Liquid Analytes Research Articles

Cucurbit[n]uril-Immobilized Sensor Arrays for Indicator-Displacement Assays of Small Bioactive Metabolites

The patterned immobilization of chemosensors into nano-/microarrays has often boosted application in diagnostics and environmental sensing applications. While this is a standard approach for biosensors, e.g. with antibodies, other proteins and DNA, arraying is not yet adopted widely for supramolecular chemosensors which are still predominantly used in solution systems. Here we introduce the patterned immobilization of cucurbit[n]urils (CBn).[1, 2] into multiplexed microarrays and elucidate their prospects for advancement of surface-bound indicator-displacement assays (IDA) to detect small molecule analytes.[3, 4] The microarrays were generated by microchannel cantilever spotting (µCS) of functionalized CBn and subsequent self-assembly of corresponding indicator dyes from solution. Enhanced sensitivity of surface-bound microarrays was established in demonstrations with small bioactive metabolites (spermine, amantadine, and cadaverine) compared to bulk assays. Furthermore, integration of the CBn/indicator microarrays into microfluidic channels provides an efficient way for real-time monitoring of the sensing process, allows easier handling and reduces need in analyte volume. The concept was further extended to differential sensing of analytes on diplex or multiplex CBn/indicator microarrays, opening-up a route to multi-component sensing of small molecule analytes in complex liquids.[5] [1] F. Biedermann and W. M. Nau, Angew. Chem. Int. Ed., 2014, 53 (22), 5694-5699 [2] C. Hu, L. Grimm, A. Prabodh, A. Baksi, A. Siennicka, P. A. Levkin, M. M. Kappes and F. Biedermann, Chem. Sci., 2020, 11, 11142 [3] J. Atwater, D. S. Mattes, B. Streit, C. B.‐Kninski, F. F. Loeffler, F. Breitling, H. Fuchs and M. Hirtz, Adv. Mater., 2018, 30, 1801632 [4] S. M. M. Dadfar, S. Sekula‐Neuner, U. Bog, V. Trouillet and M. Hirtz, Small, 2018, 14 (21), 1800131 [5] C. Zhong, C. Hu, R. Kumar, V. Trouillet, F. Biedermann and M. Hirtz, ACS Appl. Nano Mater., 2021

A highly sensitive quadruple D-shaped open channel photonic crystal fiber plasmonic sensor: A comparative study on materials effect

A highly sensitive dual-polarized 'X' oriented quadruple D-shaped open channel photonic crystal fiber (PCF) based surface plasmon resonance (SPR) sensor for various analyte detection is proposed in this paper. Gold is taken as a plasmonic material for its stability and compatibility. Silicon nitride (Si3N4) and titanium oxide (TiO2) has been used separately as an adhesive layer of gold to elevate the sustainability of the evanescent field. This paper shows a comparative study and inspects the effect of sensing performance between Si3N4 and TiO2 as an adhesive layer of gold. Numerical investigations have been followed up using the finite element method (FEM). For practical feasibility, analyte and plasmonic materials have been placed at the outer surface of the sensor. After watchful investigation, the maximum wavelength sensitivities of 21,000 nm/RIU (Refractive Index Unit) and 18,000 nm/RIU have been found for the y-polarization when using TiO2 and Si3N4, respectively. The highest amplitude sensitivities are of 914RIU−1 and 625RIU−1 for TiO2 and Si3N4, respectively. Furthermore, minimum wavelength resolutions of 4.76 × 10−6 RIU and 5.55 × 10−6 RIU have been observed in y-polarization for TiO2 and Si3N4, respectively. The sensor evinces a maximum figure of merit (FOM) of 236RIU−1 for TiO2. This sensor has the analyte sensing range of 1.31–1.38RI (Refractive Index) for TiO2 and 1.32–1.39RI for Si3N4. The sensor also delivers low confinement loss for Si3N4 and TiO2, which certifies viability in fabricating the design. Recognizing this sensor’s wavelength sensitivity, amplitude sensitivity, and sensing RI range, it could be a promising candidate for detecting different liquid analytes with excellent accuracy.

