Parallel optical read-out of micromechanical pillars applied to prostate specific membrane antigen detection
Micro and nanomechanical resonators represent a promising platform for proteins label-free detection because of their extreme sensitivity, fast response and low cost. Micro-pillars are columnar resonators that can be easily arranged in dense arrays of several thousand sensors in a squared mm. To exp...
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Veröffentlicht in: | Biosensors & bioelectronics 2015-10, Vol.72, p.393-399 |
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creator | Tardivo, Martina Toffoli, Valeria Fracasso, Giulio Borin, Daniele Dal Zilio, Simone Colusso, Andrea Carrato, Sergio Scoles, Giacinto Meneghetti, Moreno Colombatti, Marco Lazzarino, Marco |
description | Micro and nanomechanical resonators represent a promising platform for proteins label-free detection because of their extreme sensitivity, fast response and low cost. Micro-pillars are columnar resonators that can be easily arranged in dense arrays of several thousand sensors in a squared mm. To exploit such a large density, however, a method for tracking independently micropillars resonance frequency is required. Here we present a detection method based on CCD imaging and software image analysis, which can measure the resonance frequency of tens of pillars in parallel. Acquiring simultaneously the frequency shift of up to 40 sensors and applying a proper statistical analysis, we were able to overcome the variability of the single measures improving the device sensitivity at low analyte concentration range.
As a proof of concept, this method has been tested for the detection of a tumor marker, the Prostate Specific Membrane Antigen (PSMA). Pillars have been functionalized with an antibody against PSMA. The tumor marker (PSMA) has been detected in a range of concentrations between 300pM and 100nM, in buffer and in diluted bovine serum. The sensitivity of our method was limited only by the affinity constant of the antigen–antibody recognition. Moreover, this detection technique demonstrated to be effective in the 1–6nM range, which is the window of PSMA concentration of clinical interest.
•High density micromechanical vertical sensors arrays are used for biomolecular detection.•A novel approach to monitor the resonance frequency of tens of pillars in parallel is presented.•Device sensitivity is improved over single pillar resonator by averaging signals coming from a multitude of sensors.•Label free detection, faster adsorption kinetics, higher sensitivity, small analytes volumes are advantages coming from pillar technology.•Prostate Specific Membrane Antigen is detected in the concentration range of clinical interest. |
doi_str_mv | 10.1016/j.bios.2015.05.026 |
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As a proof of concept, this method has been tested for the detection of a tumor marker, the Prostate Specific Membrane Antigen (PSMA). Pillars have been functionalized with an antibody against PSMA. The tumor marker (PSMA) has been detected in a range of concentrations between 300pM and 100nM, in buffer and in diluted bovine serum. The sensitivity of our method was limited only by the affinity constant of the antigen–antibody recognition. Moreover, this detection technique demonstrated to be effective in the 1–6nM range, which is the window of PSMA concentration of clinical interest.
•High density micromechanical vertical sensors arrays are used for biomolecular detection.•A novel approach to monitor the resonance frequency of tens of pillars in parallel is presented.•Device sensitivity is improved over single pillar resonator by averaging signals coming from a multitude of sensors.•Label free detection, faster adsorption kinetics, higher sensitivity, small analytes volumes are advantages coming from pillar technology.•Prostate Specific Membrane Antigen is detected in the concentration range of clinical interest.</description><identifier>ISSN: 0956-5663</identifier><identifier>EISSN: 1873-4235</identifier><identifier>DOI: 10.1016/j.bios.2015.05.026</identifier><identifier>PMID: 26025134</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Antibodies, Immobilized - chemistry ; Antigens ; Biomarkers, Tumor - blood ; Biosensing Techniques - instrumentation ; Density ; Equipment Design ; Humans ; Limit of Detection ; Male ; Markers ; Micro-Electrical-Mechanical Systems - instrumentation ; Micromechanical sensors ; Parallel optical read-out detection ; Pillars ; Prostate ; Prostate - pathology ; Prostate Specific Membrane Antigen ; Prostate-Specific Antigen - blood ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - diagnosis ; Resonators ; Sensors ; Tumors</subject><ispartof>Biosensors & bioelectronics, 2015-10, Vol.72, p.393-399</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-cdd280e1ab14c8d1675c9f8cb0f88ee11e83ad7867ae99ec8a75c93619d5f36e3</citedby><cites>FETCH-LOGICAL-c532t-cdd280e1ab14c8d1675c9f8cb0f88ee11e83ad7867ae99ec8a75c93619d5f36e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0956566315301214$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26025134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tardivo, Martina</creatorcontrib><creatorcontrib>Toffoli, Valeria</creatorcontrib><creatorcontrib>Fracasso, Giulio</creatorcontrib><creatorcontrib>Borin, Daniele</creatorcontrib><creatorcontrib>Dal Zilio, Simone</creatorcontrib><creatorcontrib>Colusso, Andrea</creatorcontrib><creatorcontrib>Carrato, Sergio</creatorcontrib><creatorcontrib>Scoles, Giacinto</creatorcontrib><creatorcontrib>Meneghetti, Moreno</creatorcontrib><creatorcontrib>Colombatti, Marco</creatorcontrib><creatorcontrib>Lazzarino, Marco</creatorcontrib><title>Parallel optical read-out of micromechanical pillars applied to prostate specific membrane antigen detection</title><title>Biosensors & bioelectronics</title><addtitle>Biosens Bioelectron</addtitle><description>Micro and nanomechanical resonators represent a promising platform for proteins label-free detection because of their extreme sensitivity, fast response and low cost. Micro-pillars are columnar resonators that can be easily arranged in dense arrays of several thousand sensors in a squared mm. To exploit such a large density, however, a method for tracking independently micropillars resonance frequency is required. Here we present a detection method based on CCD imaging and software image analysis, which can measure the resonance frequency of tens of pillars in parallel. Acquiring simultaneously the frequency shift of up to 40 sensors and applying a proper statistical analysis, we were able to overcome the variability of the single measures improving the device sensitivity at low analyte concentration range.
