Wavelength Division Multiplexing-Based High-Sensitivity Surface Plasmon Resonance Imaging Biosensor for High-Throughput Real-Time Molecular Interaction Analysis.

In this study, we report the successful development of a novel high-sensitivity intensity-based Surface Plasmon Resonance imaging (SPRi) biosensor and its application for detecting molecular interactions. By optimizing the excitation wavelength and employing a wavelength division multiplexing (WDM) algorithm, the system can determine the optimal excitation wavelength based on the initial refractive index of the sample without adjusting the incidence angle. The experimental results demonstrate that the refractive index resolution of the system reaches 1.77×10-6 RIU. Moreover, it can obtain the optimal excitation wavelength for samples with an initial refractive index in the range of 1.333 to 1.370 RIU and accurately monitor variations within the range of 0.0037 RIU without adjusting the incidence angle. Additionally, our new SPRi technique realized real-time detection of high-throughput biomolecular binding processes, enabling analysis of kinetic parameters. This research is expected to advance the development of more accurate SPRi technologies for molecular interaction analysis.

Coffee Ring Effect Enhanced Surface Plasmon Resonance Imaging Biosensor via 2-λ Fitting Detection Method.

SPR biosensors have been extensively used for investigating protein-protein interactions. However, in conventional surface plasmon resonance (SPR) biosensors, detection is limited by the Brownian-motion-governed diffusion process of sample molecules in the sensor chip, which makes it challenging to detect biomolecule interactions at ultra-low concentrations. Here, we propose a highly sensitive SPR imaging biosensor which exploits the coffee ring effect (CRE) for in situ enrichment of molecules on the sensing surface. In addition, we designed a wavelength modulation system utilizing two LEDs to reduce the system cost and enhance the detection speed. Furthermore, a detection limit of 213 fM is achieved, which amounts to an approximately 365 times improvement compared to traditional SPR biosensors. With further development, we believe that this SPR imaging system with high sensitivity, less sample consumption, and faster detection speed can be readily applied to ultra-low-concentration molecular detection and interaction analysis.

Thermal stability and decomposition kinetics of mixed-cation halide perovskites.

Organic-inorganic halide perovskites (OIHPs) have emerged as one of the most efficient photovoltaic materials due to their superior properties. However, improving their stability remains a key challenge. Herein, we investigate the thermal decomposition properties of OIHP FAxMA1-xPbI3 with mixed cations of formamidinium (FA) and methylammonium (MA). Using thermogravimetric analysis together with Fourier transform infrared spectroscopy, we identify and monitor the gaseous decomposition products as a function of temperature and cation composition. Thermal decomposition products of both MA and FA cations were observed at all stages of the thermal decomposition process, contrary to previous expectations. The yield, release sequence and kinetics of the organic gaseous products were found to depend strongly on the ratio between FA and MA cations. Furthermore, cesium ion doping was investigated as a potential strategy to improve the thermal stability of mixed cation perovskites. These results provide new insights into the effect of cation mixing on perovskite stability, suggesting that optimizing the cation ratios and decomposition pathways can guide approaches to boost the stability and performance of mixed cation perovskites.

Intensity Interrogation-Based High-Sensitivity Surface Plasmon Resonance Imaging Biosensor for Apoptosis Detection in Cancer.

Intensity interrogation-based surface plasmon resonance imaging (ISPRi) sensing has a simple schematic design and is the most widely used surface plasmon resonance technology at present. In this study, we report the successful development of a novel high-sensitivity ISPRi biosensor and its application for apoptosis detection in cancer cells. By optimizing the excitation wavelength and excitation angle, we achieved a refractive index resolution (RIR) of 5.20 × 10-6 RIU. Importantly, the biosensor has been tested and validated for high-throughput and label-free detection of activated caspase-3 with its specific inhibitor Z-DEVD-FMK in apoptotic cells. Therefore, this study describes a novel molecular imaging system to monitor apoptosis in cancers for disease diagnosis and/or evaluation of therapeutic efficacy of anti-cancer drugs.