Smartphone-based colorimetric sensor application for measuring biochemical material concentration

In this paper, colorimetric analysis for biochemical samples has been realized, by developing an easy-to-use smartphone colorimetric sensing android application that can measure the molar concentration of the biochemical liquid analyte. The designed application can be used for on-site testing and measurement. We examined three different biochemical materials with the application after preparation with five different concentrations and testing in laboratory settings, namely glucose, triglycerides, and urea. Our results showed that for glucose triglycerides, and urea the absorbance and transmittance regression coefficient (R2) for the colorimetric sensing application were 0.9825, and 0.9899; 0.9405 and 0.9502; 0.9431 and 0.8597, respectively. While for the spectrophotometer measurement the (R2) values were 0.9973 @560 nm and 0.9793 @600 nm; 0.952 @620 nm and 0.9364 @410 nm; 0.9948 @570 nm and 0.9827 @530 nm, respectively. The novelty of our study lies in the accurate prediction of multiple biochemical materials concentrations in various lightning effects, reducing the measurement time in an easy-to-use portable environment without the need for internet access, also tackling various issues that arise in the traditional measurements like power consumption, heating, and calibration. The ability to convey multiple tasks, prediction of concentration, measurement of both absorbance and transmittance, with error estimation charts and (R2) values reporting within the colorimetric sensing application as far as our knowledge there has not been any application that can provide all the capabilities of our application.

Abstract PS6-60: A clustering and mutual information based analysis of the ELIMA study results: The additive value of multi-parametric liquid biopsies, including CTCs, EVs and cfDNA, in metastatic breast cancer

Abstract Background: To gain comprehensive insights into the aspects of genomic and transcriptomic complexity which could be beneficial for therapy management in metastatic breast cancer (MBC), we established the isolation and analysis of mRNA and gDNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) from a minimized blood volume. Here, we aimed to assemble the results of all four analytes and elucidated the relevance of the diverse parameters within a multimodal data set. Methods: EDTA blood (2x 9 ml) was drawn from 26 MBC patients with hormone receptor-positive and HER2 negative primary tumors at the time of disease progression. CTCs and their mRNA were isolated using the AdnaTest EMT2/StemCell Select/Detect. Plasma of CTC-depleted blood was used for cfDNA isolation, while mRNA from EVs was isolated by exoRNeasy using the remaining blood. The mRNA purified from CTCs and EVs was analyzed by a multimarker qPCR panel. gDNA from CTCs was isolated from the mRNA-depleted CTC lysates using the AllPrep DNA/RNA Nano Kit prototype. CTC gDNA and cfDNA were analyzed with a customized QIAseq Targeted DNA Panel for Illumina with unique molecular indices. Consumables: QIAGEN, Germany. The statistical tools for evaluating the results included: Hierarchical clustering according to Ward’s method with Euclidean distance, singular value decomposition, mutual information calculation, and k-means clustering. Results: Isolation of mRNA and gDNA from CTCs, mRNA from EVs, and cfDNA was successfully established in a condensed workflow. 88% of the patients showed at least one variant in CTC gDNA or one overexpression signal in the CTC mRNA fraction. The mean number of variants/signals was also higher in CTC gDNA/mRNA when compared to cfDNA/EV mRNA. The analysis of individual analytes identified a similar number of patients (50%-73%) with actionable markers, but a multi-parametric evaluation of all four analytes identified actionable markers in 96% of the patients. After hierarchical clustering of the results of each individual analyte into four clusters, combining the two patient clusters with the worst overall survival resulted in prognostic value for CTC gDNA, cfDNA, and EV mRNA. Combination of the information above analyte borders showed additive value and resulted in a prognostic factor defined here as the ‘ELIMA score’. A calculation of the mutual information showed that CTC gDNA has the highest potential to describe the other three analytes. However, an Eigenvector analysis based on singular value decomposition revealed that the 10 most influential vectors contain parameters from all four analytes. This indicates that each of the analytes add valuable information not conveyed by the other analytes. K-means clustering was used to generate clusters based solely on CTC gDNA and based on all four analytes. A comparison of the clusters based on these two criteria showed that clustering based on all four analytes resulted in a division of patients according to their tumor histology type and ERBB2 variants in CTCs; thereby, underscoring the importance of taking all four analytes into consideration. Conclusion: We established a workflow for parallel isolation of multiple liquid biopsy analytes from a minimized blood volume. Though the mutual information calculation showed that CTC gDNA has a relatively greater ability to describe the other three analytes, further statistical analysis showed that each analyte carried information of additive value. Thus, a comprehensive picture of the genomic and transcriptomic complexity obtained by a multi-parametric liquid biopsy might enable easier identification of the most suitable therapy regimen for each individual patient in the future. Citation Format: Sabine Kasimir-Bauer, Vinay Suryaprakash, Markus Storbeck, Peter Hahn, Siegfried Hauch, Markus Sprenger-Haussels, Oliver Hoffmann, Rainer Kimmig, Corinna Keup. A clustering and mutual information based analysis of the ELIMA study results: The additive value of multi-parametric liquid biopsies, including CTCs, EVs and cfDNA, in metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-60.

