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Development and optimization of a biosensor platform based on metamaterials

Development and optimization of a biosensor platform based on metamaterials

초록/요약

Microorganisms such as fungi and bacteria cause many human diseases and therefore rapid and accurate identification of these substances is essential for effective treatment and prevention of further infections. In particular, contemporary microbial detection technique is limited by the low detection speed which usually extends over a couple of days. In this thesis, we develop and optimize a biosensor platform based on metamaterials that are capable of high-speed on-site detection of target materials in both ambient and aqueous environments. We begin with the first demonstration of microorganisms using metamaterials. We were able to detect extremely small amounts of the microorganisms because their sizes are on the same scale as the micro-gaps of the terahertz metamaterials. The resonant frequency shift of the metamaterials was investigated in terms of the number density and the dielectric constants of the microorganisms, which was successfully interpreted by the change in the effective dielectric constant of a gap area. Furthermore, we demonstrate dielectric substrate effects on the resonance shift of terahertz metamaterials with various metal thicknesses by using finite-difference time-domain simulations. We found a small red shift in the metamaterial resonance with increasing metal thickness for the free-standing case. Conversely, when the metamaterial pattern was supported by a substrate with a high dielectric constant, the resonant frequency exhibited a large blue shift because the relative contribution of the substrate’s refractive index to the resonant frequency decreased drastically as we increased the metal thickness. We determined the substrate’s refractive index, 1.26, at which the metamaterial resonance was independent of the metal thickness. We extracted the effective refractive index as a function of the substrate’s refractive index explicitly, which was noticeably different for different film thicknesses. We demonstrated sensitive detection of individual yeast cells and yeast films by using slot antenna arrays operating in the terahertz frequency range. Microorganisms located at the slot area cause a shift in the resonant frequency of the THz transmission. The shift was investigated as a function of the surface number density for a set of devices fabricated on different substrates. In particular, sensors fabricated on a substrate with relatively low permittivity demonstrate higher sensitivity. The frequency shift decreases with increasing slot antenna width for a fixed coverage of yeast film, indicating a field enhancement effect. Furthermore, the vertical range of the effective sensing volume has been studied by varying the thickness of the yeast film. The resonant frequency shift saturates at 3.5 μm for a slot width of 2 μm. The shape dependence of target materials on the sensitivity of terahertz metamaterial sensors was also investigated. Polystyrene microbeads with a known dielectric constant and spherical, ovular, lens-shaped, and star-shaped structures were studied. The resonant frequency showed a clear red-shift after the deposition of low-density microbeads owing to the change in the dielectric environment in the gap area of the metamaterials. The shift in the resonant frequency increased linearly with the surface density, saturating at 60–80 GHz when the gap area was full of microbeads. More importantly, the resonant frequency shift was higher for non-spherical microbeads, such as the star-shaped microbeads. Therefore, the shape of the individual target material was a crucial factor in determining metamaterial sensor sensitivity. We studied experimentally and theoretically the vertical range of the confined electric field in the gap area of metamaterials, which was analyzed for various gap widths using terahertz time-domain spectroscopy. We measured the resonant frequency as a function of the thickness of poly(methyl methacrylate) in the range 0 to 3.2 μm to quantify the effective detection volumes. We found that the effective vertical range of the metamaterial is determined by the size of the gap width. The vertical range was found to decrease as the gap width of the metamaterial decreases, whereas the sensitivity is enhanced as the gap width decreases due to the highly concentrated electric field. Finally, a numerical expression was obtained for the vertical range as a function of the gap width. This expression is expected to be very useful for optimizing the sensing efficiency. We also demonstrate that terahertz metamaterials are powerful tools for determination of dielectric constants of polymer films and polar liquids. As we deposit a dielectric film on a metamaterial, the resonant frequency shifts, but saturates at a specific thickness due to the limited sensing volume of the metamaterial. From the saturated value, we can extract the dielectric constants of various polymers that are transparent to the THz frequency range. In addition, we fabricated a microfluidic channel that contains the metamaterials to address the real dielectric constants for a polar liquid solution. This was possible due to an extremely confined electric field near the gap area of the metamaterials, enabling us to employ very thin liquid layers. We found that the resonance shifts do not depend critically on the imaginary dielectric constants, proving that our approach can be universal in terms of various materials, including absorptive materials. As an example, the dielectric constants of sodium chloride and potassium chloride solutions have been determined with various concentrations. Finally, we demonstrate highly sensitive detection of viruses using terahertz split-ring resonators with various capacitive gap widths. Two types of viruses, with sizes ranging from 60 nm (PRD1) to 30 nm (MS2), were detected at low densities on the metamaterial surface. The dielectric constants of the virus layers in the THz frequency range were first measured using thick films, and the large values found identified them as efficient target substances for dielectric sensing. We observed the resonance-frequency shift of the THz metamaterial following deposition of the viruses on the surface at low-density. The resonance shift was higher for the MS2 virus, which has a relatively large dielectric constant. The frequency shift increases with surface density until saturation and the sensitivity is then obtained from the initial slope. Significantly, the sensitivity increases by about 13 times as the gap width in the metamaterials is decreased from 3 µm to 200 nm. This results from a combination of size-related factors, leading to field enhancement accompanying strong field localization.

