Terahertz thermal curve analysis for label-free identification of pathogens.

In this study, we perform a thermal curve analysis with terahertz (THz) metamaterials to develop a label-free identification tool for pathogens such as bacteria and yeasts. The resonant frequency of the metasensor coated with a bacterial layer changes as a function of temperature; this provides a unique fingerprint specific to the individual microbial species without the use of fluorescent dyes and antibodies. Differential thermal curves obtained from the temperature-dependent resonance exhibit the peaks consistent with bacterial phases, such as growth, thermal inactivation, DNA denaturation, and cell wall destruction. In addition, we can distinguish gram-negative bacteria from gram-positive bacteria which show strong peaks in the temperature range of cell wall destruction. Finally, we perform THz melting curve analysis on the mixture of bacterial species in which the pathogenic bacteria are successfully distinguished from each other, which is essential for practical clinical and environmental applications such as in blood culture.

Identifying different types of microorganisms with terahertz spectroscopy.

Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes. Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range. We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory. The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11. The yeasts exhibited particularly high dielectric constants reaching 5.63-5.97, which were even higher than that of water. These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials. In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment. By contrast, the deposition of the yeasts induced a red shift because their dielectric constant was higher than that of water. Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and ß-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.

FeSe quantum dots for in vivo multiphoton biomedical imaging.

An immense demand in biomedical imaging is to develop efficient photoluminescent probes with high biocompatibility and quantum yield, as well as multiphoton absorption performance to improve penetration depth and spatial resolution. Here, iron selenide (FeSe) quantum dots (QDs) are reported to meet these criteria. The synthesized QDs exhibit two- and three-photon excitation property at 800- and 1080-nm wavelengths and high quantum yield (ca. 40%), which are suitable for second-window imaging. To verify their biosuitability, poly(ethylene glycol)-conjugated QDs were linked with human epidermal growth factor receptor 2 (HER2) antibodies for in vitro/in vivo two-photon imaging in HER2-overexpressed MCF7 cells and a xenograft breast tumor model in mice. Imaging was successfully carried out at a depth of up to 500 µm from the skin using a nonlinear femtosecond laser at an excitation wavelength of 800 nm. These findings may open up a way to apply biocompatible FeSe QDs to multiphoton cancer imaging.

Enhanced sensitivity in THz plasmonic sensors with silver nanowires.

We developed hybrid slot antenna structures for microbial sensing in the THz frequency range, where silver nanowires (AgNWs) were employed to increase the sensitivity. In order to fabricate the hybrid devices, we partially etched the AgNW in the slot antenna region, where we can expect the field enhancement effect at the AgNW tip. We measured the resonant-frequency shift observed upon the deposition of a polymer layer, and observed that the sensitivity increased upon the introduction of AgNWs, with an enhancement factor of more than four times (approximately six times in terms of figure-of-merit). The sensitivity increased with the AgNW density until saturation. In addition, we tested devices with PRD1 viruses, and obtained an enhancement factor of 3.4 for a slot antenna width of 3 µm. Furthermore, we performed finite-difference time-domain simulations, which confirmed the experimental results. The sensitivity enhancement factor decreased with the decrease of the slot width, consistent with the experimental findings. Two-dimensional mapping of the electric field confirmed the strong field localization and enhancement at the AgNW tips.