As a proof of concept, this method has been tested for the detection of a tumor marker, the Prostate Specific Membrane Antigen (PSMA). Pillars have been functionalized with an antibody against PSMA. The tumor marker (PSMA) has been detected in a range of concentrations between 300pM and 100nM, in buffer and in diluted bovine serum. The sensitivity of our method was limited only by the affinity constant of the antigen–antibody recognition. Moreover, this detection technique demonstrated to be effective in the 1–6nM range, which is the window of PSMA concentration of clinical interest.
•High density micromechanical vertical sensors arrays are used for biomolecular detection.•A novel approach to monitor the resonance frequency of tens of pillars in parallel is presented.•Device sensitivity is improved over single pillar resonator by averaging signals coming from a multitude of sensors.•Label free detection, faster adsorption kinetics, higher sensitivity, small analytes volumes are advantages coming from pillar technology.•Prostate Specific Membrane Antigen is detected in the concentration range of clinical interest.</description><subject>Antibodies, Immobilized - chemistry</subject><subject>Antigens</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biosensing Techniques - instrumentation</subject><subject>Density</subject><subject>Equipment Design</subject><subject>Humans</subject><subject>Limit of Detection</subject><subject>Male</subject><subject>Markers</subject><subject>Micro-Electrical-Mechanical Systems - instrumentation</subject><subject>Micromechanical sensors</subject><subject>Parallel optical read-out detection</subject><subject>Pillars</subject><subject>Prostate</subject><subject>Prostate - pathology</subject><subject>Prostate Specific Membrane Antigen</subject><subject>Prostate-Specific Antigen - blood</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Resonators</subject><subject>Sensors</subject><subject>Tumors</subject><issn>0956-5663</issn><issn>1873-4235</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUuLFDEUhYM4OO3oH3AhWbqpNo_OC9zIMA9hYGah65BKbmmaVKVM0sL8e9P2jEsRLtzF_c7hcg5C7yjZUkLlx_12jLluGaFiS_ow-QJtqFZ82DEuXqINMUIOQkp-jl7XuieEKGrIK3TOJGGC8t0GpQdXXEqQcF5b9C7hAi4M-dBwnvAcfckz-B9u-XNbY0quVOzWNUUIuGW8llyba4DrCj5O0eMZ5rG4BbBbWvwOCw7QwLeYlzfobHKpwtunfYG-XV99vbwd7u5vvlx-vhu84KwNPgSmCVA30p3XgUolvJm0H8mkNQCloLkLSkvlwBjw2h0BLqkJYuIS-AX6cPLtz_08QG12jtVD_32BfKiWKkWYEYro_0C5MJQbpjrKTmjPpNYCk11LnF15tJTYYyF2b4-F2GMhlvRhsoveP_kfxhnCX8lzAx34dAKgB_IrQrHVR1g8hFh6ajbk-C__31_5nlA</recordid><startdate>20151015</startdate><enddate>20151015</enddate><creator>Tardivo, Martina</creator><creator>Toffoli, Valeria</creator><creator>Fracasso, Giulio</creator><creator>Borin, Daniele</creator><creator>Dal Zilio, Simone</creator><creator>Colusso, Andrea</creator><creator>Carrato, Sergio</creator><creator>Scoles, Giacinto</creator><creator>Meneghetti, Moreno</creator><creator>Colombatti, Marco</creator><creator>Lazzarino, Marco</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SP</scope><scope>7U5</scope><scope>L7M</scope></search><sort><creationdate>20151015</creationdate><title>Parallel optical read-out of micromechanical pillars applied to prostate specific membrane antigen detection</title><author>Tardivo, Martina ; Toffoli, Valeria ; Fracasso, Giulio ; Borin, Daniele ; Dal Zilio, Simone ; Colusso, Andrea ; Carrato, Sergio ; Scoles, Giacinto ; Meneghetti, Moreno ; Colombatti, Marco ; Lazzarino, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-cdd280e1ab14c8d1675c9f8cb0f88ee11e83ad7867ae99ec8a75c93619d5f36e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antibodies, Immobilized - chemistry</topic><topic>Antigens</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biosensing Techniques - instrumentation</topic><topic>Density</topic><topic>Equipment Design</topic><topic>Humans</topic><topic>Limit of Detection</topic><topic>Male</topic><topic>Markers</topic><topic>Micro-Electrical-Mechanical Systems - instrumentation</topic><topic>Micromechanical sensors</topic><topic>Parallel optical read-out detection</topic><topic>Pillars</topic><topic>Prostate</topic><topic>Prostate - pathology</topic><topic>Prostate Specific Membrane Antigen</topic><topic>Prostate-Specific