Abstract Label-free imaging of living cells below the optical diffraction limit poses great challenges for microscopy. Biologically relevant structural information remains Rayleigh and beyond reach conventional microscopes. Super-resolution techniques are typically based on non-linear stochastic response fluorescent labels which can be toxic interfere with cell function. In this paper we present, first time, live using sub-optical wavelength phonons. The axial resolution our system is...

Abstract This report presents an optical fibre-based endo-microscopic imaging tool that simultaneously measures the topographic profile and 3D viscoelastic properties of biological specimens through phenomenon time-resolved Brillouin scattering. uses intrinsic viscoelasticity specimen as a contrast mechanism without fluorescent tags or photoacoustic mechanisms. We demonstrate 2 μm lateral resolution 320 nm axial for cells Caenorhabditis elegans larvae. has enabled first ever stiffness...

At low frequencies ultrasound is a valuable tool to mechanically characterize and image biological tissues. There much interest in using high-frequency investigate single cells. Mechanical characterization of vegetal cells by measurement Brillouin oscillations has been demonstrated the GHz range. This paper presents method extend this technique from previously reported single-point measurements line scans into high-resolution acoustic imaging tool. Our uses three-layered...

Characterization of the elasticity biological cells is growing as a new way to gain insight into cell biology. Cell mechanics are related most aspects cellular behavior, and applications in research medicine broad. Current methods often limited since they require physical contact or lack resolution. From available for characterization elasticity, those relying on high frequency ultrasound (phonons) promising because offer label-free, (even super-optical) resolution compatibility with...

Abstract We show for the first time that a single ultrasonic imaging fibre is capable of simultaneously accessing 3D spatial information and mechanical properties from microscopic objects. The novel measurement system consists two ultrafast lasers excite detect high-frequency ultrasound nano-transducer was fabricated onto tip single-mode optical fibre. A signal processing technique also developed to extract nanometric in-depth measurements GHz frequency acoustic waves, while still allowing...

Advances in artificial intelligence (AI) show significant promise multiscale modeling and biomedical informatics, particularly the analysis of phonon microscopy (high-frequency ultrasound) data for cancer detection. This study addresses critical issues engineering time-resolved samples by tackling 'batch effect,' which arises from unavoidable technical variations between experiments, creating confounding variables that AI models may inadvertently learn. We present a multi-task conditional...

In order to work at higher ultrasonic frequencies, for instance, increase the resolution, it is necessary fabricate smaller and frequency transducers. This paper presents an transducer capable of being made a very small size operated GHz frequencies. The transducers are activated read optically using pulsed lasers without physical contact between instrumentation transducer. removes some practical impediments traditional piezoelectric architectures (such as wiring) allows devices be placed...

Microrheology, the study of fluids on micron length-scales, promises to reveal insights into cellular biology, including mechanical biomarkers disease and interplay between biomechanics function. Here a minimally-invasive passive microrheology technique is applied individual living cells by chemically binding bead surface cell, observing mean squared displacement at timescales ranging from milliseconds 100s seconds. Measurements are repeated over course hours, presented alongside analysis...

The single cell eukaryotic protozoan Acanthamoeba castellanii exhibits a remarkable ability to switch from vegetative trophozoite stage cystic form, in response stressors. This phenotypic involves changes gene expression and synthesis of the wall, which affects organism resist biocides chemotherapeutic medicines. Given that encystation is fundamental survival mechanism life cycle A. castellanii, understanding this process should have significant environmental medical implications. In present...

Brillouin light scattering (BLS) is an emerging method for cell imaging and characterisation. It allows elasticity-related contrast, optical resolution label-free operation. Phonon microscopy detects BLS from laser generated coherent phonon fields to offer attractive route since, at GHz frequencies, the wavelength sub-optical. Using image single cells challenging as signal noise ratio acquisition time are often poor. However, recent advances in instrumentation have enabled of fixed living...

In this paper we demonstrate a new scheme for optical super-resolution, inspired, in-part, by PALM and STORM. each object in the field of view is tagged with signal that allows them to be detected separately. By doing can identify locate separately significantly higher resolution than diffraction limit. We imaging nanoparticles smaller case "tag" have used frequency vibration nanoscale "bells" made metallic whose acoustic vibrational multi-GHz range. Since particles easily excited directly...

