{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/157733"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/157733","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Towards a Single Bio-molecule Detector Based on CMOS Nanofluidic Platform","abstract":"Cytokines secretion is a core component of the function of many cell therapy products: It affects the tissue repair capacity of induced Pluripotent Stem Cells (iPSCs) and Mesenchymal Stem cells (MSCs) and the tumorigenicity of Chimeric Antigen Receptor (CAR) T-cell therapies. Ideally, we would be able to continuously monitor the secretome of these cell therapies as they are transformed and expanded in manufacturing.However, state-of-theart techniques for monitoring typically low concentrations of cytokines require either Mass Spectroscopy (MS) or immunoassays like Enzyme-linked Immunosorbent Assay (ELISA). We propose the use of CMOS technology to build a proteomic platform with a single biomolecule resolution. A prototype chip has been designed and fabricated using standard foundary process incorporating a new implementation of a Solid State Nanopore (SSN) of size 55nm×162nm×100nm (w×l×h) with nanofluidic access channels that bridge the buffer solution between the assay space in the packaging structure – a poly carbonate/Polydimethylsiloxane (PDMS) package- and the nanopore on the chip. A silicon Single Photon Avalanche Detectors (SPADs) was also implemented and placed near the nanochannels to utilize fluorescence labeling imaging techniques. In addition, a read-out amplifier that achieves a midband gain of 36.2 dB at a 3 dB bandwidth of 0.1-3.6 MHz is also implemented on the same silicon die, paving the way to superior performance compared to ionic current read-out systems used earlier for electrical biomolecule detection, thanks to low parasitics as a result of integration. The aforementioned modalities integrated on a single chip open the space for the use of CMOS platforms in the electrical and optical interrogation of biomolecules, opening a new horizon for near real-time biomarker assays. The following thesis builds on earlier work that was performed in [1][2] with the objective of expanding on different techniques to interface and characterize the performance of these modalities, especially after post-processing the chips with the aid of tools at MIT.nano. The thesis explores the further deployment of integrated SPAD in a Fluorescence Lifetime Imaging (FLIM) system to image fluorescence-labeled molecules, showcasing the capabilities of the CMOS nanofluidic platform to detect biomarkers such as cytokines.","abstract_html":"Cytokines secretion is a core component of the function of many cell therapy products: It affects the tissue repair capacity of induced Pluripotent Stem Cells (iPSCs) and Mesenchymal Stem cells (MSCs) and the tumorigenicity of Chimeric Antigen Receptor (CAR) T-cell therapies. Ideally, we would be able to continuously monitor the secretome of these cell therapies as they are transformed and expanded in manufacturing.However, state-of-theart techniques for monitoring typically low concentrations of cytokines require either Mass Spectroscopy (MS) or immunoassays like Enzyme-linked Immunosorbent Assay (ELISA). We propose the use of CMOS technology to build a proteomic platform with a single biomolecule resolution. A prototype chip has been designed and fabricated using standard foundary process incorporating a new implementation of a Solid State Nanopore (SSN) of size 55nm×162nm×100nm (w×l×h) with nanofluidic access channels that bridge the buffer solution between the assay space in the packaging structure – a poly carbonate/Polydimethylsiloxane (PDMS) package- and the nanopore on the chip. A silicon Single Photon Avalanche Detectors (SPADs) was also implemented and placed near the nanochannels to utilize fluorescence labeling imaging techniques. In addition, a read-out amplifier that achieves a midband gain of 36.2 dB at a 3 dB bandwidth of 0.1-3.6 MHz is also implemented on the same silicon die, paving the way to superior performance compared to ionic current read-out systems used earlier for electrical biomolecule detection, thanks to low parasitics as a result of integration. The aforementioned modalities integrated on a single chip open the space for the use of CMOS platforms in the electrical and optical interrogation of biomolecules, opening a new horizon for near real-time biomarker assays. The following thesis builds on earlier work that was performed in [1][2] with the objective of expanding on different techniques to interface and characterize the performance of these modalities, especially after post-processing the chips with the aid of tools at MIT.nano. The thesis explores the further deployment of integrated SPAD in a Fluorescence Lifetime Imaging (FLIM) system to image fluorescence-labeled molecules, showcasing the capabilities of the CMOS nanofluidic platform to detect biomarkers such as cytokines.","abstract_has_math":false,"creators":["Zikrallah, Ahmed S."],"institution":"Massachusetts Institute of Technology","degree_name":"Master","degree_level":null,"degree_discipline":null,"degree_department":"Program in Media Arts and Sciences (Massachusetts Institute of Technology)","school":null,"contributors":[],"advisors":["Ram, Rajeev J."],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-09","date_published":"2024-09","updated_at":"2026-07-22T22:21:13Z","subjects":[],"languages":[],"rights":["In Copyright - Educational Use Permitted","Copyright retained by author(s)"],"rights_urls":["https://rightsstatements.org/page/InC-EDU/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1721.1/157733","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ram, Rajeev J."]