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Huntington's disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs-JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its β-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs-JLD1, we generated a complex (AuNPs-JLD1-PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs-JLD1-PEI was also able to be transported to the brain and improved the functional deterioration in the HD

In this work, we present high-performance surface plasmonic sensors using gold nanostructures and Bragg photonic structures. The gold film on the Bragg structure provides Tamm plasmon states (TPs). The Fano coupling between higher order TPs and Bloch-wave surface plasmon polariton (BW-SPP) on the gold nanoslit array results in a new hybrid Tamm-plasmon mode. Using finite-difference time-domain calculations, we demonstrate that the hybrid mode has the advantages of high surface sensitivity of BW-SPP mode and high resonant quality of Tamm state. The calculated plasmonic field distribution shows that the hybrid mode has a similar evanescent distribution with BW-SPP mode on gold surface and TPs field in the Bragg structure. The experimental results verify that the hybrid mode has one hundred times higher wavelength sensitivity than the Tamm state. The figure of merit of the hybrid mode is five times better than the BW-SPP mode in conventional nanoslit arrays. The real-time sensorgram further confirms that the hybrid mode has a much higher sensitivity and better signal to noise ratios in the biomolecular interaction measurement.

We propose a measurement method for sensitive and label-free detections of virus-like particles (VLPs) using color images of nanoplasmonic sensing chips. The nanoplasmonic chip consists of 5×5 gold nanoslit arrays and the gold surface is modified with specific antibodies for spike protein. The resonant wavelength of the 430-nm-period gold nanoslit arrays underwater environment is about 570 nm which falls between the green and red bands of the color CCD. The captured VLPs by the specific antibodies shift the plasmonic resonance of the gold nanoslits. It results in an increased brightness of green pixels and decreased brightness of red pixels. The image contrast signals of (green - red) / (red + green) show good linearity with the surface particle density. The experimental tests show the image contrast method can detect 100-nm polystyrene particles with a surface density smaller than 2 particles/µm2. We demonstrate the application for direct detection of SARS-CoV-2 VLPs using a simple scanner platform. A detection limit smaller than 1 pg/mL with a detection time less than 30 minutes can be achieved.

We present the use of surface charges in dual gold-nanoslit electrodes to improve the surface plasmon resonance (SPR) detection limit by several orders of magnitude. The SPR is directly generated by gold-nanoslit arrays in the two electrodes. The SPR shifts for both nanoslit arrays are measured simultaneously with a simple hyperspectral setup. When biomolecules are captured by specific antibodies on the dual electrodes, the surface charge is changed during the electrochemical process due to the increase in surface impedance. The push-pull-type electrodes generate opposite surface charges. Using the differences in both spectral shifts, the change in surface charge is detected sensitively. We demonstrate that using a [Fe(CN)

This work presents a sensitive handheld refractometer using a tapered fiber tip, a multimode fiber, and a tiny mirror. The taper fiber tip was made using a modified wet etching method. The angular intensity distribution of the transmission light from the tapered fiber is sensitive to the refractive index of the surrounding solution. The low angular wave was reflected and collected by a multimode fiber. By setting a small collection angle and 10-mm distance between the fibers and the mirror, the maximum intensity sensitivity reaches up to 7.8 × 105%/RIU (refractive index unit). The sensor resolution of the sensor probe can achieve 8.7 × 10−5 RIU under 0.25% laser intensity stability. The simple handheld refractometer can be used to determine the properties of various liquids. For the glucose solution measurement under handheld condition, 0 to 50 °Bx can be distinguished by monitoring the intensity change. Considering the hand vibration and environmental disturbance, the sensor resolution was 1.22 °Bx.

A tapered fiber sensor was developed to detect the presence of condensed water and frost. The rough surface of the tapered fiber efficiently scattered the light propagating through the tapered fiber. The scattering loss is selective to the medium surrounding the tapered region of the fiber. Compared to the transmission intensity in the air, liquid water on the tapered fiber causes a 40% increase in transmission, whereas the presence of frost decreases the light transmission by 15%. Frost induces roughness on the surface of the tapered fiber and as a result increases light scattering and transmission losses. In contrast, liquid water uniformly covers the tapered fiber surface and reduces the light scattering. Furthermore, the amount of frozen water on the tapered surface is related to the duration of the transmission intensity peak during the defrosting process. The proposed detection scheme based on a rough tapered fiber can be utilized in real-time remote monitoring systems of the frost formation in large refrigeration systems.

