title: Highly sensitive dendrimer-based nanoplasmonic biosensor for drug allergy diagnosis.
abstract: 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 0.6ng/mL (i.e. 0.25kU/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.
authors.affiliation: Nanobiosensors and Bioanalytical Applications Group, Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC and CIBER-BBN, 08193 Bellaterra (Barcelona), Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Soler
authors.affiliation: University of Malaga, IBIMA, Department of Organic Chemistry, 29071 Malaga, Spain; Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Mesa-Antunez
authors.affiliation: Nanobiosensors and Bioanalytical Applications Group, Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC and CIBER-BBN, 08193 Bellaterra (Barcelona), Spain. Electronic address: mcarmen.estevez@cin2.es.
authors.forename: M-Carmen
authors.initials: MC
authors.lastname: Estevez
authors.affiliation: University of Malaga, IBIMA, Department of Organic Chemistry, 29071 Malaga, Spain; Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain.
authors.forename: Antonio Jesus
authors.initials: AJ
authors.lastname: Ruiz-Sanchez
authors.affiliation: Nanobiosensors and Bioanalytical Applications Group, Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC and CIBER-BBN, 08193 Bellaterra (Barcelona), Spain.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Otte
authors.affiliation: Nanobiosensors and Bioanalytical Applications Group, Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC and CIBER-BBN, 08193 Bellaterra (Barcelona), Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: Sepulveda
authors.affiliation: University of Malaga, IBIMA, Department of Organic Chemistry, 29071 Malaga, Spain; Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Collado
authors.affiliation: Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain; Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, 29009 Malaga, Spain.
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.affiliation: Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain; Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, 29009 Malaga, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Torres
authors.affiliation: University of Malaga, IBIMA, Department of Organic Chemistry, 29071 Malaga, Spain; Andalusian Centre for Nanomedicine and Biotechnology-BIONAND, Parque Tecnologico de Andalucia, 29590 Malaga, Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Perez-Inestrosa
authors.affiliation: Nanobiosensors and Bioanalytical Applications Group, Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC and CIBER-BBN, 08193 Bellaterra (Barcelona), Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Lechuga
mesh_terms: D000658:Amoxicillin / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D050091:Dendrimers / Q000737:chemistry; D004342:Drug Hypersensitivity / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D004867:Equipment Design; D006046:Gold / Q000737:chemistry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D057230:Limit of Detection; D049329:Nanostructures / Q000737:chemistry; D009757:Nylons / Q000737:chemistry; D020349:Surface Plasmon Resonance / Q000295:instrumentation*
chemical_list: D000900:Anti-Bacterial Agents; D050091:Dendrimers; D009757:Nylons; D007073:Immunoglobulin E; D006046:Gold; D000658:Amoxicillin
keywords: Allergy diagnosis; Dendrimer; Gold nanodisks; IgE quantification; Label-free detection; Nanoplasmonic biosensor; Serum clinical sample