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Semiconductor technologies for nanoelectronic diagnostics and optoelectronic therapies
Dissertation   Open access

Semiconductor technologies for nanoelectronic diagnostics and optoelectronic therapies

Daniel W Keefe
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2024
DOI: 10.25820/etd.007636
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Abstract

Semiconductors are ubiquitous in modern optics and electronics devices. Optoelectronic semiconductor devices have evolved from millimeter to nanometer scale over the past decades. In this Ph.D. dissertation, we report work on three projects that develop and analyze innovative leading-edge optoelectronics. In the first project, we discuss our development of a highly selective and sensitive silicon nanowire biosensor platform for use in point-of-care diagnosis and disease monitoring. In our second project, we develop a numerical model using COMSOL Multiphysics that utilizes ray optics and bioheat transfer physics to determine safety considerations for NeuroBlate© procedures that utilize a high power near-infrared (NIR) laser system. In our third project, we demonstrate the use of quantum engineered solid state mid-infrared (MIR) quantum cascade lasers (QCLs) for photothermal ablation of soft tissues and develop advanced optical components for coupling these new type of semiconductor lasers into MIR transparent fibers utilizing ray optics modeling for surgical applications. Biosensors are an emerging technology for detecting the presence of biochemical agents in blood samples representative of disease pathologies, which offer inexpensive and rapid testing. In this work we develop a semiconductor biosensor platform using a vertically-oriented silicon nanowire (vSiNW) array, which is portable, easy to use, and generates a concentration dependent electrical current signal that can be measured using an inexpensive current sensor. Our biofunctionalized vSiNW biosensors have previously been demonstrated to be sensitive and selective in detecting colorectal cancer (CRC) antigens at clinically relevant concentrations. In this work, we further evaluate our biosensor platform to the detection of CRC circulating tumor DNA (ctDNA) to support low-cost and time-effective analysis of liquid biopsy samples of cancer patients. Our preliminary fluoroscopy results indicate that the vSiNW platform can be functionalized and incubated with low concentrations of capture and target DNA. They also show specificity for wild type compared to common one/two/full base-pair mismatch mutations. We propose to expand upon these promising results by evaluating the electrical response of the biosensor to the presence of ctDNA in liquid analyte. Magnetic resonance guided laser interstitial thermal therapy (MRgLITT) is a near infrared (NIR) laser surgical ablation procedure in which a laser probe is inserted into the target tissue and emits high power (>10 W) NIR radiation to photothermally ablate the surrounding tissue. This procedure has been well-used in treating neuropathologies such as focal epilepsies. There is growing interest in combining MRgLITT with other techniques, such as stereoelectroencephalography (sEEG), which would involve placing metal/polymer sEEG electrodes near the high power NIR laser applicator. In this work, we apply finite element method (FEM) numerical modeling software, COMSOL Multiphysics, to model the NeuroBlate© procedure in the brain taking into account blood perfusion, metabolic heat generation, and the presence of proximal sEEG electrodes. We find that models with bioheat transfer result in lower temperatures (Tmax = 53℃) than those without (Tmax = 64℃) after four minutes of ablation, and by extension they have smaller ablated volumes (1.1-cm3) than models without bioheat transfer (2.6-cm3). We also find that the presence of sEEG electrodes does not significantly affect the maximum temperature or damaged tissue volume, but it does cause slight temperature and damage differences in the electrode-contacting tissue compared to when there were no electrodes present. Our results show the impact of sEEG electrodes on the NIR laser based MRgLITT procedure that can be utilized to inform neurosurgeons about safety considerations during such procedures. NIR laser ablation systems are limited by the relatively low optical absorption coefficient of biological tissue that results in deep ablation zones damaging surrounding healthy tissue during surgical procedures. On the other hand, MIR wavelength band exhibits orders of magnitude higher absorption coefficient of biological tissue which results in more precise surgical ablation than NIR ablation techniques. Little work has been done to prove the feasibility of MIR QCLs for photothermal ablation. In this work, we report results on the efficacy and spatial precision of two MIR QCLs (λ0 = 4.60, 4.65 µm) for photothermal ablation of agarose cell cultures (COLO205), chicken breast tissue, and porcine liver and pulmonary vein tissue. With the former QCL wavelength, we demonstrate effective ablation of agarose cell cultures (COLO205). With the latter, we explored the relationship between laser ablation settings and the resultant ablated diameter and depth in chicken tissue. We found that the extent of ablation increases with laser power, pulse duty cycle, and exposure duration, but is independent of pulse frequency for any tested combination of frequency and power. We also performed preliminary ablation experiments with the 4.65-µm QCL on porcine tissue, and chicken breast via an optical fiber. We found that this QCL is an effective source for laser ablation in these tissues. Which encourages further development of this technology. We perform theoretical simulations of the ablation using COMSOL and experimental chicken tissue ablation for different MIR QCL operation parameters to determine the efficacy and precision of MIR lasers. Our preliminary results confirm the efficacy of 4.65-µm MIR photothermal ablation, agreeing with experimental results, and promote further modeling development.
Computational Physics biosensor COMSOL nanowire neuroblate quantum cascade laser soft tissue ablation

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