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목차

Chapter 1 1
Introduction 1
1.1 Definition of metamaterials 1
1.2 Current trends in biosensor research 3
1.3 Organization of the thesis 4
References 8
Chapter 2 10
Terahertz Metamaterials 10
2.1 Magnetic and electric responses of metamaterials 10
2.2 Equivalent circuit model of THz metamaterials 13
2.3 Dielectric sensing with planar THz-metamaterials 13
2.4 THz Time-Domain Spectroscopy 15
References 17
Chapter 3 18
THz Metamaterials as a Biosensor 18
3.1 Introduction 18
3.2 Detection of microorganisms using THz metamaterials 20
3.3 Selective detection of E. coli in aqueous environment 23
3.4 Quantitative study on the resonant frequency shift 25
3.5 Dielectric constants of microorganisms 28
3.6 Finite-Difference Time-Domain (FDTD) simulation 30
3.7 Method 33
3.8 Conclusion 35
References 36
Chapter 4 41
Substrate Effects on THz Metamaterials Resonances for Various Metal Thicknesses 41
4.1 Introduction 41
4.2 Resonant frequency of THz metamaterials for various metal thicknesses 43
4.3 Effects of the substrate index and the metal thickness on metamaterials resonances 44
4.4 Relation between the effective index and the substrate index 47
4.5 Conclusion 48
References 50
Chapter 5 52
Sensitive Detection of Yeast using THz Slot Antenna 52
5.1 Introduction 52
5.2 Detection of yeast cells using THz slot antennas 54
5.3 Substrate effects on the sensitivity 55
5.4 The effects of geometrical factors and vertical range of the effective sensing volume 57
5.5 FDTD simulation 59
5.6 Method 60
5.7 Conclusion 61
References 63
Chapter 6 66
Effects of Target Shape on the Sensitivity of Metamaterials Sensors 66
6.1 Introduction 66
6.2 THz metamaterials sensing on polystyrene microbeads 67
6.3 Shape dependence of the sensitivity of THz metamaterials sensors 71
6.4 Method 73
6.5 Conclusion 74
References 76
Chapter 7 78
Effective Sensing Volume of THz Metamaterials with Various Gap Widths 78
7.1 Introduction 78
7.2 THz metamaterials sensors with various gap widths 80
7.3 Effective sensing volume and the sensitivity of THz metamaterials sensors for various gap widths 82
7.4 FDTD simulation 83
7.5 Method 85
7.6 Conclusion 86
References 87
Chapter 8 89
Dielectric Constant Measurements of Thin Films and Liquids using THz Metamaterials 89
8.1 Introduction 89
8.2 Saturation behavior of THz metamaterials with increasing target materials thickness 91
8.3 Dielectric constant measurement of polymer films using THz metamaterials 95
8.4 Fluidic THz metamaterials sensor for measuring dielectric constant of liquid 96
8.5 Dielectric constant measurement of liquids with various ionic concentrations 98
8.6 Method 100
8.7 Conclusion 101
References 103
Chapter 9 106
Sensing Viruses using THz Nano Gap Metamaterials 106
9.1 Introduction 106
9.2 THz nano-gap metamaterials sensors 107
9.3 Dielectric constant measurement of virus layer using THz metamaterials 109
9.4 Detection of PRD1, MS2 viruses 111
9.5 Field enhancement effect on the sensitivity of THz metamaterials sensors 112
9.6 Method 114
9.7 Conclusion 115
References 117
Conclusion 120
Appendix A 124
Crystallization Kinetics of Lead Halide Perovskite Film Monitored by In-situ THz-TDS 124
A.1 Introduction 124
A.2 In-situ THz TDS 126
A.3 Phase transformation of lead halide perovskite film 128
A.4 Transition of perovskite growth dimensionality 129
A.5 UV-induced crystallization and decrystallization process 130
A.6 Photo-inudced structural change in perovskite film 132
A.7 Method 135
A.8 Conclusion 137
References 139
Publications list 143

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