The surface plasmon resonance (SPR)-based sensor has been widely used for biodetection. One of the attractive roles is the gold nanostructure with Fano resonance. Its sharp resonant profile takes advantage of the high figure of merit (FoM) in high-sensitivity detection. However, it is still difficult to detect small molecules at low concentrations due to the extremely low refractive index changes on the metallic surface. We propose using the coupling of image dipoles of gold nanoparticles (AuNPs) and Fano resonance of periodic capped gold nanoslits (CGNs) for sensitive small-molecule detections. The coupling mechanism was verified by three-dimensional finite-difference time-domain calculations and experiments. AuNPs on CGN form image dimer assemblies and induce image dipole with resonance wavelengths ranging from 730 to 550 nm. The surface plasmon polaritons (SPPs) interact with the image dipole of the AuNP on the CGNs and then scatter out through the periodic gold caps. The experimental results show that the peak intensity of grating resonance is decreased by the effect of image dipole and exhibits the maximum intensity change when the Fano resonance matches the resonance of image dipole. The 50 nm AuNPs can be detected with a surface density of less than one particle/μm

COVID-19 has shown that a highly specific and rapid diagnostic system is a necessity. A spectral imaging-based surface plasmon resonance (SPRi) platform with an integrated microfluidic biosensor to detect oligonucleotide sequences has been proposed to be a promising alternative for infectious diseases due to its safe and straightforward use. Approaches to reduce the DNA probe loading onto gold nanoparticles with various types of polyethylene glycol (PEG) were explored. Here, we demonstrated the stability of functionalised gold nanoparticles with unmodified PEG whilst lowering the probe loading density. The system was evaluated by performing the detection of a mimicking COVID-19 target sequence, single point-mutation sequence and fully mismatch sequence. Highly specific binding of the mimicking COVID-19 target sequence was observed and analysed by the spectral imaging SPR approach. Our work has demonstrated the potential of a controlled probe density using unmodified PEG as an especially promising functionalisation strategy in SPR spectral imaging assays.

Surface plasmon resonance (SPR) is an important technique for real-time and label-free detection of specific binding biomolecules. However, conventional SPR signals come from both the surface binding biomolecules and the variation in the bulk refractive index. This work demonstrates that Fano resonance in an aluminum capped nanoslit array has the ability to remove the signal of bulk refractive index changes from the SPR signal. As compared to gold nanostructures, the aluminum nanostructure provides an asymmetrical Fano resonance with clear peak and dip wavelengths. The peak wavelength is close to the grating resonance condition. The evanescent depth at the peak wavelength is up to several microns. The dip wavelength comes from the SPR effect. The evanescent depth at the dip wavelength is about 300 nm. By simultaneously measuring the shifts of peaks and the dip wavelengths, the variation in the bulk refractive index can be removed and only the biolayer thickness is measured. The finite-difference time-domain calculation shows that the 470 nm-period nanoslit array with 90 and 70 nm slit depths has the optimal thickness sensitivity. In this experiment, a simple multispectral imaging system is developed for multiple bio-interaction measurements. The measured results verify that the bulk refractive index changes can be removed and the surface biomolecular interactions can be directly obtained without the need of a reference channel.

Metastasis is a frequent complication of cancer and accounts for more than 60% of patients' mortality. Despite technological advancements, treatment options are still limited. Ion channels participate in the regulation of cell adhesion, whilst the regulation of cell adhesion further controls metastasis formation. However, to develop a new ion channel inhibitor targeting metastasis takes tremendous effort and resources; therefore, drug repurposing is an emerging strategy in oncology. In previous studies, we have developed a metal-based nanoslit surface plasmon resonance (SPR) platform to examine the influence of drugs on the cell adhesion process. In this work, we developed a scanner-based cell adhesion kinetic examination (CAKE) system that is capable of monitoring the cell adhesion process by measuring color changes of SPR biosensors. The system's performance was demonstrated by screening the anti-metastasis ability of compounds from a commercial ion-channel inhibitor library. Out of the 274 compounds from the inhibitor library, zinc pyrithione (ZPT) and terfenadine were demonstrated to influence CL1-5 cell adhesion. The cell responses to the two compounds were then compared with those by traditional cell adhesion assays where similar behavior was observed. Further investigation of the two compounds using wound healing and transwell assays was performed and inhibitions of both cell migration and invasion by the two compounds were also observed. The results indicate that ZPT and terfenadine are potential candidates for anti-metastasis drugs. Our work has demonstrated the label-free drug screening ability of our CAKE system for finding potential drugs for cancer treatment.

