Staff directory Maria Soler Aznar

Maria Soler Aznar

Visiting Postdoctoral Researcher
CIBER
maria.soler(ELIMINAR)@icn2.cat
NanoBiosensors and Bioanalytical Applications

Publications

2021

  • 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: 2.286

    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).


2020

  • 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.


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.


2018

  • Nanophotonic biosensors: Expand live cell analysis

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

    [No abstract available]


  • Two-Dimensional Label-Free Affinity Analysis of Tumor-Specific CD8 T Cells with a Biomimetic Plasmonic Sensor

    Soler M., Li X., John-Herpin A., Schmidt J., Coukos G., Altug H. ACS Sensors; 3 (11): 2286 - 2295. 2018. 10.1021/acssensors.8b00523.

    The screening and analysis of T cells functional avidity for specific tumor-associated antigens is crucial for the development of personalized immunotherapies against cancer. The affinity and kinetics of a T cell receptor (TCR) binding to the peptide-major histocompatibility complex (pMHC), expressed on tumor or antigen-presenting cells, have shown major implications in T cell activation and effector functions. We introduce an innovative methodology for the two-dimensional affinity analysis of TCR-pMHC in a label-free configuration by employing a multiparametric Surface Plasmon Resonance biosensor (MP-SPR) functionalized with artificial cell membranes. The biomimetic scaffold created with planar lipid bilayers is able to efficiently capture the specific and intact tumor-specific T cells and monitor the formation of the immunological synapse in situ. We have achieved excellent limits of detection for in-flow cell capturing, up to 2 orders of magnitude below the current state-of-the-art for plasmonic sensing. We demonstrate the accuracy and selectivity of our sensor for the analysis of CD8+ T cells bioengineered with TCR of incremental affinities specific for the HLA-A0201/NY-ESO-I157-165 pMHC complex. The study confirmed the significance of providing a biomimetic microenvironment, compared to the traditional molecular analysis, and showed fine agreement with previous results employing flow cytometry. Our methodology is reliable and versatile; thus, it can be applied to more sophisticated photonic and nanoplasmonic technologies for the screening of multiple cell types and boost the development of novel treatments for cancer. © 2018 American Chemical Society.


2017

  • 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.


2016

  • 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.


2015

  • 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.