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oai:dspace.mit.edu:1721.1/1577332024-12-03T03:46:49Zcom_1721.1_7582com_1721.1_7581col_1721.1_131023

Ram, Rajeev J. Zikrallah, Ahmed S. Program in Media Arts and Sciences (Massachusetts Institute of Technology) 2024-12-02T21:15:46Z 2024-12-02T21:15:46Z 2024-09 2024-11-19T19:17:23.295Z https://hdl.handle.net/1721.1/157733 https://orcid.org/0009-0007-6842-5397 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. S.M. Massachusetts Institute of Technology In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ Towards a Single Bio-molecule Detector Based on CMOS Nanofluidic Platform Thesis application/pdf Master Master of Science in Media Arts and Sciences Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="42acd5a3-22c7-40db-a7ab-c4692b47266c"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Title>Towards a Single Bio-molecule Detector Based on CMOS Nanofluidic Platform</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2024-09</PublicationDate> <Authors> <Author> <DisplayName>Zikrallah, Ahmed S.</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>https://rightsstatements.org/page/InC-EDU/1.0/</License> <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> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>