High-throughput and dynamic measurement for living cell activities can benefit biological research and drug development. A low-cost metallic nanostructure-based surface plasmon resonance (SPR) imaging platform, comprising multiple aluminum nanoslit arrays and a color image device, is proposed for label-free study of cell and drug interactions. The multiple nanoslit sensing arrays were fabricated using the compression-injection molding process. These sensing chips showed a detectable depth of 600 nm and refractive index resolution of ∼5 × 10-5 refractive index unit (RIU) by using a self-referenced two-color analysis. Two examples of kinetic studies of living cells under various doses of drugs are presented. The focal adhesion kinases inhibitor (FAKi 14) and cell interactions show exponential changes of cellular adhesion and time constants for different concentrations of antiadhesion drugs. The anticancer drug (doxorubicin (DOX))-treated cells show slow increases of SPR signals in the first 2 h due to the nucleus swelling. The DOX-treated cells further process plasma membrane disruption and become floating cells and debris in the medium, resulting in rapid drops of the SPR signals.

Surface plasmon resonance (SPR) nanowire array chips with a microfluidic system are an effective detection method for a rapid test device. This study investigated a capped gold nanowire array and a microfluidic test platform to provide a fundamental understanding of the kinetic binding of SPR nanowires and the surface gold refractive index. The device sensitivity of the SPR nanowire array was 485 nm RIU-1 and the detection limit was 4.1 × 10-5 RIU. Moreover, a kinetic binding analysis also indicated that a peak shift resulted from a specific hybridization of the target molecule with the immobilized probe on the gold nanostructures. The peak shift (red-shift) value of latent membrane protein 1 (LMP1) DNA was 2.21 nm. The results demonstrated that this new method had high sensitivity to detect amplified DNA products without labeling or complex sample treatment. The SPR nanowire chip can detect the PCR products at lower cycle numbers compared to gel electrophoresis due to probe and DNA specificity. Furthermore, the mechanisms of SPR nanowire array fabrication and the detection of the LMP1 gene were studied. The findings can assist in improving the biosensing of DNA-amplified products and in developing rapid detection devices with a small-footprint nanostructured SPR chip.

A compact imaging smartphone spectrometer utilizing a lightweight aspheric concave blazed-grating is presented for multichannel spectral detection. The lightweight concave diffraction grating is fabricated on a plastic substrate using a two-step thermal-embossing method in a cost-effective and mass-productive way, which enables a large-area, smooth and aspheric concave surface while preserving a blazed-grating structure. The blazed-grating serves as a key single element for aberration-free light focusing and highly-efficient light diffraction. It thus eliminates extra moving optics in the spectrometer and improves the optical characteristics and system integration, which are proven by both simulation and experiments. Spectral linewidth of 1 nm is achieved by combining the concave grating with a smartphone camera. This compact imaging smartphone spectrometer is only about the size of a match-box. Spectra can be obtained directly from the detected images using a developed application (APP) interface. High-throughput plasmonic resonance sensing using microfluidic silver nanoslit arrays under various glycerin environments is demonstrated, and the detected resonance wavelength response is comparable with that detected by a commercial compact spectrometer.

