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Micro-Nanotechnology Platforms for Monitoring Neural Cell Secretion and Culturing Neurospheroids.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Micro-Nanotechnology Platforms for Monitoring Neural Cell Secretion and Culturing Neurospheroids./
作者:	Yang, Renyuan.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2022,
面頁冊數:	88 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-12, Section: B.
Contained By:	Dissertations Abstracts International83-12B.
標題:	Electrical engineering. -
ISBN:	9798819384688

Micro-Nanotechnology Platforms for Monitoring Neural Cell Secretion and Culturing Neurospheroids.
Yang, Renyuan.

Micro-Nanotechnology Platforms for Monitoring Neural Cell Secretion and Culturing Neurospheroids. - Ann Arbor : ProQuest Dissertations & Theses, 2022 - 88 p.

Source: Dissertations Abstracts International, Volume: 83-12, Section: B.

Thesis (Ph.D.)--Iowa State University, 2022.

This item must not be sold to any third party vendors.

As the aging population becomes a growing global trend, more and more people are afflicted by neurodegenerative disorders (NDD). It has been found that transcranial magnetic stimulation (TMS) has therapeutic effect on the NDD. The TMS has been approved by the FDA for the clinical treatment for the depression. However, the molecular-level principle underlying the TMS effect is not clear so far. Glial cell derived neurotrophic factors (GDNF) is considered to play an important role in protecting and restoring dopaminergic neurons and motor neurons, and thus has great value to develop treatment on Parkinson's disease. Detection of GDNF level becomes increasing important for studies on the GDNF. Recently, brain-on-a-chip platforms has drawn tremendous attention from the research community, due to its merits: low cost, high efficiency, high throughput, better mimicking in vivo environment, potential to replace animal models. The brain-on-a-chip platforms can provide an excellent in vitro model to study the neurogenesis, NDD pathology, drug screening and so on. Understanding the behaviors of neural cells and establishing in vitro brain models are critically important for exploring potential treatments.My research work consists of two parts: (1) an optical thin-film biosensor has been developed to study the TMS effect on the secretion of GDNF from N27 cells. The sensor consists of nanopore thin film, prepared by E-beam evaporation, anodic oxidation and sputtering process. The porous surface is functionalized with GDNF antibodies. The detection principle is based on light interference as the thin-film biosensor acts like Fabry-Perot interferometer. GDNF molecule binding on the sensor surface causes effective thickness or refractive index change, giving rise to interference pattern change. This type of nanosensor offers significantly improved limit of detection for GDNF and good specificity. We found that the TMS can promote GDNF secretion from N27 cells, which may constitute a plausible reason to explain the TMS therapeutic effect on the NDD. (2) A microfluidic platform has been developed to culture and analyze in vitro brain models on chip. COMSOL Multiphysics is used to simulate the working principle of the microfluidic device. The simulation result can help design the microfluidic chip, which is then fabricated by soft lithography and reflow process. The microchambers for cell culturing are 360 µm in diameter and 150-200 µm in depth. Rat adult hippocampal progenitor cells (AHPCs) are used as cell model. The cells are seeded into the chip and cultured for 12 days. The daily images of the cells on chip show that the cells can live, proliferate, form cell clusters and eventually develop into neurospheroids. Biomarkers are used to evaluate cell viability, proliferation and neural differentiation in the neurospheroids. The cell viability is found to be high in the chip, exhibiting a good device biocompatibility. The cells keep a constant proliferation rate throughout 12 days. The size of the neurospheroids keeps growing due to cell proliferation and aggregation. The differentiation results reveal that the AHPCs can differentiate into astrocytes, oligodendrocytes, immature and mature neurons. Besides, the microfluidic chip can support on-chip high-resolution confocal fluorescence imaging, a powerful tool for advanced cell analysis. So, our microfluidic platform allows on-chip study of cell viability, proliferation, and neuronal differentiation. Our work shows the feasibility to culture AHPC neurospheroid as a suitable in vitro brain model on chip.

ISBN: 9798819384688Subjects--Topical Terms:

649834
Electrical engineering.
Subjects--Index Terms:

Anodic aluminum oxide

Micro-Nanotechnology Platforms for Monitoring Neural Cell Secretion and Culturing Neurospheroids.
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500 $a Source: Dissertations Abstracts International, Volume: 83-12, Section: B.
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506 $a This item must not be sold to any third party vendors.
520 $a As the aging population becomes a growing global trend, more and more people are afflicted by neurodegenerative disorders (NDD). It has been found that transcranial magnetic stimulation (TMS) has therapeutic effect on the NDD. The TMS has been approved by the FDA for the clinical treatment for the depression. However, the molecular-level principle underlying the TMS effect is not clear so far. Glial cell derived neurotrophic factors (GDNF) is considered to play an important role in protecting and restoring dopaminergic neurons and motor neurons, and thus has great value to develop treatment on Parkinson's disease. Detection of GDNF level becomes increasing important for studies on the GDNF. Recently, brain-on-a-chip platforms has drawn tremendous attention from the research community, due to its merits: low cost, high efficiency, high throughput, better mimicking in vivo environment, potential to replace animal models. The brain-on-a-chip platforms can provide an excellent in vitro model to study the neurogenesis, NDD pathology, drug screening and so on. Understanding the behaviors of neural cells and establishing in vitro brain models are critically important for exploring potential treatments.My research work consists of two parts: (1) an optical thin-film biosensor has been developed to study the TMS effect on the secretion of GDNF from N27 cells. The sensor consists of nanopore thin film, prepared by E-beam evaporation, anodic oxidation and sputtering process. The porous surface is functionalized with GDNF antibodies. The detection principle is based on light interference as the thin-film biosensor acts like Fabry-Perot interferometer. GDNF molecule binding on the sensor surface causes effective thickness or refractive index change, giving rise to interference pattern change. This type of nanosensor offers significantly improved limit of detection for GDNF and good specificity. We found that the TMS can promote GDNF secretion from N27 cells, which may constitute a plausible reason to explain the TMS therapeutic effect on the NDD. (2) A microfluidic platform has been developed to culture and analyze in vitro brain models on chip. COMSOL Multiphysics is used to simulate the working principle of the microfluidic device. The simulation result can help design the microfluidic chip, which is then fabricated by soft lithography and reflow process. The microchambers for cell culturing are 360 µm in diameter and 150-200 µm in depth. Rat adult hippocampal progenitor cells (AHPCs) are used as cell model. The cells are seeded into the chip and cultured for 12 days. The daily images of the cells on chip show that the cells can live, proliferate, form cell clusters and eventually develop into neurospheroids. Biomarkers are used to evaluate cell viability, proliferation and neural differentiation in the neurospheroids. The cell viability is found to be high in the chip, exhibiting a good device biocompatibility. The cells keep a constant proliferation rate throughout 12 days. The size of the neurospheroids keeps growing due to cell proliferation and aggregation. The differentiation results reveal that the AHPCs can differentiate into astrocytes, oligodendrocytes, immature and mature neurons. Besides, the microfluidic chip can support on-chip high-resolution confocal fluorescence imaging, a powerful tool for advanced cell analysis. So, our microfluidic platform allows on-chip study of cell viability, proliferation, and neuronal differentiation. Our work shows the feasibility to culture AHPC neurospheroid as a suitable in vitro brain model on chip.
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710 2 0 $a Iowa State University. $b Electrical and Computer Engineering. $3 1018524
773 0 $t Dissertations Abstracts International $g 83-12B.
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