Quasi-phase extraction-based surface plasmon resonance imaging method for coffee ring effect monitoring and biosensing.

Wavelength interrogation surface plasmon resonance imaging (WSPRi) sensing has unique advantages in high-throughput imaging detection. The refractive index resolution (RIR) of WSPRi is limited to the order of 10-6 RIU. This paper demonstrates a novel WSPRi sensing system with a wavelength scanning device of an acousto-optic tunable filter (AOTF) and a low-cost speckle-free SPR excitation source of a halogen lamp. We developed a sensitive quasi-phase extraction method for data processing. The new technique achieved an RIR of 8.84×10-7 RIU, which is the first WSPRi system that has an RIR in the order of 10-7 RIU. Moreover, we performed a real-time recording of the formation of the coffee ring effect during brine evaporation and enhanced the biosensor performance of SPR for the first time. We believe the higher RIR and accuracy of the system will benefit more potential applications toward exploring the biomolecules' behaviors in biological and biochemistry studies.

A capacitance sensing method with trans-impedance based readout circuit and adaptive filtering for micro-gyro.

Trans-impedance amplifier (TIA) based capacitance-voltage (C-V) readout circuit is an attractive choice for micro-machined gyroscope for its simplicity and superior performance. In this work, the noise and the C-V gain characteristics of the TIA circuit are analyzed in detail. Then, a TIA based readout circuit with a C-V gain of about 286 dB is designed, and a series of experiments are conducted to test the performance of the circuit. Both the analysis and test results show that T-network TIA should be avoided as far as possible for its poor noise performance. All results also show that there is a signal-to-noise ratio (SNR) limit for the TIA based readout circuit, and the SNR can only be further improved by filtering. Hence, an adaptive finite impulse response filter is designed to further improve the SNR of the sensed signal. For a gyroscope with a peak-to-peak variable capacitance of about 200 aF, a SNR of 22.8 dB can be achieved by the designed circuit and a SNR of 47 dB can be obtained by further adaptive filtering. Finally, the solution presented in this paper achieves a capacitive sensing resolution of 0.9 aF.

Wavelength sequential selection technique for high-throughput multi-channel phase interrogation surface plasmon resonance imaging sensing.

Phase interrogation surface plasmon resonance (P-SPR) biosensors have the highest sensitivity among different types of surface plasmon resonance (SPR) biosensors. However, P-SPR sensors have small dynamic detection range and complex device configuration. To solve these two problems, we designed a multi-channel P-SPR imaging (mcP-SPRi) sensing platform based on a common-path ellipsometry scheme. A wavelength sequential selection (WSS) technique for P-SPRi sensing is developed to select the optimal sensing wavelengths according to different refractive indexes (RIs) of the samples, so the inconsistency of SPR signal response for different biomolecule types caused by the small dynamic detection range is eliminated. And a dynamic detection range of 3.7×10-3 RIU is achieved, which is the largest among the current mcP-SPRi biosensors. Remarkably, the individual SPR phase image acquisition time has been greatly reduced to 1s by using WSS method instead of whole spectrum scanning, which enables the high-throughput mcP-SPRi sensing.

Surface Plasmon Resonance Microscopy Based on Total Internal Reflection.

Surface plasmon resonance microscopy (SPRM) has been widely employed in biological fields because of its high spatial resolution and label-free detection modality. In this study, SPRM based on total internal reflection (TIR) is studied via a home-built SPRM system, and the principle of imaging of a single nanoparticle is analyzed as well. By designing a ring filter and combining it with the deconvolution algorithm in Fourier space, the parabolic tail of the nanoparticle image is removed, in which a spatial resolution of 248 nm is obtained. In addition, we also measured the specific binding between the human IgG antigen and goat anti-human IgG antibody using the TIR-based SPRM. The experimental results have proved that the system can image sparse nanoparticles and monitor biomolecular interactions.

