Single-Molecule Optical Biosensing: Recent Advances and Future Challenges

Dey, Swayandipta; Dolci, Mathias; Zijlstra, Peter

doi:10.1021/acsphyschemau.2c00061

Cited by 23 publications

(17 citation statements)

References 95 publications

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“…The latter are the most common and consist of a circular structure (e.g., a micro-sphere, micro-disk, or micro-toroid), where the light is confined. Resonator biosensors can be found in arrangements such as silicon-on-isolator (SOI) [ 78 ], opto-fluidic ring resonator (OFRR) [ 79 ], subwavelength grating (SWG) [ 80 ] and whispering gallery mode (WGM) [ 81 ].…”

Section: Main Optical Biosensor Componentsmentioning

confidence: 99%

“…WGM are found in the cavity as a result of total reflection at the exterior cavity contact. It has a low internal loss and, hence, a weakly constrained near-field, yet a greatly elevated Q factor [ 81 ].…”

Section: Main Optical Biosensor Componentsmentioning

confidence: 99%

“…On the other hand, the detection of single molecules is a powerful technology that avoids bulk averaging and provides direct information on individual molecules [ 144 ]. Although single-molecule biosensors do not yet outperform ensemble-averaged approaches in terms of sensitivity, they show considerable improvement in affinity [ 81 ]. Single-molecule biosensors have been extensively studied in the healthcare field [ 145 ], making them a source of future research if these developments are extrapolated to environmental detection.…”

Section: Key Trends and Future Perspectivementioning

confidence: 99%

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Optical Biosensors and Their Applications for the Detection of Water Pollutants

et al. 2023

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The correct detection and quantification of pollutants in water is key to regulating their presence in the environment. Biosensors offer several advantages, such as minimal sample preparation, short measurement times, high specificity and sensibility and low detection limits. The purpose of this review is to explore the different types of optical biosensors, focusing on their biological elements and their principle of operation, as well as recent applications in the detection of pollutants in water. According to our literature review, 33% of the publications used fluorescence-based biosensors, followed by surface plasmon resonance (SPR) with 28%. So far, SPR biosensors have achieved the best results in terms of detection limits. Although less common (22%), interferometers and resonators (4%) are also highly promising due to the low detection limits that can be reached using these techniques. In terms of biological recognition elements, 43% of the published works focused on antibodies due to their high affinity and stability, although they could be replaced with molecularly imprinted polymers. This review offers a unique compilation of the most recent work in the specific area of optical biosensing for water monitoring, focusing on both the biological element and the transducer used, as well as the type of target contaminant. Recent technological advances are discussed.

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Section: Main Optical Biosensor Componentsmentioning

confidence: 99%

Section: Main Optical Biosensor Componentsmentioning

confidence: 99%

Section: Key Trends and Future Perspectivementioning

confidence: 99%

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Optical Biosensors and Their Applications for the Detection of Water Pollutants

et al. 2023

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“…A strategy to increase sensitivity is by harnessing single-molecule measurement principles. − Examples are the single-molecule enzyme-linked immunosorbent assay (digital ELISA), , single-molecule fluorescence, , single-molecule plasmonics, , and single-molecule nanopores. , However, it is difficult to enable continuous real-time biosensing because (1) the underlying sensing principle needs to be reversible, such that increases as well as decreases of analyte concentration can be continuously followed as a function of time; (2) time-dependent signals need to be available in high throughput, such that sufficient single-molecule statistics can be collected in a limited amount of time; and (3) a signal processing methodology should be developed that can continuously analyze the data in real time and that is able to control the trade-off between analysis time and the required analytical precision.…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Single-Molecule Sensors: How Can the Signals Be Analyzed in Real Time for Achieving Real-Time Continuous Biosensing?

Bergkamp

Cajigas²,

IJzendoorn

et al. 2023

ACS Sens.

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Single-molecule sensors collect statistics of single-molecule interactions, and the resulting data can be used to determine concentrations of analyte molecules. The assays are generally end-point assays and are not designed for continuous biosensing. For continuous biosensing, a single-molecule sensor needs to be reversible, and the signals should be analyzed in real time in order to continuously report output signals, with a well-controlled time delay and measurement precision. Here, we describe a signal processing architecture for real-time continuous biosensing based on high-throughput single-molecule sensors. The key aspect of the architecture is the parallel computation of multiple measurement blocks that enables continuous measurements over an endless time span. Continuous biosensing is demonstrated for a single-molecule sensor with 10,000 individual particles that are tracked as a function of time. The continuous analysis includes particle identification, particle tracking, drift correction, and detection of the discrete timepoints where individual particles switch between bound and unbound states, yielding state transition statistics that relate to the analyte concentration in solution. The continuous real-time sensing and computation were studied for a reversible cortisol competitive immunosensor, showing how the precision and time delay of cortisol monitoring are controlled by the number of analyzed particles and the size of the measurement blocks. Finally, we discuss how the presented signal processing architecture can be applied to various single-molecule measurement methods, allowing these to be developed into continuous biosensors.

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“…Single-molecule fluorescence techniques are essential to investigate and understand the molecular mechanisms behind biological processes. [1][2][3][4][5] A broad class of single-molecule spectroscopy methods has been developed, including fluorescence time trace analysis, [6] fluorescence correlation spectroscopy (FCS), [7] Förster resonance energy transfer (FRET), [8,9] single particle DOI: 10.1002/adom.202300168 tracking (SPT), [10] or multiparameter fluorescence detection (MFD). [11,12] With these techniques, watching single molecule dynamics on timescales from milliseconds to minutes is particularly common.…”

Section: Introductionmentioning

confidence: 99%

Achieving High Temporal Resolution in Single‐Molecule Fluorescence Techniques Using Plasmonic Nanoantennas

Tiwari

Roy

Claude

et al. 2023

Advanced Optical Materials

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Single‐molecule fluorescence techniques are essential for investigating the molecular mechanisms in biological processes. However, achieving sub‐millisecond temporal resolution to monitor fast molecular dynamics remains a significant challenge. The fluorescence brightness is the key parameter that generally defines the temporal resolution for these techniques. Conventional microscopes and standard fluorescent emitters fall short in achieving the high brightness required for sub‐millisecond monitoring. Plasmonic nanoantennas are proposed as a solution, but despite huge fluorescence enhancement having been obtained with these structures, the brightness generally remains below 1 million photons/s/molecule. Therefore, the improvement of temporal resolution is overlooked. This article presents a method for achieving high temporal resolution in single‐molecule fluorescence techniques using plasmonic nanoantennas, specifically optical horn antennas. This work demonstrates about 90% collection efficiency of the total emitted light, reaching a high fluorescence brightness of 2 million photons/s/molecule in the saturation regime. This enables observations of single molecules with microsecond binning time and fast fluorescence correlation spectroscopy measurements. This work expands the applications of plasmonic antennas and zero‐mode waveguides in the fluorescence saturation regime toward brighter single‐molecule signal, faster temporal resolutions, and improved detection rates to advance fluorescence sensing, DNA sequencing, and dynamic studies of molecular interactions.

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Single-Molecule Optical Biosensing: Recent Advances and Future Challenges

Cited by 23 publications

References 95 publications

Optical Biosensors and Their Applications for the Detection of Water Pollutants

Optical Biosensors and Their Applications for the Detection of Water Pollutants

High-Throughput Single-Molecule Sensors: How Can the Signals Be Analyzed in Real Time for Achieving Real-Time Continuous Biosensing?

Achieving High Temporal Resolution in Single‐Molecule Fluorescence Techniques Using Plasmonic Nanoantennas

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