This article provides a comprehensive review of biosensing with DNAzymes, providing an overview of different sensing applications while highlighting major progress and seminal contributions to the field of portable biosensor devices and point-of-care diagnostics. Specifically, the field of functional nucleic acids is introduced, with a specific focus on DNAzymes. The incorporation of DNAzymes into bioassays is then described, followed by a detailed overview of recent advances in the development of in vivo sensing platforms and portable sensors incorporating DNAzymes for molecular recognition. Finally, a critical perspective on the field, and a summary of where DNAzyme-based devices may make the biggest impact are provided.

Biosensing with DNAzymes

Temperature is one of the most fundamental physical properties to characterize various physical, chemical, and biological processes. Even a slight change in temperature could have an impact on the status or dynamics of a system. Thus, there is a great need for high-precision and large-dynamic-range temperature measurements. Conventional temperature sensors encounter difficulties in high-precision thermal sensing on the submicron scale. Recently, optical whispering-gallery mode (WGM) sensors have shown promise for many sensing applications, such as thermal sensing, magnetic detection, and biosensing. However, despite their superior sensitivity, the conventional sensing method for WGM resonators relies on tracking the changes in a single mode, which limits the dynamic range constrained by the laser source that has to be fine-tuned in a timely manner to follow the selected mode during the measurement. Moreover, we cannot derive the actual temperature from the spectrum directly but rather derive a relative temperature change. Here, we demonstrate an optical WGM barcode technique involving simultaneous monitoring of the patterns of multiple modes that can provide a direct temperature readout from the spectrum. The measurement relies on the patterns of multiple modes in the WGM spectrum instead of the changes of a particular mode. It can provide us with more information than the single-mode spectrum, such as the precise measurement of actual temperatures. Leveraging the high sensitivity of WGMs and eliminating the need to monitor particular modes, this work lays the foundation for developing a high-performance temperature sensor with not only superior sensitivity but also a broad dynamic range. Extremely precise measurement of temperature using devices known as whispering-gallery mode (WGM) sensors can be greatly improved using a technique that simultaneously monitors different modes, or patterns, of the optical signals. WGM sensors rely on the sustained circulation of light within closed concave microstructures—discs, rings, or spheres—similar to the movement of sound waves in whispering galleries such as the dome of St. Paul’s Cathedral in London. Jie Liao and Lan Yang at Washington University in St. Louis, Missouri, USA, developed procedures to analyse the effect of temperature on the collective patterns of light signals in WGM sensors. The results are converted into optical barcodes which indicate the temperature directly. This multimode system overcomes significant limitations imposed by the restricted range and less direct monitoring methods of existing single-mode sensors.

/pdf/optical-whispering-gallery-mode-barcodes-for-high-precision-2wl94mydtq.pdf

Optical whispering-gallery mode barcodes for high-precision and wide-range temperature measurements.

Optical whispering-gallery-mode microresonators with ultrahigh quality factors and small mode volumes have played an important role in modern physics. They have been demonstrated as a diverse platform for a wide range of applications in photonics, such as nonlinear optics, optomechanics, quantum optics, and information processing. Thermal behaviors induced by power build-up in the resonators or environmental perturbations are ubiquitous in high-quality-factor whispering-gallery-mode resonators and have played an important role in their operation for various applications. In this review, we discuss the mechanisms of laser-field-induced thermal nonlinear effects, including thermal bistability and thermal oscillation. With the help of the thermal bistability effect, optothermal spectroscopy and optical nonreciprocity have been demonstrated. By tuning the temperature of the environment, the resonant mode frequency will shift, which can also be used for thermal sensing/tuning applications. The thermal locking technique and thermal imaging mechanisms are discussed briefly. Finally, we review some techniques employed to achieve thermal stability in a high-quality-factor resonator system.