Design and Simulation of a Ratiometric SPR Sensor Based on a 2D van der Waals Heterojunction for Refractive Index Measurement.

Surface plasmon resonance (SPR) sensors have been widely applied in many fields because of their advantages of working in real time and high sensitivity. However, because the spectrum of an SPR sensor is easily affected by the smoothness of the metal surface, this type of sensor has obvious disadvantages in the application of quantitative detection. We designed an SPR refractive index sensor for molecular detection that has the advantage of quantifiability. A ratio spectral quantitative analysis method was established based on the two coherent dips of the SPR spectrum formed by the strong coupling effect between the surface plasmon polaritons and the excitons of the J-aggregate molecule 5,6-dichloro-2-[3-[5,6-dichloro-1-ethyl-3-(4-sulfobutyl)-2-benzimidazoline subunit] propenyl]-3-ethyl-1-(4-sulfobutyl) benzimidazole hydroxide inner salt (TDBC). The introduced MoS2/graphene van der Waals heterojunction produced an effective charge transfer to the Ag film, resulting in significant electric field enhancement at the sensing interface and further improving the detection sensitivity of the sensor. The simulation results showed that for 43 nm Ag film, for example, the ratiometric SPR sensor with the Ag film structure can obtain 16.12 RIU-1 sensing sensitivity, applied to the detection of gas molecules, while the SPR sensor with single-layer graphene and three layers of MoS2 heterostructures can obtain 50.68 RIU-1 sensing sensitivity. The addition of van der Waals heterostructures can significantly improve sensing performance by 215%.

Corrigendum: High-Sensitive Surface Plasmon Resonance Imaging Biosensor Based on Dual-Wavelength Differential Method.

[This corrects the article DOI: 10.3389/fchem.2021.801355.].

Optothermophoretic flipping method for biomolecule interaction enhancement.

The widely used surface-based biomolecule sensing scheme has greatly facilitated the investigation of protein-protein interactions in lab-on-a-chip microfluidic systems. However, in most biosensing schemes, the interactions are driven in a passive way: The overall sensing time and sensitivity are totally dependent on the Brownian diffusion process, which has greatly hindered their efficiency, especially at low concentration levels or single-molecule analysis. To break this limitation, we developed an all-optical active method termed optothermophoretic flipping (OTF). It is the first temporal modulated method that biomolecules were enriched and pushed to their counterparts for effective contact via a flipped thermophoresis. As a proof-of-concept experiment, we tested its performance via antibody-antigen binding on a surface plasmon resonance imaging (SPRi) platform. Compared with the interaction solely based on Brownian diffusion, we achieved a 23.6-fold sensitivity increment in biomolecule interactions sensing. This method has opened new opportunities for various biosensing platforms that require high-sensitivity in colloidal sciences and biochemical studies.

High-Sensitive Surface Plasmon Resonance Imaging Biosensor Based on Dual-Wavelength Differential Method.

Intensity interrogation surface plasmon resonance (ISPR) sensing has a simple schematic design and is the most widely used surface plasmon resonance technology at present. However, it has relatively low sensitivity, especially for ISPR imaging (ISPRi). In this paper, a new technique for the real-time monitoring of biomolecule binding on sensor surfaces via ISPRi detection is described. The technique is based on the interrogation of the differential value of two intensities at two specific wavelengths from the reflected light spectrum. In addition, we also optimized the selection of dual-wavelength parameters under different circumstances to achieve the highest sensitivity. The new technique achieved a refractive index resolution (RIR) of 2.24 × 10-6 RIU, which is far beyond that of traditional ISPRi technique. Moreover, our new ISPRi technique also realized the real-time detection of high-throughput biomolecular binding. This study is expected to promote the development of faster and more accurate SPRi technologies.

Phase interrogation surface plasmon resonance hyperspectral imaging sensor for multi-channel high-throughput detection.