In this paper, we show for the first time polarization-sensitive super-resolution phononic reconstruction of multiple nanostructures in a liquid environment by overcoming diffraction limit optical system (1 μm). By using time-resolved pump-probe spectroscopy, measure acoustic signature nanospheres and nanorods at different polarizations. This enables size, position, orientation characterization nanoparticles single point spread function with precision 5 nm, 3 1.4°, respectively. Unlike...

We report results of transient two-wave mixing (TWM) in Er-doped fibers with saturable absorption a linear configuration an adaptive interferometric vibrometer essentially different powers recording waves. The TWM signal modulation depth detected the weak (reflected) wave was shown to be twice as strong symmetric equal powers. In accordance theoretical predictions, experimentally observed amplitude grew continuously fiber optical density whole investigated range alpha(0)L approximately...

Understanding the mechanical properties of biological cells is a challenging problem for life sciences partly because there are limited methods mapping elasticity with high resolution. Phonon microscopy form Brillouin light scattering which uses coherent phonons imaging elasticity-related contrast, phonon resolution and without labels. It can measure material such as sound velocity, acoustic impedance attenuation. To use it contrast mechanism in microscopy, numerical aperture (NA) lenses key...

This report introduces a novel time resolved Brillouin spectrometer, consisting of an opto-acoustic transducer which resides on the tip single-mode optical fiber arbitrary length with 125 μm outer diameter and 5 sensing diameter. Demonstrated here are proof concept spectroscopic measurements - shifts in frequency sensitivities 41±3MHz/%wt 2.5±0.6 MHz/°C for changes water-salinity water-temperature, respectively, interpolated resolution 9±2 MHz. The technique benefits from low-cost raw...

The optical resonance of metal nanoparticles can be used to enhance the generation and detection their main vibrational mode. In this work, we show that method allows accurate characterisation particle’s size because frequency plasmonic only depends on mechanical properties. Moreover, by a careful selection particle and/or probe laser wavelength, detected signal increased large factor (∼9 for particles in work) under same illumination conditions. Finally, experimentally different sizes...

Reconstruction of nanostructure sizes and shapes by measuring their acoustic vibrations.

Abstract There is a consensus about the strong correlation between elasticity of cells and tissue their normal, dysplastic, cancerous states. However, developments in cell mechanics have not seen significant progress clinical applications. In this work, we explore possibility using phonon acoustics for purpose. We used microscopy to obtain measure elastic properties normal breast cells. Utilising raw time-resolved phonon-derived data (300 k individual inputs), employed deep learning...

Mechanical imaging and characterisation of biological cells has been a subject interest for the last twenty years. Ultrasonic based on scanning acoustic microscope (SAM) mechanical probing have extensively reported. Large attenuation at high frequencies use conventional piezo-electric transducers limit operational frequency SAM. This limitation results in lower resolution compared to an optical microscope. Direct form applied stress by contacting probes causes exhibits poor depth resolution....

In this paper, we show a proof-of-concept method to parallelise phonon microscopy measurements for cell elasticity imaging by demonstrating 3-fold increase in acquisition speed which is limited current hardware. Phonon based on time-resolved Brillouin scattering, uses pump–probe with asynchronous optical sampling (ASOPS) generate and detect coherent phonons. This enables access the via frequency sub-optical axial resolution. Although systems ASOPS are typically faster compared ones built...

In order to realise the clinical potential of Brillouin scattering-based techniques, it is critical develop an endoscopic probe for measuring elasticity in future in-vivo environments. We have developed a phonon which actively injects high amplitude GHz strain pulses into specimens and demonstrated proof concept this technique can be used resolution 3D imaging. talk we show that new technology highly applicable imaging biological tissue from single-cell scale multi-cellular organisms...

Cancer remains one of the most important contributors to premature mortality at global level. The elastic properties cells and tissue have been shown correlate with normal, dysplastic, cancerous states. In this work, we rely on time-resolved Brillouin scattering characterise normal contrast provided by their properties. doing so, achieved proof concept that artificial intelligence can be used differentiate between cell lines a low number highly localised measurements. A differentiation...

Advances in artificial intelligence (AI) show great potential revealing underlying information from phonon microscopy (high-frequency ultrasound) data to identify cancerous cells. However, this technology suffers the 'batch effect' that comes unavoidable technical variations between each experiment, creating confounding variables AI model may inadvertently learn. We therefore present a multi-task conditional neural network framework simultaneously achieve inter-batch calibration, by removing...