemistry; 414 (18): 5071 - 5085. 2022. 10.1007/s00216-021-03751-4. IF: 4.157

    Label-free biosensors, and especially those based on optical transducers like plasmonic or silicon photonic systems, have positioned themselves as potential alternatives for rapid and highly sensitive clinical diagnostics, on-site environmental monitoring, and for quality control in foods or other industrial applications, among others. However, most of the biosensor technology has not yet been transferred and implemented in commercial products. Among the several causes behind that, a major challenge is the lack of standardized protocols for sensor biofunctionalization. In this review, we summarize the most common methodologies for sensor surface chemical modification and bioreceptor immobilization, discussing their advantages and limitations in terms of analytical sensitivity and selectivity, reproducibility, and versatility. Special focus is placed on the suggestions of innovative strategies towards antifouling and biomimetic functional coatings to boost the applicability and reliability of optical biosensors in clinics and biomedicine. Finally, a brief overview of research directions in the area of device integration, automation, and multiplexing will give a glimpse of the future perspectives for label-free optical biosensors. © 2021, The Author(s).

  • Integrated optical bimodal waveguide biosensors: Principles and applications

    Torrijos-Morán L., Lisboa B.D., Soler M., Lechuga L.M., García-Rupérez J. Results in Optics; 9 (100285) 2022. 10.1016/

    Integrated optical biosensors have become one of the most compelling technologies for the achievement of highly sensitive, multianalyte, portable and easy to use point-of-care (POC) devices with tremendous impact in healthcare and environmental protection, among other application fields. In this context, bimodal waveguide (BiMW) interferometers have emerged over the last years as a powerful biosensor technology providing the benefits of extreme sensitivity under a label-free scheme, reliability and robustness within a highly compact footprint that can be integrated and multiplexed in lab-on-a-chip (LOC) platforms. In this review, we provide an overview of the state-of-the-art about integrated optical BiMW biosensors from the theoretical fundamentals to their practical implementation. Furthermore, we explore recent advances such as novel designs, integration in specific LOC systems and its application in real biosensing scenarios. Final remarks and perspectives on the potential impact of these biosensor interferometric structures are also provided, as well as some limitations that must be addressed in next steps. © 2022 The Author(s)

  • 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.

  • 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.


  • Design and characterization of high-affinity synthetic peptides as bioreceptors for diagnosis of cutaneous leishmaniasis

    Prada Y.A., Soler M., Guzmán F., Castillo J.J., Lechuga L.M., Mejía-Ospino E. Analytical and Bioanalytical Chemistry; 413 (17): 4545 - 4555. 2021. 10.1007/s00216-021-03424-2. IF: 4.157

    Cutaneous leishmaniasis (CL) is one of the illnesses caused by Leishmania parasite infection, which can be asymptomatic or severe according to the infecting Leishmania strain. CL is commonly diagnosed by directly detecting the parasites or their DNA in tissue samples. New diagnostic methodologies target specific proteins (biomarkers) secreted by the parasite during the infection process. However, specific bioreceptors for the in vivo or in vitro detection of these novel biomarkers are rather limited in terms of sensitivity and specificity. For this reason, we here introduce three novel peptides as bioreceptors for the highly sensitive and selective identification of acid phosphatase (sAP) and proteophosphoglycan (PPG), which have a crucial role in leishmaniasis infection. These high-affinity peptides have been designed from the conservative domains of the lectin family, holding the ability to interact with the biological target and produce the same effect than the original protein. The synthetic peptides have been characterized and the affinity and kinetic constants for their interaction with the targets (sAP and PPG) have been determined by a surface plasmon resonance biosensor. Values obtained for KD are in the nanomolar range, which is comparable to high-affinity antibodies, with the additional advantage of a high biochemical stability and simpler production. Pep2854 exhibited a high affinity for sAP (KD = 1.48 nM) while Pep2856 had a good affinity for PPG (KD 1.76 nM). This study evidences that these peptidomimetics represent a novel alternative tool to the use of high molecular weight proteins for biorecognition in the diagnostic test and biosensor devices for CL. Graphical abstract: [Figure not available: see fulltext.]. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