Phase interrogation surface plasmon resonance (SPR) imaging is, in principle, suitable in multiple samples and high-throughput detection, but the refractive index difference of various samples can be largely varied, while the dynamic range of phase interrogation SPR is narrow. So it is difficult to perform multi-sample detection in phase interrogation mode. In this paper, we successfully designed a multi-channel phase interrogation detection SPR imaging sensing scheme based on a common optical interference path between p- and s-polarized light without using any mechanical moving components. The fixed optical path difference between p- and s-polarized light is introduced by a birefringence crystal to produce sinusoidal spectral interference fringes. We adopted a time-division-multiplexing peak-finding algorithm to track the resonance wavelength so that the detection range can cover every channel. The phase values which carry the high sensitivity signal of the corresponding samples are calculated by the iterative parameter scanning cross-correlation algorithm.

Ultrafast Surface Plasmon Resonance Imaging Sensor via the High-Precision Four-Parameter-Based Spectral Curve Readjusting Method.

A variety of surface plasmon resonance (SPR) sensing devices have been extensively used in biochemical detection for their characteristics of label-free, highly sensitive, and faster detecting. Among them, the spectrum-based SPR sensing devices have offered us great advantages in high-throughput sensing due to their large dynamic range and the possibility of detection resolution similar to that offered by angle interrogation. This paper demonstrates a spectrum-based SPR imaging sensing system with fast wavelength scanning capability achieved by an acousto-optic tunable filter (AOTF) and a low-cost and speckle-free halogen lamp implemented as the SPR excitation source. Especially, we developed a novel four-parameter-based spectral curve readjusting (4-PSCR) method for data processing, which offered us a faster and more accurate spectral data curve fitting process than the traditional polynomial fitting method. With the configuration, we have also conducted an SPR high-throughput detection of the novel coronavirus (COVID-19) spike protein, proving its application possibility in the screening of COVID-19 with high accuracy. We believe that the higher sensitivity and accuracy of the system have made it readily used in biochemical imaging and detecting applications.

High-throughput imaging surface plasmon resonance biosensing based on ultrafast two-point spectral-dip tracking scheme.

Wavelength interrogation surface plasmon resonance imaging (λSPRi) has potential in detecting 2-dimensional (2D) sensor array sites, but the resonance wavelength imaging rate limits the application of detecting biomolecular binding process in real time. In this paper, we have successfully demonstrated an ultrafast λSPRi biosensor system. The key feature is a two-point tracking algorithm that drives the liquid crystal tunable filter (LCTF) to achieve fast-tracking of the resonance wavelength movement caused by the binding of target molecules with the probe molecules on the sensing surface. The resonance wavelength measurement time is within 0.25s. To date, this is the fastest speed ever reported in λSPRi. Experiment results show that the sensitivity and dynamic are 2.4 × 10-6 RIU and 4.6 × 10-2 RIU, respectively. In addition, we have also demonstrated that the system has the capability of performing fast high-throughput detection of biomolecular interactions, which confirms that this fast real-time detecting approach is most suitable for high-throughput and label-free biosensing applications.

Phase interrogation SPR sensing based on white light polarized interference for wide dynamic detection range.

A phase surface plasmon resonance (SPR) sensing technology based on white light polarized interference in common-path geometry is reported. A halogen lamp is used as the excitation source of the SPR sensor. The fixed optical path difference (OPD) between p- and s-polarized light is introduced by a birefringence crystal to produce sinusoidal spectral interference fringes. The SPR phase is accurately extracted from the interference fringes using a novel iterative parameter-scanning cross-correlation algorithm. The dynamic detection range is expanded by tracking the best SPR wavelength, which is identified using a window Fourier algorithm. The experimental results show that the sensitivity of this SPR system was 1.3 × 10-7 RIU, and the dynamic detection range was 0.029 RIU. This sensor, not only simple to implement and cost efficient, requires no modulators.

