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Adenosine phosphates (adenosine 5′-monophosphate (AMP), adenosine 5′-diphosphate (ADP), and adenosine 5′-triphosphate (ATP)) play important roles in energy storage and signal transduction in the human body. Thus, a measurement method that simultaneously recognizes and detects adenosine phosphates is necessary to gain insight into complex energy-relevant biological processes. Surface-enhanced Raman scattering (SERS) is a powerful technique for this purpose. However, the similarities in size, charge, and structure of adenosine phosphates (APs) make their simultaneous recognition and detection difficult. Although approaches that combine SERS and machine learning have been studied, they require massive quantities of training data. In this study, limited AP spectral data were obtained using fabricated gold nanostructures for SERS measurements. The training data were created by feature selection and data augmentation after preprocessing the small amount of acquired spectral data. The performances of several machine learning models trained on these generated training data were compared. Multilayer perceptron model successfully detected the presence of AMP, ADP, and ATP with an accuracy of 0.914. Consequently, this study establishes a new measurement system that enables the highly accurate recognition and detection of adenosine phosphates from limited SERS spectral data.

The development of a cost-effective and rapid assay technique for the identification of DNA methylation is one of the most crucial issues in the field of biomedical diagnosis because DNA methylation plays key roles in human health. The plasmonic crystal-based surface-enhanced Raman spectroscopy (SERS) technique is promising for the realization of such an assay method owing to its capability of generating uniformly enhanced electric fields to achieve high reproducibility and accuracy in SERS assays. However, the time and technical costs of fabricating plasmonic crystals are high, owing to the need for nanofabrication equipment. In this study, we developed nanoimprinted plasmonic crystals for cost-effective and rapid DNA methylation assays. Our plasmonic crystals identified methylated DNA with the 40-base pair adenomatous polyposis coli (APC) gene sequence, which is correlated with cell growth and cancer cells.

The interface between perovskite-oxide SrTiO3 and other oxides realizes efficient spin-to-charge current conversion; however, the typically insulating oxides hinder the propagation of spin-currents. Here the authors achieve a record efficiency by replacing an oxide insulator with a strongly-correlated polar metal.

Metal nanostructures have attracted attention because of their unique optical characteristics derived from localized surface plasmon resonance. In this study, gold nanoholes with edge structures were designed and characterized to possess two plasmon bands at different wavelengths. These bands were assigned to the plasmon modes that generated a concentrated electric field at the tip of the individual edge structures. Furthermore, wavelengths of these bands were independently tuned from the visible to near-infrared wavelengths with shape and size of the gold nanoholes and edge structures as variables. To demonstrate wavelength tuning, a gold nanostructure with edge plasmon bands at wavelengths of approximately 785 and 1064 nm (typical laser wavelengths for surface-enhanced Raman scattering and optical tweezers, respectively) was successfully obtained via optical simulation. The results indicate that the structure designed in this study provides a guideline for the design of optical devices with efficient multiple optical functions.

This study reports a novel aptamer selection method based on microscale electrophoretic filtration. Aptamers are versatile materials that recognize specific targets and are attractive for their applications in biosensors, diagnosis, and therapy. However, their practical applications remain scarce due to issues with conventional selection methods, such as complicated operations, low-efficiency separation, and expensive apparatus. To overcome these drawbacks, a selection method based on microscale electrophoretic filtration using a capillary partially filled with hydrogel was developed. The electrophoretic filtration of model target proteins (immunoglobulin E (IgE)) using hydrogel, the electrokinetic injection of DNAs to interact with the trapped proteins, the elimination of DNAs with weak interactions, and the selective acquisition of aptamer candidates with strong interactions were successfully demonstrated, revealing the validity of the proposed concept. Two aptamer candidates for IgE were obtained after three selection cycles, and their affinity for the target was confirmed to be less than 1 nM based on their dissociation constant (KD) values. Therefore, the proposed method allows for the selection of aptamers with simple operations, highly effective separation based on electrophoresis and filtration, and a relatively cheap apparatus with disposable devices.