High Sensitivity Core-Shell Structure (CSS)-Based Fiber Sensor for Monitoring Analytes in Liquids and Gases

A compact and robust mid-infrared refractive index-based microstructured fiber sensor with high sensitivity is developed for monitoring analytes in liquids and gases. Resonant core-shell elements facilitate its exceptional performance. The theory underpinning them is explained, and the evolution of the fiber structure is presented. The material choices and details of the microstructure leading to its optimization are described. Simulation results demonstrate that the optimized fiber sensor can readily detect refractive index variations in the range from 1.0 to 1.41 and that its wavelength sensitivities are 2510 and 4303 nm/RIU for analyte detection, respectively, in gases and liquids. It is an excellent candidate for environmental monitoring applications.

Glide-Symmetric Acoustic Waveguides for Extreme Sensing and Isolation

Glide symmetry offers new degrees of freedom to engineer the properties of periodic structures, and thus it has been exploited in various electromagnetic structures. However, so far there has been little exploration on the impact that glide symmetry can offer in the field of acoustics. In this paper, we explore glide-symmetric acoustic waveguides, highlighting their dispersion characteristics and guiding properties and demonstrating opportunities in the context of acoustic devices. Here we analytically derive their dispersive features applying a semi-analytical mode matching technique. We then demonstrate how the unusual dispersion properties of glide-symmetric acoustic waveguides can be used to achieve very sharp frequency responses. Based on these results, we propose a sensing platform for liquid analytes that exhibits large sensitivity and linearity. Furthermore, by introducing fluid motion, we leverage these responses to design an acoustic isolator based on acoustic Mach-Zehnder interferometry, whose design is more favorable in terms of footprint and complexity in comparison to other acoustic nonreciprocal devices that do not rely on glide symmetry.

Plasmonic Biosensor for Low-Index Liquid Analyte Detection Using Graphene-Assisted Photonic Crystal Fiber

We report a sensitive D-shaped photonic crystal fiber-based surface plasmon resonance (PCF-SPR) sensor with linear sensing performance and a broad detection range for low refractive index (RI) liquid analytes ranging from 1.27 to 1.37 with possible extension beyond this range. We examine three combinations of materials (silver only, graphite on silver, and graphene on silver) as plasmonic nanofilm for the PCF-SPR and demonstrate that graphene-assisted PCF has the best overall performance. We show that graphene coating of silver nanofilm improves the sensitivity and the overall figure of merit of the sensor, besides the practical benefit of protecting the silver nanofilm from surface oxidation. Furthermore, we propose two distinct ways of analyte sensing based on filling patterns where the liquid analyte can be filled internally into the top two air holes of the PCF, or externally into a rectangle channel at the top of the fiber. In the internal filling detection scheme, the graphene-assisted PCF-SPR sensor demonstrates ultra-linearity, a detection range of 0.1 refractive index unit (RIU) between 1.27 and 1.37, an average linear spectral sensitivity of 2320 nm/RIU, and a maximum amplitude sensitivity of 192 RIU−1 for 1150 nm excitation. In the external filling detection scheme, the PCF-SPR exhibits extremely large sensitivities with a maximum spectral sensitivity of 22,400 nm/RIU close to analyte RI of 1.33, and a maximum figure of merit (FOM) of 127 which is approximately five times larger than that of the similar reported PCF-SPR sensors in the literature. The combination of a broad detection range for low-index analytes, large sensitivities, design flexibility, and stability against surface oxidation renders our proposed sensor as an interesting candidate for biosensing applications in chemistry, biology, and medicine.

Development of capillary-paper spray for small-molecule analysis in complex samples.