Wavelength-scanning surface plasmon resonance microscopy: A novel tool for real time sensing of cell-substrate interactions.

This paper, for the first time, presents a wavelength-scanning surface plasmon resonance microscope (WS-SPRM) as a label-free biosensor capable of measuring cell-substrate interaction. The approach utilized a liquid crystal tunable filter (LCTF) as a fast and flexible wavelength-scanning device that can implement a wavelength-scanning and SPR imaging cycle within 1 s. The system was verified by monitoring the dynamics of cellular processes including cell detachment and electroporation of individual cells. It was found that the WS-SPRM presented better performance than the intensity-based SPRM (I-SPRM) in the imaging of cell adhesion. The results also indicated that the WS-SPRM exhibited a larger dynamic range in monitoring cell electroporation than that of I-SPRM. In summary, the developed WS-SPRM in this study provides a promising technique for real-time monitoring of cell-substrate interaction.

Wavelength-Scanning SPR Imaging Sensors Based on an Acousto-Optic Tunable Filter and a White Light Laser.

A fast surface plasmon resonance (SPR) imaging biosensor system based on wavelength interrogation using an acousto-optic tunable filter (AOTF) and a white light laser is presented. The system combines the merits of a wide-dynamic detection range and high sensitivity offered by the spectral approach with multiplexed high-throughput data collection and a two-dimensional (2D) biosensor array. The key feature is the use of AOTF to realize wavelength scan from a white laser source and thus to achieve fast tracking of the SPR dip movement caused by target molecules binding to the sensor surface. Experimental results show that the system is capable of completing a SPR dip measurement within 0.35 s. To the best of our knowledge, this is the fastest time ever reported in the literature for imaging spectral interrogation. Based on a spectral window with a width of approximately 100 nm, a dynamic detection range and resolution of 4.63 × 10-2 refractive index unit (RIU) and 1.27 × 10-6 RIU achieved in a 2D-array sensor is reported here. The spectral SPR imaging sensor scheme has the capability of performing fast high-throughput detection of biomolecular interactions from 2D sensor arrays. The design has no mechanical moving parts, thus making the scheme completely solid-state.

High-throughput imaging surface plasmon resonance biosensing based on an adaptive spectral-dip tracking scheme.

Imaging-based spectral surface plasmon resonance (λSPR) biosensing is predominantly limited by data throughput because of the multiplied data capacity emerging from 2-dimensional sensor array sites and the many data points required to produce an accurate measurement of the absorption dip. Here we present an adaptive feedback approach to address the data throughput issue in λSPR biosensing. A feedback loop constantly tracks the dip location while target-molecule binding occurs at the sensor surface. An adaptive window is then imposed to reduce the number of data points that each pixel has to capture without compromising measurement accuracy. Rapid wavelength scanning is performed with a liquid crystal tunable filter (LCTF). With the use of a feedback loop, our demonstration system can produce a dip measurement within 700ms, thus confirming that the reported λSPR approach is most suitable for real-time micro-array label-free biosensing applications.

Fast spectral surface plasmon resonance imaging sensor for real-time high-throughput detection of biomolecular interactions.

A fast surface plasmon resonance (SPR) imaging biosensor system based on wavelength interrogation using a liquid crystal tunable filter (LCTF) is presented. The system combines the merits of wide-dynamic detection range offered by the spectral approach and multiplexed high-throughput data collection with a two-dimensional (2-D) biosensor array. The key feature of the reported scheme is a feedback loop that drives the LCTF to achieve fast tracking of the SPR dip movement caused by the binding of target molecules to the sensor surface. Experimental results show that the system is capable of completing an SPR dip measurement within 4 s. Based on using a spectral window of about 100 nm, the experimental dynamic detection range and refractive index resolution are 4.63×10?2??RIU and 5.87×10?6??RIU, respectively. As also demonstrated herein using 2-D microsensor arrays, among the spectral SPR sensors, the reported system is most suitable for multiplexed label-free biosensing applications.