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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.

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 level or single-molecule analysis. To break this limitation, we developed an all-optical active method termed optothermophoretic flipping (OTF). The biomolecules were first enriched to aggregation and then 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. We achieved 36.9-fold sensitivity enhancement in this first temporal modulated approach that manipulates biomolecules for interaction enhancement. This method promises to be widely adopted in various biosensing platforms that require ultrasensitivity in colloidal sciences and biochemical studies.

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.

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 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.