We develop a capillary-paper spray (CPS) ion source which allows for sample separation in the capillary and enables rapid and sensitive paper spray (PS) mass spectrometry (MS) analysis of biofluids. The CPS employs a glass capillary to load liquid analytes, vertically standing at the rear of the PS. To further reduce the matrix effect, a nitrocellulose filter membrane is placed between the glass tube and chromatography paper to absorb proteins and other macromolecules, which is beneficial for the detection of the small molecules. Compared with the normal PS method, the CPS method markedly improves spray stability and prolongs analysis duration, and also generates significantly better signal intensities during the analysis of drugs, thus indicating its potential for clinical use. As a proof of concept, quantitative analysis of drugs (metformin hydrochloride and berberine hydrochloride) in serum is performed.

Quasi-D-Shaped Fiber Optic Plasmonic Biosensor for High-Index Analyte Detection

In this paper, we propose a highly sensitive quasi-D-shaped fiber optic biosensor for detection of high refractive index (RI) liquid analytes via surface plasmon resonance. The main mechanism of sensing is interplay between photonic crystal fiber fundamental mode and plasmonic mode which leads to formation of different resonance peaks depending on the analyte RI. We numerically analyze the structure sensitivity to design parameters and demonstrate the sensing performance of the proposed biosensor using both spectral sensitivity and amplitude sensitivity methods. The proposed biosensor has a RI detection range of 0.15 refractive index unit (RIU) from 1.45 to 1.6. The sensor exhibits linear sensing performance with a RI spectral sensitivity of 9300 nm/RIU for analyte RI ranging from 1.45 to 1.525, 1176 nm/RIU for analyte RI ranging from 1.525 to 1.6 and in particular, 11800 nm/RIU for analyte RI between 1.475 and 1.5. Furthermore, an average RI sensitivity of 4800 nm/RIU for analyte RI ranging from 1.45 to 1.6 is demonstrated. We also study the amplitude sensitivities of the proposed sensor which show promising maximum values of 183.6 RIU $^{-1}$ for 785 nm excitation and 820 RIU $^{-1}$ for 1050 nm excitation. Due to the simple structure of the proposed biosensor, large detection range, high sensitivity and promising linear sensing performance, the proposed biosensor can be a promising candidate for detecting various high RI chemical and biochemical samples.

A D-Shaped Photonic Crystal Fiber Refractive Index Sensor Coated with Graphene and Zinc Oxide.

A surface plasmon resonance (SPR) sensor based on a D-shaped photonic crystal fiber (PCF) with an uncomplicated structure is proposed to detect the change of refractive index of liquid analytes, and numerical simulation is carried out by the finite element method (FEM). Using silver as the plasmonic metal, the performances of the SPR-PCF sensor coated with a graphene layer and zinc oxide (ZnO) layer were assessed. The sensor designed is only coated with material on the polished surface, which makes the sensor production uncomplicated and solves the problems of filling material in the hole and coating on the hole wall. The effects of structural parameters such as graphene layer thickness, silver layer thickness, ZnO thickness, lattice spacing and manufacturing tolerance of blowhole diameter on the sensor performance were numerically simulated. The numerical results show that the sensitivity of the SPR-PCF sensor coated with 25 nm ZnO is highest in the ZnO thickness range from 10 to 25 nm. In the refractive index range of 1.37–1.41 for liquid analyte, the maximum sensitivity and corresponding resolution reach 6000 nm/RIU and 1.667 × 10−5, respectively. In addition, the sensor has good stability and high structural tolerance under the tolerance of ±5% of blowhole diameter. This work has wide application value in the detection of biochemical analytes, water pollution monitoring, food quality, and medical diagnosis.