/pdf/optothermal-dynamics-in-whispering-gallery-microresonators-12uurlyr2n.pdf

Optothermal dynamics in whispering-gallery microresonators

Overview of the coupling methods used in whispering gallery mode resonator systems for sensing

Solute concentration sensing in two aqueous solution using an optical metamaterial sensor

Optical whispering-gallery-mode (WGM) microresonator-based sensors with high sensitivity and low detection limit down to single unlabeled biomolecules show high potential for disease diagnosis and clinical application. However, most WGM microresonator-based sensors, which are packed in a microfluidic cell, are a “closed” sensing configuration that prevents changing and sensing the surrounding liquid refractive index (RI) of the microresonator immediately. Here, we present an “open” sensing configuration in which the WGM microdisk laser is directly covered by a water droplet and pumped by a water-immersion-objective (WIO). This allows monitoring the chemical reaction progress in the water droplet by tracking the laser wavelength. A proof-of-concept demonstration of chemical sensor is performed by observing the process of salt dissolution in water and diffusion of two droplets with different RI. This WIO pumped sensing configuration provides a path towards an on-chip chemical sensor for studying chemical reaction kinetics in real time.

https://www.mdpi.com/2079-4991/9/3/479/pdf

On-Chip Real-Time Chemical Sensors Based on Water-Immersion-Objective Pumped Whispering-Gallery-Mode Microdisk Laser

Combining whispering gallery mode optofluidic microbubble resonator sensor with GR-5 DNAzyme for ultra-sensitive lead ion detection

Liquid droplet and quasi-droplet whispering gallery mode (WGM) microcavities have been widely studied recently for the enhanced spatial overlap between the liquid and WGM field, especially in sensing applications. However, the fragile cavity structure and the evaporation of liquid limit its practical applications. Here, stable, packaged, quasi-droplet and droplet microcavities are proposed and fabricated for thermal sensing with high sensitivity. The sensitivity and electromagnetic field intensity distribution are analyzed by Mie theory, and a quantified definition of the quasi-droplet is presented for the first time to the best of our knowledge. By doping dye material directly into the liquid, lasing packaged droplet and quasi-droplet microcavity sensors with a high thermal sensitivity of up to 205.3 pm/°C are experimentally demonstrated. The high sensitivity, facile fabrication, and mechanically robust properties of the optofluidic, packaged droplet microresonator make it a promising candidate for future integrated photonic devices.

Packaged Droplet Microresonator for Thermal Sensing with High Sensitivity.

An optofluidic microbubble Fabry–Perot (OMBFP) cavity was investigated. In contrast to plane-plane FP (PPFP) cavities, the optical mode confinement and stability in an OMBFP were significantly enhanced. The optical properties of the OMBFP cavity, including the quality (Q) factor, effective mode area, mode distribution as a function of the core refractive index, microbubble position, and mirror tilt angle, were investigated systematically using the finite element method. In optofluidic lasing experiments, a low lasing threshold of 1.25 µJ/mm2, which was one order magnitude lower than that of the PPFP, was achieved owing to improved modal lateral confinement. Since the microbubble acts as a micro-lens and microfluidic channel in the parallel FP cavity, mode selection and cell-dye laser were easily realized in the OMBFP cavity.

Optofluidic microbubble Fabry–Pérot cavity

This study introduces design and coupling techniques, which bridge an opaque liquid metal, optical WGM mode, and mechanical mode into an opto-mechano-fluidic microbubble resonator (MBR) consisting of a dielectric silica shell and liquid metal core. Benefiting from the conductivity of the liquid metal, Ohmic heating was carried out for the MBR by applying current to the liquid metal to change the temperature of the MBR by more than 300 °C. The optical mode was thermally tuned (>3 nm) over a full free spectral range because the Ohmic heating changed the refractive index of the silica and dimeter of the MBR. The mechanical mode was thermally tuned with a relative tuning range of 9% because the Ohmic heating changed the velocity and density of the liquid metal.

Liang Fu

Papers

On-Chip Real-Time Chemical Sensors Based on Water-Immersion-Objective Pumped Whispering-Gallery-Mode Microdisk Laser

Combining whispering gallery mode optofluidic microbubble resonator sensor with GR-5 DNAzyme for ultra-sensitive lead ion detection

Packaged Droplet Microresonator for Thermal Sensing with High Sensitivity.

Optofluidic microbubble Fabry–Pérot cavity

Tunable optofluidic liquid metal core microbubble resonator