Nanostructure-based surface plasmon resonance biosensors have attracted considerable attention since the phenomenon of extraordinary light transmission in metallic nanohole arrays was discovered. However, the mass production of uniform metallic nanostructures with a low-cost, rapid, and high-throughput fabrication process remains a key issue for various multiplex sensing applications. We successfully utilized injection compression molding to mass fabricate transmission-type Fano resonance biochips with a feature size of 60 nm for multiplex sensing applications. Two types of metallic nanostructures, aluminum nanoslits and capped aluminum nanoslits with 24 sensing arrays, were made on polycarbonate substrates. The bulk sensitivity and uniformity of the nanostructure arrays were tested. A Fano resonance with a full-width at half-maximum bandwidth of 8 nm was observed in the visible light region for 470-nm-period capped aluminum nanoslit arrays. The refractive index sensitivity was 460 nm/RIU, and a figure of merit of 58 was achieved. Moreover, aluminum nanoslits had a dip resonance with a bandwidth of 25 nm and a refractive index sensitivity of 463 nm/RIU. The coefficients of variation of the refractive index sensitivities for 24 arrays on a biochip and 10 biochips from different fabrication batches were both below 3%, which indicates that uniform nanostructures can be fabricated by injection compression molding and that the reproducibility is controllable. In addition, the multiplex sensing capability of the aluminum nanostructure arrays was demonstrated by simultaneously monitoring 24 water/glycerin solutions with a hyperspectral imaging system. Protein–protein interactions between bovine serum albumin and anti-bovine serum albumin demonstrated proof of concept of the biological detection capability of the chips. To benefit various multiplex sensing applications such as clinical disease diagnosis, drug screening, and protein biomarker discovery, 96-array aluminum nanoslit biochips the same size as a standard 96-well plate were successfully fabricated. Such a nanostructure-based plasmonic biochip produced by a low-cost, rapid, and high-throughput fabrication method can benefit commercial applications.

Background: Gold nanoparticles (AuNPs) have been widely used as local surface plasmon resonance (LSPR) immunoassay for biomolecule sensings. It is primarily based on two conventional methods - absorption spectra and colorimetric. While the low figure of merit (FoM) of the LSPR and high-concentration AuNPs requirement restrict their limit of detection (LOD), which is around ng to μg per mL in antibody detection if there is no other signal or analytes amplification. By now, the improvement of sensitivity has bogged down for years. It also reveals a great challenge of the current LSPR immunoassay in biosensing - pushing the boundary of the current LOD.Results: In this work, we developed a spectral image contrast-based flow digital nanoplasmon-metry(FDNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the signal of peak shift is extremely amplified and quickly detected. Introducing the digital analysis, the FDNM provides an ultra-high signal-to-noise ratio and less sample volume requirement. Compared to conventional analog LSPR immunoassay, FDNM has a LOD down to 1 pg mL-1 within only a 15-minute detection time and 500 μL sample volume. Antibody against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins was also conducted to validate the detection of FDNM in complicated samples. Of the detection, FDNM shows significant discrimination with a LOD of 10 pg mL-1 and a broad dynamic detecting range of five orders of magnitude. Conclusion: Together with the quick readout time and simple operation, this work outstandingly demonstrated the high sensitivity and selectivity of the developed FDNM in rapid antibody detection. The spectral image contrast and digital analysis further provide a new generation LSPR immunoassay of AuNPs.

Background Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to μg mL−1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. Results In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL−1 within only a 15-min detection time and 500 μL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL−1 and a broad dynamic detection range of five orders of magnitude. Conclusion Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs. Graphical Abstract

A variety of physiological and pathological processes rely on cell adhesion, which is most often tracked by changes in cellular morphology. We previously reported a novel gold nanoslit-based biosensor that is capable of real-time and label-free monitoring of cell morphological changes and cell viability. However, the preparation of gold biosensors is inefficient, complicated and costly. Recently, nanostructure-based aluminum (Al) sensors have been introduced for biosensing applications. The Al-based sensor has a longer decay length and is capable of analyzing large-sized mass such as cells. Here, we developed two types of double-layer Al nanoslit-based plasmonic biosensors, which were nanofabricated and used to evaluate the correlation between metastatic potency and adhesion of lung cancer and melanoma cell lines. Cell adhesion was determined by Fano resonance signals that were induced by binding of the cells to the nanoslit. The peak and dip of the Fano resonance spectrum respectively reflected long- and short-range cellular changes, allowing us to simultaneously detect and distinguish between focal adhesion and cell spreading. Also, the Al nanoslit-based biosensor chips were used to evaluate the inhibitory effects of drugs on cancer cell spreading. We are the first to report the use of double layer Al nanoslit-based biosensors for detection of cell behavior, and such devices may become powerful tools for anti-metastasis drug screening in the future.

Surface plasmon resonance imaging (SPRi) is capable of real-time, label-free, and high-throughput detection for many sensing applications. The conventional prism-based SPRi system is operated with ...