Comparative Analysis of Highly Sensitive PCF for Chemical Sensing in THz Regime

Nowadays photonic crystal fiber (PCF) is used for sensing purposes in different fields. In this work, we have proposed a PCF based chemical (Benzene and Ethanol) sensor. Finite Element Method (FEM) based software COMSOL 5.3a is used to investigate the numerical characteristics for the proposed structure. From the numerical analysis, we obtained high sensitivity with low losses for an optimum core diameter of 210 µm. Our proposed PCF works on a broad range of core diameters and THz frequency spectra. The fabrication of this model is very simple due to its simplistic design structure. Full Text: PDF ReferencesMd.F.H. Arif, Md.J.H. Biddut, "A new structure of photonic crystal fiber with high sensitivity, high nonlinearity, high birefringence and low confinement loss for liquid analyte sensing applications", Sensing Bio-Sensing Res. 12, 8 (2017). CrossRef P. Kumar, Md.H. Bikash, K. Ahmed, S. Sen, "A Novel Hexahedron Photonic Crystal Fiber in Terahertz Propagation: Design and Analysis", Photonics 6(1), 32 (2019). CrossRef S. Asaduzzaman, K. Ahmed, T. Bhuiyan, T. Farah, "Hybrid photonic crystal fiber in chemical sensing", SpringerPlus 5, 748 (2016). CrossRef Md.S. Islam, J. Sultana, J. Atai, D. Abbott, S. Rana, M.R. Islam, "Ultra low-loss hybrid core porous fiber for broadband applications", App. Opt. 56(4), 1232 (2017). CrossRef S. Atakaramians, S. Afshar, H. Ebendorff-Heidepriem, M. Nagel, B.M. Fischer, D. Abbott, T.M. Monro, "THz porous fibers: design, fabrication and experimental characterization", Opt. Expr. 17(16), 14053 (2009). CrossRef

Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient.

Currently, clinical characterization of metastatic breast cancer is based on tissue samples taken at time of diagnosis. However, tissue biopsies are invasive and tumors are continuously evolving, which indicates the need for minimally invasive longitudinal assessment of the tumor. Blood-based liquid biopsies provide minimal invasive means for serial sampling over the course of treatment and the opportunity to adjust therapies based on molecular markers. Here, we aim to identify cellular changes that occur in breast cancer over the lifespan of an affected patient through single-cell proteomic and genomic analysis of longitudinally sampled solid and liquid biopsies. Three solid and 17 liquid biopsies from peripheral blood of an ER+/HER2− metastatic breast cancer patient collected over 4 years and eight treatment regimens were analyzed for morphology, protein expression, copy-number alterations, and single-nucleotide variations. Analysis of 563 single morphometrically similar circulating tumor cells (CTCs) and 13 cell-free DNA (cfDNA) samples along with biopsies of the primary and metastatic tumor revealed progressive genomic evolution away from the primary tumor profiles, along with changes in ER expression and the appearance of resistance mutations. Both the abundance and the genomic alterations of CTCs and cfDNA were highly correlated and consistent with genomic alterations in the tissue samples. We demonstrate that genomic evolution and acquisition of drug resistance can be detected in real time and at single-cell resolution through liquid biopsy analytes and highlight the utility of liquid biopsies to guide treatment decisions.

Hollow core photonic crystal fiber for chemicals sensing in liquid analytes: Design and analysis

In this paper, a hollow core photonic crystal fiber (PCF)-based THz chemicals sensor has been presented. Hexagonal shaped hollow core and symmetrical hexagonal air lattices have been used in the cladding section to construct the PCF geometry. The developed PCF-based chemical sensor yields high performance in ethanol, methanol, water and benzene detection in targeted liquid samples in the THz regime, which is nearly 99% at 3 THz. Additionally, it reveals very negligible losses in both polarization modes. In addition, it renders significant improvement in different sensing properties like effective area, effective refractive index, numerical aperture (NA), nonlinear coefficient, spot size and beam divergences because of strategic geometrical arrangements. The performance of the proposed PCF sensor is numerically investigated and designed by COMSOL software v.5.3a. Fabrication feasibility of developed geometry is also stated here.

Development of dispersive solid phase extraction utilizing folic acid as an efficient and green sorbent followed by dispersive liquid-liquid microextraction for the extraction of some plasticizers from aqueous samples.

In this investigation, folic acid has been used as an efficient and green sorbent in dispersive solid phase extraction for the extraction of di(2-ethylhexyl) adipate and three phthalate esters from the plastic-packed liquids before their determination with gas chromatography-flame ionization detection. This is the first report on the application of pure folic acid as a sorbent. In this work, limits of detection and quantification were in the ranges of 0.13-0.46 and 0.43-1.50µg/L, respectively. Relative standard deviations were in the ranges of 2-5% for intra- (n=6) and 4-7% for interday (n=4) precisions at a concentration of 20µg/L for each analyte. Enrichment factors and extraction recoveries were obtained in the ranges of 365-670 and 45-84%, respectively. Efficiency of the method was evaluated by analyzing the analytes in various plastic-packed liquids.