Antigen - blood</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Resonators</topic><topic>Sensors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tardivo, Martina</creatorcontrib><creatorcontrib>Toffoli, Valeria</creatorcontrib><creatorcontrib>Fracasso, Giulio</creatorcontrib><creatorcontrib>Borin, Daniele</creatorcontrib><creatorcontrib>Dal Zilio, Simone</creatorcontrib><creatorcontrib>Colusso, Andrea</creatorcontrib><creatorcontrib>Carrato, Sergio</creatorcontrib><creatorcontrib>Scoles, Giacinto</creatorcontrib><creatorcontrib>Meneghetti, Moreno</creatorcontrib><creatorcontrib>Colombatti, Marco</creatorcontrib><creatorcontrib>Lazzarino, Marco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biosensors & bioelectronics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tardivo, Martina</au><au>Toffoli, Valeria</au><au>Fracasso, Giulio</au><au>Borin, Daniele</au><au>Dal Zilio, Simone</au><au>Colusso, Andrea</au><au>Carrato, Sergio</au><au>Scoles, Giacinto</au><au>Meneghetti, Moreno</au><au>Colombatti, Marco</au><au>Lazzarino, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Parallel optical read-out of micromechanical pillars applied to prostate specific membrane antigen detection</atitle><jtitle>Biosensors & bioelectronics</jtitle><addtitle>Biosens Bioelectron</addtitle><date>2015-10-15</date><risdate>2015</risdate><volume>72</volume><spage>393</spage><epage>399</epage><pages>393-399</pages><issn>0956-5663</issn><eissn>1873-4235</eissn><abstract>Micro and nanomechanical resonators represent a promising platform for proteins label-free detection because of their extreme sensitivity, fast response and low cost. Micro-pillars are columnar resonators that can be easily arranged in dense arrays of several thousand sensors in a squared mm. To exploit such a large density, however, a method for tracking independently micropillars resonance frequency is required. Here we present a detection method based on CCD imaging and software image analysis, which can measure the resonance frequency of tens of pillars in parallel. Acquiring simultaneously the frequency shift of up to 40 sensors and applying a proper statistical analysis, we were able to overcome the variability of the single measures improving the device sensitivity at low analyte concentration range.
As a proof of concept, this method has been tested for the detection of a tumor marker, the Prostate Specific Membrane Antigen (PSMA). Pillars have been functionalized with an antibody against PSMA. The tumor marker (PSMA) has been detected in a range of concentrations between 300pM and 100nM, in buffer and in diluted bovine serum. The sensitivity of our method was limited only by the affinity constant of the antigen–antibody recognition. Moreover, this detection technique demonstrated to be effective in the 1–6nM range, which is the window of PSMA concentration of clinical interest.
•High density micromechanical vertical sensors arrays are used for biomolecular detection.•A novel approach to monitor the resonance frequency of tens of pillars in parallel is presented.•Device sensitivity is improved over single pillar resonator by averaging signals coming from a multitude of sensors.•Label free detection, faster adsorption kinetics, higher sensitivity, small analytes volumes are advantages coming from pillar technology.•Prostate Specific Membrane Antigen is detected in the concentration range of clinical interest.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>26025134</pmid><doi>10.1016/j.bios.2015.05.026</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies, Immobilized - chemistry Antigens Biomarkers, Tumor - blood Biosensing Techniques - instrumentation Density Equipment Design Humans Limit of Detection Male Markers Micro-Electrical-Mechanical Systems - instrumentation Micromechanical sensors Parallel optical read-out detection Pillars Prostate Prostate - pathology Prostate Specific Membrane Antigen Prostate-Specific Antigen - blood Prostatic Neoplasms - blood Prostatic Neoplasms - diagnosis Resonators Sensors Tumors |
title | Parallel optical read-out of micromechanical pillars applied to prostate specific membrane antigen detection |
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