  • Nanophotonic biosensors for point-of-care COVID-19 diagnostics and coronavirus surveillance

    Ruiz-Vega G., Soler M., Lechuga L.M. JPhys Photonics; 3 (1, 011002) 2021. 10.1088/2515-7647/abd4ee. IF: 0.000

    The COVID-19 pandemic has revealed the need of novel diagnostic technologies for rapid and accurate virus detection. In the European CONVAT project, a point-of-care nanophotonic biosensor is being developed for the direct, fast and specific identification of severe acute respiratory syndrome coronavirus 2 from both human patient samples and animal reservoirs. The technology will provide a quantitative detection of the viral load and it can be implemented in decentralized settings to improve the early diagnosis and clinical management of patients as well as coronavirus environmental monitoring to prevent future outbreaks. © 2021 The Author(s). Published by IOP Publishing Ltd

  • Principles, technologies, and applications of plasmonic biosensors

    Soler M., Lechuga L.M. Journal of Applied Physics; 129 (11, 111102) 2021. 10.1063/5.0042811. IF: 2.546

    Plasmonic materials and phenomena have been widely studied and applied in multiple fields for a long time. One of the most promising applications is in the engineering of biosensor devices, offering label-free and real-time analysis of biomolecular interactions with excellent performances. In this tutorial, we provide a pedagogical review of the working principles of plasmonic biosensors, main fabrication methods, instrumentation, and general guidelines for their development. Special focus is placed on the biosensor performance characterization and assessment, as well as on the sensor surface biofunctionalization. In the end, we discuss the common procedure to develop and validate biosensors for relevant biomedical and environmental purposes and future perspectives in terms of boosting capabilities and sensor integration in point-of-care platforms. © 2021 Author(s).


  • Engineering photonics solutions for COVID-19

    Soler M., Scholtz A., Zeto R., Armani A.M. APL Photonics; 5 (9, 090901) 2020. 10.1063/5.0021270. IF: 4.864

    As the impact of COVID-19 on society became apparent, the engineering and scientific community recognized the need for innovative solutions. Two potential roadmaps emerged: Developing short-term solutions to address the immediate needs of the healthcare communities and developing mid/long-term solutions to eliminate the over-arching threat. However, in a truly global effort, researchers from all backgrounds came together in tackling this challenge. Short-term efforts have focused on re-purposing existing technologies and leveraging additive manufacturing techniques to address shortages in personal protective equipment and disinfection. More basic research efforts with mid-term and long-term impact have emphasized developing novel diagnostics and accelerating vaccines. As a foundational technology, photonics has contributed directly and indirectly to all efforts. This perspective will provide an overview of the critical role that the photonics field has played in efforts to combat the immediate COVID-19 pandemic as well as how the photonics community could anticipate contributing to future pandemics of this nature. © 2020 Author(s).

  • 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.

  • 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.


  • Boosting cancer immunotherapy with optical biosensor nanotechnologies

    M. Soler and L. M. Lechuga European Medical Journal; 4 (4): 124 - 132. 2019. .

  • Label-free plasmonic biosensors for point-of-care diagnostics: a review

    Soler M., Huertas C.S., Lechuga L.M. Expert Review of Molecular Diagnostics; 19 (1): 71 - 81. 2019. 10.1080/14737159.2019.1554435. IF: 3.099

    Introduction: Optical biosensors, particularly those based on nanoplasmonics technology, have emerged in recent decades as a potential solution for disease diagnostics and therapy follow-up at the point-of-care (POC). These biosensor platforms could overcome some of the challenges faced in conventional diagnosis techniques offering label-free assays with immediate results and employing small and user-friendly devices. Areas covered: In this review, we will provide a critical overview of the recent advances in the development of nanoplasmonic biosensors for the POC diagnostics. We focus on those systems with demonstrated capabilities for integration in portable platforms, highlighting some of the most relevant diagnostics applications targeting proteins, nucleic acids, and cells as disease biomarkers. Expert commentary: Despite the attractive features of label-free nanoplasmonic sensors in terms of miniaturization and analytical robustness, the route toward an effective clinical implementation involves the integration of fully automated microfluidic systems for sample processing and analysis, and the optimization of surface biofunctionalization procedures. Additionally, the development of multiplexed sensors for high-throughput analysis and including specific neoantigens and novel biomarkers in detection panels will provide the means for delivering a powerful analytical technology for an accurate and improved medical diagnosis. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