A simple design for shifting the resonance wavelength of silver nanoslits using an electrowetting-on-dielectric (EWOD) cell is proposed. The EWOD cell comprises a polycarbonate (PC) substrate with Teflon-coated silver nanoslits and a glass substrate with Teflon-coated electrodes. A glycerol droplet is placed between the two substrates, and out of the path of a probe beam at zero electric field. Application of an electric field smaller than 0.3 V/µm on the electrodes moves the glycerol droplet into the path of the probe beam, shifting the resonance wavelength of the silver nanoslits by 135 nm. A change (0.33) in the refractive index of the effective medium that is adjacent to the silver nanoslits causes a large shift in the resonance wavelength. The spectral shift of the silver nanoslits is repeatable by the electric field. This simple design is a great achievement for high-performance electro-optical devices with large wavelength shift ranges such as optical switches, variable optical attenuators, and sensor applications.

Compared to conventional surface plasmon resonance (SPR) biosensor using a prism coupler, the metallic nanostructure-based plasmonic sensor takes advantage of high-throughput and on-chip detections.

In recent years, imidacloprid and fipronil have been reported to harm beneficial insects, such as honey bees, and to potentially pose risks to mammals, including humans. Considering their widespread use and potential minimum toxic range from 10 ppb to 1 ppm (species dependent), a simple, rapid, sensitive, and reliable method for screening and detection is urgently needed. Here, we present a surface plasmon resonance (SPR)-based nanoplasmonic chip integrated with a multichannel spectral imaging system to detect ecosystem-harming pesticides. The pre-modification of the designed mercapto-haptens reduced detection time to 2.5 h. Moreover, owing to the multichannel configuration, it was possible to introduce an internal standard analytical method to effectively reduce matrix interference in real samples; thus, the concentration of the target pesticide could be determined more precisely. The strong linearity of the spiked sample test results indicated high accuracy in quantifying target pesticides. Considering the limit of detection (~10 ppb), the cutoffs for detection and quantification were set at 15 and 45 ppb, respectively, and were used as the detection criteria. The detection results of the blind tests of real samples were also compared with those of liquid chromatography electrospray ionization tandem mass spectrometry (standard method) and were highly consistent. The custom-made integrated SPR system allows much simpler, label-free, high-throughput, and reliable on-site identification and quantification of imidacloprid and fipronil. All test results validated the platform's capability in the on-site rapid screening and detection of pesticide residues at the parts per billion and parts per million levels.

A sensitive tapered optical fiber tip combined with dielectrophoretic (DEP) trapping was used for rapid and label-free detection of bacteria in water. The angular spectrum of the optical field at the fiber tip was changed with the surrounding refractive index (RI). By measuring far-field intensity change at the defocus plane, the intensity sensitivity was up to 95 200%/RIU (RI unit), and the detection limit was 5.2 × 10–6 RIU at 0.5% intensity stability. By applying an AC voltage to a Ti/Al coated fiber tip and an indium–tin-oxide glass, the DEP force effectively trapped the Escherichia coli (E. coli) near the fiber tip. Those bacteria can be directly measured from optical intensity change due to the increase of surrounding RI. By immobilizing the antibody on the Ti/Al fiber tip, the tests for specific K12 bacteria and nonspecific BL21 bacteria verified the specificity. The antibody-immobilized Ti/Al coated fiber tip with DEP trapping can detect bacteria at a concentration about 100 CFU/mL.

Controlling circularly polarized (CP) states of light is critical to the development of functional devices for key and emerging applications such as display technology and quantum communication, and the compact circular polarization-tunable photon source is one critical element to realize the applications in the chip-scale integrated system. The atomic layers of transition metal dichalcogenides (TMDCs) exhibit intrinsic CP emissions and are potential chiroptical materials for ultrathin CP photon sources. In this work, we demonstrated CP photon sources of TMDCs with device thicknesses approximately 50 nm. CP photoluminescence from the atomic layers of tungsten diselenide (WSe2) was precisely controlled with chiral metamolecules (MMs), and the optical chirality of WSe2 was enhanced more than 4 times by integrating with the MMs. Both the enhanced and reversed circular dichroisms had been achieved. Through integrations of the novel gain material and plasmonic structure which are both low-dimensional, a compac...