},{"key":"dc:contributor.department","label":"Department","values":["Program in Media Arts and Sciences (Massachusetts Institute of Technology)"]},{"key":"dc:creator","label":"Author","values":["Zikrallah, Ahmed S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-12-02T21:15:46Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-12-02T21:15:46Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-09"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master","Master of Science in Media Arts and Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright - Educational Use Permitted","Copyright retained by author(s)"]},{"key":"dc:rights.uri","label":"Rights URI","values":["https://rightsstatements.org/page/InC-EDU/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1721.1/157733"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Cytokines secretion is a core component of the function of many cell therapy products: It affects the tissue repair capacity of induced Pluripotent Stem Cells (iPSCs) and Mesenchymal Stem cells (MSCs) and the tumorigenicity of Chimeric Antigen Receptor (CAR) T-cell therapies. Ideally, we would be able to continuously monitor the secretome of these cell therapies as they are transformed and expanded in manufacturing.However, state-of-theart techniques for monitoring typically low concentrations of cytokines require either Mass Spectroscopy (MS) or immunoassays like Enzyme-linked Immunosorbent Assay (ELISA). We propose the use of CMOS technology to build a proteomic platform with a single biomolecule resolution. A prototype chip has been designed and fabricated using standard foundary process incorporating a new implementation of a Solid State Nanopore (SSN) of size 55nm×162nm×100nm (w×l×h) with nanofluidic access channels that bridge the buffer solution between the assay space in the packaging structure – a poly carbonate/Polydimethylsiloxane (PDMS) package- and the nanopore on the chip. A silicon Single Photon Avalanche Detectors (SPADs) was also implemented and placed near the nanochannels to utilize fluorescence labeling imaging techniques. In addition, a read-out amplifier that achieves a midband gain of 36.2 dB at a 3 dB bandwidth of 0.1-3.6 MHz is also implemented on the same silicon die, paving the way to superior performance compared to ionic current read-out systems used earlier for electrical biomolecule detection, thanks to low parasitics as a result of integration. The aforementioned modalities integrated on a single chip open the space for the use of CMOS platforms in the electrical and optical interrogation of biomolecules, opening a new horizon for near real-time biomarker assays. The following thesis builds on earlier work that was performed in [1][2] with the objective of expanding on different techniques to interface and characterize the performance of these modalities, especially after post-processing the chips with the aid of tools at MIT.nano. The thesis explores the further deployment of integrated SPAD in a Fluorescence Lifetime Imaging (FLIM) system to image fluorescence-labeled molecules, showcasing the capabilities of the CMOS nanofluidic platform to detect biomarkers such as cytokines."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["S.M."]},{"key":"dc:title","label":"Title","values":["Towards a Single Bio-molecule Detector Based on CMOS Nanofluidic Platform"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ram, Rajeev J."],"dc:contributor.department":["Program in Media Arts and Sciences (Massachusetts Institute of Technology)"],"dc:creator":["Zikrallah, Ahmed S."],"dc:date.accessioned":["2024-12-02T21:15:46Z"],"dc:date.available":["2024-12-02T21:15:46Z"],"dc:date.issued":["2024-09"],"dc:description.abstract":["Cytokines secretion is a core component of the function of many cell therapy products: It affects the tissue repair capacity of induced Pluripotent Stem Cells (iPSCs) and Mesenchymal Stem cells (MSCs) and the tumorigenicity of Chimeric Antigen Receptor (CAR) T-cell therapies. Ideally, we would be able to continuously monitor the secretome of these cell therapies as they are transformed and expanded in manufacturing.However, state-of-theart techniques for monitoring typically low concentrations of cytokines require either Mass Spectroscopy (MS) or immunoassays like Enzyme-linked Immunosorbent Assay (ELISA). We propose the use of CMOS technology to build a proteomic platform with a single biomolecule resolution. A prototype chip has been designed and fabricated using standard foundary process incorporating a new implementation of a Solid State Nanopore (SSN) of size 55nm×162nm×100nm (w×l×h) with nanofluidic access channels that bridge the buffer solution between the assay space in the packaging structure – a poly carbonate/Polydimethylsiloxane (PDMS) package- and the nanopore on the chip. A silicon Single Photon Avalanche Detectors (SPADs) was also implemented and placed near the nanochannels to utilize fluorescence labeling imaging techniques. In addition, a read-out amplifier that achieves a midband gain of 36.2 dB at a 3 dB bandwidth of 0.1-3.6 MHz is also implemented on the same silicon die, paving the way to superior performance compared to ionic current read-out systems used earlier for electrical biomolecule detection, thanks to low parasitics as a result of integration. The aforementioned modalities integrated on a single chip open the space for the use of CMOS platforms in the electrical and optical interrogation of biomolecules, opening a new horizon for near real-time biomarker assays. The following thesis builds on earlier work that was performed in [1][2] with the objective of expanding on different techniques to interface and characterize the performance of these modalities, especially after post-processing the chips with the aid of tools at MIT.nano. The thesis explores the further deployment of integrated SPAD in a Fluorescence Lifetime Imaging (FLIM) system to image fluorescence-labeled molecules, showcasing the capabilities of the CMOS nanofluidic platform to detect biomarkers such as cytokines."],"dc:description.degree":["S.M."],"dc:identifier.uri":["https://hdl.handle.net/1721.1/157733"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["In Copyright - Educational Use Permitted","Copyright retained by author(s)"],"dc:rights.uri":["https://rightsstatements.org/page/InC-EDU/1.0/"],"dc:title":["Towards a Single Bio-molecule Detector Based on CMOS Nanofluidic Platform"],"dc:type":["Thesis"],"thesis:degree_name":["Master","Master of Science in Media Arts and Sciences"]},"updated_at":"2026-07-22T22:21:13Z"}