A quartz crystal microbalance (QCM) is a sensor that uses the piezoelectric properties of quartz crystals sandwiched between conductive electrodes. Localized surface plasmon resonance (LSPR) is an analytical technique that uses the collective vibration of free electrons on metal surfaces. These measurements are known as analysis techniques that use metal surfaces and have been applied as biosensors because they allow for the label-free monitoring of biomolecular binding reactions. These measurements can be used in combination to analyze the reactions that occur on metal surfaces because different types of information can be obtained from them. However, as different devices are used for these measurements, the results often contain device-to-device errors and are not accurately evaluated. In this study, we directly fabricated gold nanostructures on the surface of a QCM to create a device that can simultaneously measure the mass and refractive index information of the analyte. In addition, the device could be easily fabricated because nanoimprint lithography was used to fabricate gold nanostructures. As a proof of concept, the nanoparticle adsorption on gold nanostructures was evaluated, and it was observed that mass and refractive index information were successfully obtained without device-to-device errors.

Surface-enhanced Raman scattering (SERS) is a technique used to distinguish the constitution of disease-related biomarkers in liquid biopsies, such as exosomes and circulating tumor cells, without any recognition elements. Previous studies using metal nanoparticle aggregates and angular nanostructures have achieved the detection of various biomarkers owing to strong hot spots and electromagnetic (EM) fields by localized surface plasmon resonance (LSPR). Although these SERS platforms enable significant enhancement of Raman signals, they still have some problems with the fabrication reproducibility of platforms in obtaining reproducible SERS signals. Therefore, highly reproducible fabrication of SERS platforms is required. Here, we propose the application of a polymer-based gold (Au) nanocone array (Au NCA), which extensively generates an enhanced EM field near the Au NCA surface by LSPR. This approach was experimentally demonstrated using a 785 nm laser, typically used for SERS measurements, and showed excellent substrate-to-substrate reproducibility (relative standard deviation (RSD) < 6%) using an extremely simple fabrication procedure and very low laser energy. These results proved that a Au NCA can be used as a highly reproducible SERS measurement to distinguish the constitution of biomarkers.

In this study, we report an inkjet printing-based method for the immobilization of different reactive analytical reagents on a single microchannel for a single-step and homogeneous solution-based competitive immunoassay. The immunoassay microdevice is composed of a poly(dimethylsiloxane) microchannel that is patterned using inkjet printing by two types of reactive reagents as dissolvable spots, namely, antibody-immobilized graphene oxide and a fluorescently labeled antigen. Since nanoliter-sized droplets of the reagents could be accurately and position-selectively spotted on the microchannel, different reactive reagents were simultaneously immobilized onto the same microchannel, which was difficult to achieve in previously reported capillary-based single-step bioassay devices. In the present study, the positions of the reagent spots and amount of reagent matrix were investigated to demonstrate the stable and reproducible immobilization and a uniform dissolution. Finally, a preliminary application to a single-step immunoassay of C-reactive protein was demonstrated as a proof of concept.

The coronavirus disease (COVID-19) caused by SARS-CoV-2 has caused a global pandemic. To manage and control the spread of the infection, it is crucial to develop and implement technologies for the early identification of infected individuals and rapid informatization in communities. For the realization of such a technology, a widely available and highly usable sensor for sensitive and specific assay of the virus plays a fundamental role. In this study, we developed an optical sensor based on an imprinted photonic crystal film (IPCF) for quick, simple, and cost-effective detection of SARS-CoV-2 spike protein in artificial saliva. Our IPCF sensor enabled label-free and highly sensitive detection with a smartphone-equipped optical setup. The IPCF surface was functionalized with an anti-SARS-CoV-2 spike protein antibody for immunoassay. We evaluated the specificity and sensitivity of the IPCF sensor for quantitative detection of the spike protein in artificial saliva using simple reflectometry with a spectrometer-equipped optical setup. Specific and quantitative detection of the spike protein was successfully achieved, with a low detection limit of 429 fg/mL. In the demonstration of reflectometric detection with a smartphone-equipped setup, the sensitivity was comparable with that with a spectrometer-equipped setup. The test result is returned immediately and can be saved to cloud storage. In addition, it costs less than USD 1 for one IPCF to be used for diagnosis. Thus, the developed IPCF has the potential to realize a widely available and highly usable sensor.