We present a design method and fabrication technique for enhancing detection sensitivity of gold nanostructure-based surface plasmon resonance (SPR) biosensors. In this case, the nanostructure geometry is arbitrary and the optimal design parameters are determined using a microgenetic algorithm integrated with three-dimensional finite-difference time-domain (3D-FDTD) electromagnetic simulations. The corresponding device is fabricated using hot embossing nanoimprint lithography. Two experimental configurations are used to evaluate the device performance: one is the atomic layer deposition and the other is the protein–protein interaction. The performances of the optimal SPR biosensors are superior to the ones with conventional simple structures under both configurations. The improvements in terms of the fitness function are respectively up to 179% and 128% for the 3D-FDTD simulation and the experimental results. The calculated optical fields indicate that the improvement of the fitness function results from ...

Plasmonic hot-carriers, which are induced by plasmons at metal surfaces, can be used to convert photon energy into excited carriers over a subwavelength region and provide a new means to realize photodetection within the sub-band-gap region of semiconductor materials. However, the barrier height of the metal–semiconductor junction affects the behavior of the plasmon-induced hot-carriers and limits the electrical response of photodetection. High electrical responsivity, achieved by manipulating the barrier height using plasmon-induced hot electrons, is desired to broaden the possible applications. Here we report a plasmonic channel-coupled nanogap structure, where the barrier height of the metal–semiconductor junction is altered upon the excitation of plasmon-induced hot-carriers. The structure consists of semiconductor channels and metal slabs forming nanogaps, which sustain coupled plasmons and confine light to the semiconductor–metal interfaces. In contrast to conventional Schottky barriers and ohmic co...

The clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs could potentially provide useful information for monitoring disease progression, prompting definitive treatment decisions. In the past decade, advancements in biosensing technology have led to a shift towards rapid, real-time and label-free detection systems; as such, surface plasmon resonance (SPR) biosensor-based technology has become of high interest. Here, we developed an automated multiplex transmissive surface plasmon resonance (t-SPR) platform with the use of a capped gold nanoslit integrated microfluidic surface plasmon resonance (SPR) biosensor. The automated platform was custom designed to allow the analysis of spectral measurements using wavelength shift (dλ), intensity (dI) and novel area change (dA) for surface binding reactions. A simple and compact nanostructure based biosensor was fabricated with multiplex real-time detection capabilities. The sensitivity and specificity of the microfluidic device was demonstrated through the use of functionalised AuNPs for target molecule isolation and signal enhancement in combination with probes on the CG nanoslit surface. Our work allows for the multiplex detection of miRNA at femtomolar concentrations in complex media such as urine.

We developed dielectric heating-assisted nanoimprint method for rapid fabrication of ultraflexible nanostructures. Using spin-coating polyvinyl-chloride (PVC) film on the glass slide, the dielectric heating on PVC film helped the pattern transfer from the mold to PVC film in few seconds. Various kinds of nanostructures were successfully made on PVC films with about 20-μm thickness. We demonstrated the applications of ultraflexible metallic nanostructures for bending measurement using surface plasmon resonance (SPR) and surface enhanced Raman scattering (SERS) on the curved surfaces. For measuring bending angles using SPR on capped nanowire arrays, the minimum detection angle was 2.4 × 10−3 degree under 0.02 nm wavelength resolution. For SERS measurement, the nanorod arrays on a curved substrate can increase SERS signals for two times as compared to planar SERS substrate.

An osmium-coated lensed fiber (OLF) probe combined with a silver-coated black silicon (SBS) substrate was used to generate a dielectrophoretic (DEP) force that traps bacteria and enables Raman signal detection from bacteria. The lensed fiber coated with a 2-nm osmium layer was used as an electrode for the DEP force and also as a lens to excite Raman signals. The black silicon coated with a 150-nm silver layer was used both as the surface-enhanced Raman scattering (SERS) substrate and the counter electrode. The enhanced Raman signal was collected by the same OLF probe and further analyzed with a spectrometer. For Raman measurements, a drop of bacterial suspension was placed between the OLF probe and the SBS substrate. By controlling the frequency of an AC voltage on the OLF probe and SBS substrate, a DEP force at 1 MHz concentrated bacteria on the SBS surface and removed the unbound micro-objects in the solution at 1 kHz. A bacteria concentration of 6 × 104 CFU/mL (colony forming units per mL) could be identified in less than 15 min, using a volume of only 1 μL, by recording the variation of the Raman peak at 740 cm−1.