Detection of EGFR Mutations in cfDNA and CTCs, and Comparison to Tumor Tissue in Non-Small-Cell-Lung-Cancer (NSCLC) Patients.

Lung cancer is the leading cause of cancer-related mortality worldwide. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapies, based on the evaluation of EGFR mutations, have shown dramatic clinical benefits. EGFR mutation assays are mainly performed on tumor biopsies, which carry risks, are not always successful and give results relevant to the timepoint of the assay. To detect secondary EGFR mutations, which cause resistance to 1st and 2nd generation TKIs and lead to the administration of a 3rd generation drug, effective and non-invasive monitoring of EGFR mutation status is needed. Liquid biopsy analytes, such as circulating tumor cells (CTCs) and circulating tumor DNA (cfDNA), allow such monitoring over the course of the therapy. The aim of this study was to develop and optimize a workflow for the evaluation of cfDNA and CTCs in NSCLC patients all from one blood sample. Using Vortex technology and EntroGen ctEGFR assay, EGFR mutations were identified at 0.5 ng of DNA (∼83 cells), with a sensitivity ranging from 0.1 to 2.0% for a total DNA varying from 25 ng (∼4 CTCs among 4000 white blood cells, WBCs) to 1 ng (∼4 CTCs among 200 WBCs). The processing of plasma-depleted-blood provided comparable capture recovery as whole blood, confirming the possibility of a multimodality liquid biopsy analysis (cfDNA and CTC DNA) from a single tube of blood. Different anticoagulants were evaluated and compared in terms of respective performance. Blood samples from 24 NSCLC patients and 6 age-matched healthy donors were analyzed with this combined workflow to minimize blood volume needed and sample-to-sample bias, and the EGFR mutation profile detected from CTCs and cfDNA was compared to matched tumor tissues. Despite the limited size of the patient cohort, results from this non-invasive EGFR mutation analysis are encouraging and this combined workflow represents a valuable means for informing therapy selection and for monitoring treatment of patients with NSCLC.

A novel hollow core photonic sensor for liquid analyte detection in the terahertz spectrum: design and analysis

A novel hollow core photonic crystal fiber (PCF) is proposed for biochemical analyte detection in the terahertz regime. The prime objective of the work is to increase the sensitivity but other significant features like effective material loss, confinement loss, effective area, numerical aperture and dispersion have been thoroughly investigated over a wide bandwidth using COMSOL version 5.3. Numerical simulation shows that a maximum chemical sensitivity of 99.76% 99.44% and 99.39% can be obtained for benzene, water and methanol respectively at optimum operating conditions. The symmetry in design makes the proposed structure easily feasible to be fabricated using the existing fabrication technologies. Thus it is believed that the proposed PCF has the potential due to its higher sensitivity and lower effective material loss to uplift the standard of PCF sensors and open a new window in this field of research.

Nanometer-Scale Heterogeneous Interfacial Sapphire Wafer Bonding for Enabling Plasmonic-Enhanced Nanofluidic Mid-Infrared Spectroscopy.

As one of the most effective surface-enhanced infrared absorption (SEIRA) techniques, metal-insulator-metal structured metamaterial perfect absorbers possess an ultrahigh sensitivity and selectivity in molecular infrared fingerprint detection. However, most of the localized electromagnetic fields (i.e., hotspots) are confined in the dielectric layer, hindering the interaction between analytes and hotspots. By replacing the dielectric layer with the nanofluidic channel, we develop a sapphire (Al2O3)-based mid-infrared (MIR) hybrid nanofluidic-SEIRA (HN-SEIRA) platform for liquid sensors with the aid of a low-temperature interfacial heterogeneous sapphire wafer direct bonding technique. The robust atomic bonding interface is confirmed by transmission electron microscope observation. We also establish a design methodology for the HN-SEIRA sensor using coupled-mode theory to carry out the loss engineering and experimentally validate its feasibility through the accurate nanogap control. Thanks to the capillary force, liquid analytes can be driven into sensing hotspots without external actuation systems. Besides, we demonstrate an in situ real-time dynamic monitoring process for the acetone molecular diffusion in deionized water. A small concentration change of 0.29% is distinguished and an ultrahigh sensitivity (0.8364 pmol-1 %) is achieved. With the aid of IR fingerprint absorption, our HN-SEIRA platform brings the selectivity of liquid molecules with similar refractive indexes. It also resolves water absorption issues in traditional IR liquid sensors thanks to the sub-nm long light path. Considering the wide transparency window of Al2O3 in MIR (up to 5.2 μm), the HN-SEIRA platform covers more IR absorption range for liquid sensing compared to fused glass commonly used in micro/nanofluidics. Leveraging the aforementioned advantages, our work provides insights into developing a MIR real-time liquid sensing platform with intrinsic IR fingerprint selectivity, label-free ultrahigh sensitivity, and ultralow analyte volume, demonstrating a way toward quantitative molecule identification and dynamic analysis for the chemical and biological reaction processes.