In this paper, metal–insulator–metal (MIM) nanostructures, which were designed to exhibit two absorption peaks within 500–1100 nm wavelength range, were fabricated using magnesium difluoride (MgF2) as the insulator layer. Since the MIM nanostructures have two plasmon modes corresponding to the absorption peaks, they independently responded to the changes in two phases: the surrounding medium and the inside insulator layer, the structure is expected to obtain multiple information from sample solution: refractive index (RI) and molecular interaction between solution components and the insulator layer. The fabricated MIM nanostructure had a diameter of 139.6 ± 2.8 nm and a slope of 70°, and exhibited absorption peaks derived from individual plasmon modes at the 719 and 907 nm wavelengths. The evaluation of the response to surrounding solution component of the MIM nanostructures revealed a linear response of one plasmon mode toward the RI of the surrounding medium and a large blue shift of the other plasmon mode under conditions where glycerol was present at high concentration. From optical simulation and the evaluation of the MgF2 fabricated by deposition, the blue shift was expected to be due to the swelling of MgF2 interacting with the hydroxyl groups abundantly included in the glycerol molecules. The results indicated the individual responses of two plasmon modes in MIM nanostructures toward medium components, and brought the prospect for the simultaneous measurement of multiple elements using two or more plasmon modes.

Metal nanostructures exhibit specific optical characteristics owing to their localized surface plasmon resonance (LSPR) and have been studied for applications in various optical devices. The LSPR property strongly depends on the size and shape of metal nanostructures; thus, plasmonic devices must be designed and fabricated according to their uses. Nanoimprint lithography (NIL) is an effective process for repeatedly fabricating metal nanostructures with controlled sizes and shapes and require optical properties. NIL is a powerful method for mass-producible, low-cost, and large-area fabrication. However, the process lacks flexibility in adjusting the size and shape according to the desirable optical characteristics because the size and shape of metal nanostructures are determined by a single corresponding mold. Here, we conducted a re-shaping process through the air-plasma etching of a polymer’s secondary mold (two-dimensional nanopillar array made of cyclo-olefin polymer (COP)) to modulate the sizes and shapes of nanopillars; then, we controlled the spectral characteristics of the imprinted plasmonic devices. The relationship between the structural change of the mold, which was based on etching time, and the optical characteristics of the corresponding plasmonic device was evaluated through experiments and simulations. According to evaluation results, the diameter of the nanopillar was controlled from 248 to 139 nm due to the etching time and formation of a pit structure. Consequently, the spectral properties changed, and responsivity to the surrounding dielectric environment was improved. Therefore, plasmonic devices based on the re-shaped COP mold exhibited a high responsivity to a refractive index of 906 nm/RIU at a wavelength of 625 nm.

Surface-enhanced Raman scattering (SERS) is a potential candidate for highly sensitive detection of target molecules. A SERS active substrate with a noble metal nanostructure is required for this. However, a SERS active substrate requires complicated fabrication procedures. This in turn makes it difficult to fabricate highly sensitive SERS active substrates with high reproducibility. To overcome this difficulty, a plasmonic crystal (PC) with periodic noble metal nanostructures was fabricated via the template-stripping method using a polymer-based template. Using SERS active substrates, SERS was successfully achieved using the PC by detecting low concentrations of phenobarbital which is an antiepileptic drug using a commercially available portable Raman module. The PC can be fabricated by demolding the deposited gold layer from a polymer-based template. This method is rapid, economic, and has high reproducibility. SERS can be achieved easily using this PC for a wide variety of applications such as medical, pharmaceutical, and environmental protection.