  • Site-Specific mRNA Cleavage for Selective and Quantitative Profiling of Alternative Splicing with Label-Free Optical Biosensors

    Huertas C.S., Bonnal S., Soler M., Escuela A.M., Valcárcel J., Lechuga L.M. Analytical Chemistry; 91 (23): 15138 - 15146. 2019. 10.1021/acs.analchem.9b03898. IF: 6.350

    Alternative splicing of mRNA precursors is a key process in gene regulation, contributing to the diversity of proteomes by the alternative selection of exonic sequences. Alterations in this mechanism are associated with most cancers, enhancing their proliferation and survival, and can be employed as cancer biomarkers. Label-free optical biosensors are ideal tools for the highly sensitive and label-free analysis of nucleic acids. However, their application for alternative splicing analysis has been hampered due to the formation of complex and intricate long-range base-pairing interactions which make the direct detection in mRNA isoforms difficult. To solve this bottleneck, we introduce a methodology for the generation of length-controlled RNA fragments from purified total RNA, which can be easily detected by the biosensor. The methodology seizes RNase H enzyme activity to degrade the upstream and downstream RNA segments flanking the target sequence upon hybridization to specific DNA oligos. It allows the fast and direct monitoring of Fas gene alternative splicing in real time, employing a surface plasmon resonance biosensor. We demonstrate the selective and specific detection of mRNA fragments in the pM-nM concentration range, reducing quantification errors and showing 81% accuracy when compared to RT-qPCR. The site-specific cleavage outperformed random RNA hydrolysis by increasing the detection accuracy by 20%, making this methodology particularly appropriate for label-free quantification of alternative splicing events in complex samples. Copyright © 2019 American Chemical Society.


  • Nanophotonic biosensors: Expand live cell analysis

    Li X., Soler M., Yesilkoy F., Altug H. Biophotonics International; 25 (7): 28 - 33. 2018. .

    [No abstract available]


  • Recent advances in nanoplasmonic biosensors: Applications and lab-on-a-chip integration

    Lopez G.A., Estevez M.-C., Soler M., Lechuga L.M. Nanophotonics; 6 (1): 123 - 136. 2017. 10.1515/nanoph-2016-0101. IF: 4.492

    Motivated by the recent progress in the nanofabrication field and the increasing demand for cost-effective, portable, and easy-to-use point-of-care platforms, localized surface plasmon resonance (LSPR) biosensors have been subjected to a great scientific interest in the last few years. The progress observed in the research of this nanoplasmonic technology is remarkable not only from a nanostructure fabrication point of view but also in the complete development and integration of operative devices and their application. The potential benefits that LSPR biosensors can offer, such as sensor miniaturization, multiplexing opportunities, and enhanced performances, have quickly positioned them as an interesting candidate in the design of lab-on-a-chip (LOC) optical biosensor platforms. This review covers specifically the most significant achievements that occurred in recent years towards the integration of this technology in compact devices, with views of obtaining LOC devices. We also discuss the most relevant examples of the use of the nanoplasmonic biosensors for real bioanalytical and clinical applications from assay development and validation to the identification of the implications, requirements, and challenges to be surpassed to achieve fully operative devices. © 2016, Laura M. Lechuga et al., published by De Gruyter.


  • Label-free nanoplasmonic sensing of tumor-associate autoantibodies for early diagnosis of colorectal cancer

    Soler M., Estevez M.-C., Villar-Vazquez R., Casal J.I., Lechuga L.M. Analytica Chimica Acta; 930: 31 - 38. 2016. 10.1016/j.aca.2016.04.059. IF: 4.712

    Colorectal cancer is treatable and curable when detected at early stages. However there is a lack of less invasive and more specific screening and diagnosis methods which would facilitate its prompt identification. Blood circulating autoantibodies which are immediately produced by the immune system at tumor appearance have become valuable biomarkers for preclinical diagnosis of cancer. In this work, we present the rapid and label-free detection of colorectal cancer autoantibodies directly in blood serum or plasma using a recently developed nanoplasmonic biosensor. Our nanoplasmonic device offers sensitive and real-time quantification of autoantibodies with excellent selectivity and reproducibility, achieving limits of detection around 1 nM (150-160 ng mL-1). A preliminary evaluation of clinical samples of colorectal cancer patients has shown good correlation with ELISA. These results demonstrate the reliability of the nanobiosensor strategy and pave the way towards the achievement of a sensitive diagnostic tool for early detection of colorectal cancer. © 2016 Elsevier B.V.