Numerical investigation of a highly sensitive plasmonic refractive index sensor utilizing hexagonal lattice of photonic crystal fiber

In this paper, a gold-coated photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) technology is proposed through comprehensive numerical analysis for detection of numerous biological and biochemical analytes. The proposed sensor is designed with a simplified hexagonal geometrical structure for ease of fabrication process. Also, to facilitate the ease of sensing and real-time detection capability, the external sensing approach is employed. To investigate the performance of the proposed sensor, both the amplitude and wavelength interrogation methods are utilized. For analyte RI of 1.33 to 1.37, the sensor offers a wavelength sensitivity of 3000 nm/RIU to 13,000 nm/RIU with a maximum spectral resolution of 7.69×10-6 RIU. The proposed sensor also provides a maximum possible amplitude sensitivity of 953.23 RIU−1. In addition, the sensor provides an excellent figure of merit (FOM) with a maximum value of 228.01 RIU−1. Furthermore, the influence of the structural parameters on the sensor performance is analyzed by tuning the thickness of the gold layer, pitch, and diameter of air holes of the PCF. The proposed sensor reveals a promise to sense and detect different liquid analytes of refractive index (RI) ranging from 1.33 to 1.37 having enhanced performance characteristics.

Core-Shell Magnetic Nanoparticles for Highly Sensitive Magnetoelastic Immunosensor.

A magnetoelastic (ME) biosensor for wireless detection of analytes in liquid is described. The ME biosensor was tested against human IgG in the range 0–20 μg∙mL−1. The sensing elements, anti-human IgG produced in goat, were immobilized on the surface of the sensor by using a recently introduced photochemical immobilization technique (PIT), whereas a new amplification protocol exploiting gold coated magnetic nanoparticles (core-shell nanoparticles) is demonstrated to significantly enhance the sensitivity. The gold nanoflowers grown on the magnetic core allowed us to tether anti-human IgG to the nanoparticles to exploit the sandwich detection scheme. The experimental results show that the 6 mm × 1 mm × 30 μm ME biosensor with an amplification protocol that uses magnetic nanoparticles has a limit of detection (LOD) lower than 1 nM, works well in water, and has a rapid response time of few minutes. Therefore, the ME biosensor is very promising for real-time wireless detection of pathogens in liquids and for real life diagnostic purpose.

A high linearity refractive index sensor based on D-shaped photonic-crystal fiber with built-in metal wires

We proposed a D-shaped photonic crystal fiber refractive index sensor based on surface plasmon resonance for the detection of refractive-index (RI) liquid analytes between 1.27 and 1.37. In contrast to the common D-shaped structure photonic crystal fiber, three metal wires were added between the D-surface and top level air holes in our design, which prevent the analytes from contacting the metal. It is particularly suitable for detecting some analytes which are easy to react with metal. The sensing performance of D-shaped photonic crystal fiber was studied by the finite element method. Simulation result shows that the sensor has a very good linearity. The adjusted R2 values of resonance wavelengths fitting lines are 0.9996 in 1.27−1.32. The sensitivity of the designed sensor can be as high as 11,500 nm/RIU, and a high resolution of 8.7 × 10−6 RIU is achieved when na = 1.36.An average sensitivity of 8,846.67 nm/RIU in the sensing range 1.27−1.32, and 10,812 nm/RIU in 1.33−1.37 with high linearity is obtained. The D-shaped optical fiber usually realizes the sensing function by coating a metal film, but the method of adding metal wires has rarely been reported before. Owing to the high linearity, high resonance intensity and sensitivity, the proposed sensor can find important applications in environmental, biological and biochemical analytes detection.