Exosomes, a type of extracellular vesicle with a diameter of 30–150 nm, perform key biological functions such as intercellular communication. Recently, size sorting of exosomes has received increasing attention in order to clarify the correlation between their size and components. However, such sorting remains extremely difficult. Here, we propose to sort their size by controlling their electrokinetic migration in nanochannels in a micro-nanofluidic device, which is achieved by tuning the thickness of the electric double layers in the nanochannels. This approach was demonstrated experimentally for exosomes smaller than 250 nm. Using different running buffer concentrations (1 × 10−3, 1 × 10−4, and 1 × 10−5 M), most of the exosomes larger than 140, 110, and 80 nm were successfully cut off at the downstream of the nanochannels, respectively. Therefore, it is clarified that the proposed method is applicable for the size sorting of exosomes.

Congo Red (CR) and Amido Black 10B (AB-10B) are anionic diazo dyes, which are metabolized to produce a bioaccumulative and persistent carcinogen, benzidine. In this regard, an angle sensitive sensor composed of photonic crystal supported photocatalyst was fabricated for the simultaneous detection and photocatalytic degradation of diazo dyes from aqueous solutions. Reflectance spectroscopy was used in the detection of CR and AB-10B, which was based on the emergence of the incident angle dependent reflection peaks from the TiO2 coated two-dimensional photonic crystal (2D-PhC) surfaces and their subsequent quenching due to the presence of dye molecules whose absorbance peak intensity overlapped the reflection peak intensity of TiO2 at the respective angle. Interestingly, ultraviolet (UV) mediated photocatalytic degradation of CR and AB-10B was achieved using the same TiO2 coated 2D-PhC surfaces. 2D-PhC underneath the TiO2 layer was able to confine and localize the light on the TiO2 coated 2D-PhC surface, which enhanced the light absorption by dye molecules on the TiO2 surface and the photocatalytic efficiency in the degradation of CR and AB-10B. Finally, this proof-of-concept study demonstrated the fabrication of copolymer film based photonic crystal supported photocatalytic device, which can be used for developing miniaturized sensors competent in on-field detection and degradation of pollutants.

In this paper, we have proposed a polymer-based photonic crystal (PhC) resonator, with multiple sizes of cavities, and a waveguide to be used as highly sensitive optical sensor components. Properties of the proposed PhC were simulated by the finite-difference time-domain method, and the polymer-based PhC resonator and waveguide were fabricated on a photoresist (polymer) by electron beam lithography, which was prepared on an Au-layer-deposited Si substrate. We detected the resonant light that penetrated through the waveguide and was trapped in the PhC resonator. Optical characteristics of the fabricated PhC were evaluated by detecting the polymer layer deposition process by using the layer-by-layer (LbL) method to deposit polymer layers. As a result, by using an optimized design of a polymer-based PhC resonator with a long cavity (equivalent to a defect of three holes), the PhC structure changes caused by LbL deposition lead to changes in resonant light wavelength (peak shift: 5.26 nm/layer). Therefore, we suggest that a PhC resonator and a waveguide is applicable as an optical sensor.

Polymer-based photonic crystals (PhCs) were fabricated using nanoimprint lithography for use as DNA biosensors by immobilizing the probe DNA. Polymer-based PhCs can be applied to cost-effective and label-free DNA biosensors. Additionally, DNA hybridization can be detected using inexpensive and simple optical systems. In this study, probe DNA was immobilized on the PhC surface using electrostatic adsorption or covalent bonding, and the sensing performance was compared. Consequently, the PhC biosensor prepared using covalent bonding exhibited greater DNA-hybridization-induced reflection intensity changes than that prepared using electrostatic adsorption. Furthermore, discrimination of reflection intensity for target and mismatch DNA was investigated, which revealed that in contrast to the PhC biosensor prepared using the electrostatic adsorption of probe DNA, that prepared using covalent bonding discriminated target DNA at a concentration of 0.1 nM. [ABSTRACT FROM AUTHOR]