In this study, a multiplex detection system was proposed by integrating a localized surface plasmon resonance (LSPR) sensing array and parallel microfluidic channels. The LSPR sensing array was fabricated by nanoimprinting and gold sputter on a polycarbonate (PC) substrate. The polydimethylsiloxane (PDMS) microfluidic channels and PC LSPR sensing array were bound together through (3-aminopropyl)triethoxysilane (APTES) surface treatment and oxygen plasma treatment. The resonant spectrum of the LSPR sensing device was obtained by broadband white-light illumination and polarized wavelength measurements with a spectrometer. The sensitivity of the LSPR sensing device was measured using various ratios of glycerol to water solutions with different refractive indices. Multiplex detection was demonstrated using human immunoglobulin G (IgG), IgA, and IgM. The anti-IgG, anti-IgA, and anti-IgM were separately modified in each sensing region. Various concentrations of human IgG, IgA, and IgM were prepared to prove the concept that the parallel sensing device can be used to detect different targets.

The studies of nanostructure-based aluminum sensors have attracted huge attention because aluminum is a more cost-effective plasmonic material. However, the intrinsic properties of the aluminum metal, having a large imaginary part of the dielectric function and a longer electromagnetic field decay length and problems of poor long-term chemical stability, limit the surface-sensing capability and applicability of nanostructures. We propose the combination of capped aluminum nanoslits and a thin-capped dielectric layer to overcome these limitations. We show that the dielectric layer can positively enhance the wavelength sensitivities of the Wood's anomaly-dominant resonance and asymmetric Fano resonance in capped aluminum nanoslits. The maximum improvement can be reached by a factor of 3.5. Besides, there is an optimal layer thickness for the surface sensitivity because of the trade-off relationship between the refractive index sensitivity and decay length. We attribute the enhanced surface sensitivity to a reduced evanescent length, which is confirmed by the finite difference time-domain calculations. The protein-protein interaction experiments verify the high-surface sensitivity of the structures, and a limit of quantification (LOQ) of 1 pg/mL anti-bovine serum albumin is achieved. Such low-cost, highly sensitive aluminum-based nanostructures can benefit various sensing applications.

A chip-based ultrasensitive surface plasmon resonance (SPR) sensor in a checkerboard nanostructure on plastic substrates is presented for digital detection. The sensing elements on the checkerboard are composed of silver-capped nanoslit arrays, which were fabricated using the thermal-embossing nanoimprint method, to meet the demand for low-cost and rapid fabrication. Sharp Fano resonances in the optimized nanoslit arrays provide high-intensity sensitivities (20,000% per refractive index unit), with an element size of 12.5µm. The polarization-dependent transmission in the checkerboard pattern produces optical isolation between sensing elements and results in a crosstalk lower than 1%. Protein-antibody experiments demonstrated that the digital detection limit was up to 1pg/mL, which is approximately 1000 times lower than that of conventional analog detection. For a 140µm×140µm checkerboard pattern, the dynamic range was approximately 100 times higher than that of conventional surface plasmon resonance measurements. This new digital detection method is very useful for detecting ultralow concentrations of analytes with a nonuniform distribution on the sensor surface.

We presented a surface plasmon resonance (SPR) sensor with an angular sensitivity up to 440 deg/RIU by using (±1,∓1) mode on a hexagonal gold nanohole array. The large-area gold nanohole arrays were fabricated by thermal-annealing template-stripping method with 180-nm-hole diameter and 600-nm period. A flat dispersion curve deviated from Bragg condition for (±1,∓1) mode occurred when incident angle was larger than 20°. The finite-difference time-domain calculations verified that plasmonic mode changed from surface plasmon mode to cavity mode in nanoholes. Such mode transition resulted in the large change of dispersion curve. The angular sensitivity of the (±1,∓1) mode near the transition band was 6.2 times higher than surface plasmon mode under Bragg condition and 4.5 times higher than prism-based SPR sensors at 850 nm wavelength. Biosensing experiments for antigen-antibody interactions verified the surface binding sensitivity was higher than prism-based SPR machine.