Author ORCID Identifier

https://orcid.org/0000-0002-8070-5355

Semester

Summer

Date of Graduation

2023

Document Type

Dissertation

Degree Type

PhD

College

Statler College of Engineering and Mineral Resources

Department

Mechanical and Aerospace Engineering

Committee Chair

Konstantinos Sierros

Committee Co-Chair

Peng Li

Committee Member

Peng Li

Committee Member

Yuxin Liu

Committee Member

Xingbo Liu

Committee Member

Edward Sabolsky

Abstract

Microfluidics are valuable devices in the biomedical field because of their remarkable ability to manipulate small volumes of fluid and facilitate reactions. Microfluidics have several significant advantages, including their portability, low cost, fast reaction times, and high surface area-to-volume ratios. Microfluidics be used for a multitude of applications, including bioanalysis, cellular assays, organ-on-a-chip, and separations. Microfluidics have great potential to overcome many challenges in conventional chemical and biological applications. However, complex fabrication procedures in silicon, glass, thermoplastics, and (polydimethylsiloxane) PDMS devices make rapidly optimizing and prototyping devices challenging. Microfluidic fabrication techniques have been a long-standing challenge in successfully translating these devices into practical and commercial applications.

3D printing technology has emerged as a promising alternative in microfluidics fabrication because it can affordably and rapidly prototype devices. 3D printing is a cost-effective, rapid prototyping technology that offers extraordinary design flexibility. It overcomes the extensive design delays seen with other microfluidic device materials. Yet, 3D printing for microfluidics is limited by the available printing technology, as print resolution and direct translation of microfluidics designs still need to be improved. Therefore, to further 3D printed microfluidic technology, there is a need for innovative strategies to expand and demonstrate their functionality. In this dissertation, two 3D-printed microfluidic devices were studied for advanced fluid manipulation and rapid fluid mixing in biomedical applications. The overall outcome of this work is to expand and demonstrate the possibilities for 3D printed microfluidic devices for nucleic acid biosensing and nanoparticle fabrication.

First, a 3D printed microfluidic device was designed to enable simple fluid manipulation for a multi-stepped nucleic acid assay. The device uses a miniaturized microwell plate with a microfluidic channel loading system to load the device with ease and without cross reactivity. The design allows for high throughput multiplexing and multistep reactions without complex fluid handling or external equipment. The device easily combined loop-mediated isothermal amplification (LAMP) and CRISPR-Cas12a readout in a simple and high-throughput workflow with low reagent consumption. To ensure the maximum performance of the device, the concentration of Cas12a and detection probe was optimized, which yielded a four-fold sensitivity improvement. The device achieved multiplexed detection of four genomic DNA targets with detection limits ranging from 1 fg/mL to 10 fg/mL within one hour.

The second 3D printed microfluidic device is easily integrated with an active mixing strategy via vibrating sharp-tip capillary device to facilitate microfluidic mixing for nanoparticle synthesis. 3D printed microfluidics are a good alternative to PDMS devices because they are affordable to produce and can be more easily integrated with active mixing strategies. By using a 3D printed device, the vibrating sharp-tip capillary mixer is easily integrated into the device. In the first application, the device was applied for gold nanostar synthesis. To date, 3D printed microfluidic devices have not been applied to synthesize complex metallic nanostructure. The device offers simple programmability to synthesize gold nanostars with various physical and optical properties. The vibrating sharp-tip mixing device can mix three streams of fluid across ~300 mm within 7 ms. The device operates with flow rates ranging from 10 mL min to 750 mL/min at low power requirements (2 – 45 mW). The optical properties of the resulting nanostars are easily tuned from 550 nm to 850 nm by modulating the input flow rate. Thus, the presented 3D printed microfluidic device produces high-quality gold nanostars with tunable optical and physical properties suitable for extensive applications.

Finally, the vibrating sharp-tip capillary microfluidic device is applied to facilitate microfluidic mixing for lipid nanoparticle synthesis. Typically, staggered herringbone devices are used for lipid nanoparticle synthesis. However, they suffer from complex fabrication, channel clogging, and long mixing lengths, which require careful optimization of the total flow rate, flow rate ratios, and lipid concentration. The device offers rapid mixing over a short mixing length.

Embargo Reason

Publication Pending

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