  • Label-free SPR detection of gluten peptides in urine for non-invasive celiac disease follow-up

    Soler M., Estevez M.-C., Moreno M.D.L., Cebolla A., Lechuga L.M. Biosensors and Bioelectronics; 79: 158 - 164. 2016. 10.1016/j.bios.2015.11.097. IF: 7.476

    Motivated by the necessity of new and efficient methods for dietary gluten control of celiac patients, we have developed a simple and highly sensitive SPR biosensor for the detection of gluten peptides in urine. The sensing methodology enables rapid and label-free quantification of the gluten immunogenic peptides (GIP) by using G12 mAb. The overall performance of the biosensor has been in-depth optimized and evaluated in terms of sensitivity, selectivity and reproducibility, reaching a limit of detection of 0.33ngmL-1. Besides, the robustness and stability of the methodology permit the continuous use of the biosensor for more than 100 cycles with excellent repeatability. Special efforts have been focused on preventing and minimizing possible interferences coming from urine matrix enabling a direct analysis in this fluid without requiring extraction or purification procedures. Our SPR biosensor has proven to detect and identify gluten consumption by evaluating urine samples from healthy and celiac individuals with different dietary gluten conditions. This novel biosensor methodology represents a novel approach to quantify the digested gluten peptides in human urine with outstanding sensitivity in a rapid and non-invasive manner. Our technique should be considered as a promising opportunity to develop Point-of-Care (POC) devices for an efficient, simple and accurate gluten free diet (GFD) monitoring as well as therapy follow-up of celiac disease patients. © 2015 Elsevier B.V.


  • Highly sensitive dendrimer-based nanoplasmonic biosensor for drug allergy diagnosis

    Soler M., Mesa-Antunez P., Estevez M.-C., Ruiz-Sanchez A.J., Otte M.A., Sepulveda B., Collado D., Mayorga C., Torres M.J., Perez-Inestrosa E., Lechuga L.M. Biosensors and Bioelectronics; 66: 115 - 123. 2015. 10.1016/j.bios.2014.10.081. IF: 6.409

    A label-free biosensing strategy for amoxicillin (AX) allergy diagnosis based on the combination of novel dendrimer-based conjugates and a recently developed nanoplasmonic sensor technology is reported. Gold nanodisks were functionalized with a custom-designed thiol-ending-polyamido-based dendron (d-BAPAD) peripherally decorated with amoxicilloyl (AXO) groups (d-BAPAD-AXO) in order to detect specific IgE generated in patient's serum against this antibiotic during an allergy outbreak. This innovative strategy, which follows a simple one-step immobilization procedure, shows exceptional results in terms of sensitivity and robustness, leading to a highly-reproducible and long-term stable surface which allows achieving extremely low limits of detection. Moreover, the viability of this biosensor approach to analyze human biological samples has been demonstrated by directly analyzing and quantifying specific anti-AX antibodies in patient's serum without any sample pretreatment. An excellent limit of detection (LoD) of 0.6. ng/mL (i.e. 0.25. kU/L) has been achieved in the evaluation of clinical samples evidencing the potential of our nanoplasmonic biosensor as an advanced diagnostic tool to quickly identify allergic patients. The results have been compared and validated with a conventional clinical immunofluorescence assay (ImmunoCAP test), confirming an excellent correlation between both techniques. The combination of a novel compact nanoplasmonic platform and a dendrimer-based strategy provides a highly sensitive label free biosensor approach with over two times better detectability than conventional SPR. Both the biosensor device and the carrier structure hold great potential in clinical diagnosis for biomarker analysis in whole serum samples and other human biological samples. © 2014 Elsevier B.V.