This PDF file contains the front matter associated with SPIE Proceedings Volume 11202, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

We have seen great advances in photonics based methods for imaging and manipulation. However whislt improvements have been seen in beating the diffraction limit and gaining wide field imaging, imaging through scattering media remains a challenge. I will describe approaches that tackle this issue. In particular I will describe using a geometry where the excitation beam is orthogonal to the detection arm of the optical system has come to the fore. This method is known as light sheet imaging or selective plane illumination microscopy. This talk will describe the basic premises of this field and highlight how we may increase penetration using propagation invariant Bessel and Airy beams as well as multiphoton imaging, including particularly three photon excitation. In the second part of my talk I will move to an epi-fluorescent geometry and describe the use of temporal focusing with single pixel detection. This scheme which we term TRAFIX can image through turbid media without prior knowledge of the scattering properties present and can be implemented on both two and three photon imaging.

Compressed ultrafast photography (CUP) is a new imaging technique which incorporates the high-speed imaging capabilities of a streak camera with principles from compressed sensing to allow for single-shot, ultrafast imaging of optical phenomena at up to 100 billion frames per second¹. While this technique has primarily been utilized to observe physical phenomena, it has broad ranging application to biological imaging including fluorescence lifetime microscopy, and single-shot hyperspectral imaging². Additionally, similar optical systems can be used to for streak camera microscopy (SCM), enabling the resolution of sub microsecond changes in cellular membrane potential in response to electrical stimulation³. Here, we present several applications for CUP based imaging and spectroscopy as a novel tool to enable more rapid biological imaging and sensing.

Living cells adjust their cytoskeletal organization and mechanically change their overall shape by reacting to the changes of the microenvironment. The ability to quantify these dynamic events in micro and nanoscale in real-time at the same time contributes to our understanding of the functional response of living cells. The combination to achieve both microscale and nanoscale imaging simultaneous at volumetric speeds is challenging. Traditional TIRF microscopy has excelled in measuring surface interaction but yet limited in imaging depth and requires fluorescent labelling. Likewise, the ability to quantify the total volume and shape change of biological cells as they interact requires either confocal microscopy or lightsheet microscopy. In this paper, we propose an in toto label free approach through coherent optical interference to measure volumetric information and surface interaction at the same time to provide a full view of the cell during dynamic activities.

Live cell imaging is challenging because the difficult balance of maintaining both cell viability and high signal to noise ratio throughout the entire imaging duration. Label free quantitative light microscopy techniques are powerful tools to image the volumetric activities in living cellular and sub-cellular biological systems, however there are minimal ways to identify phototoxicity. In this paper, we investigate the use of neural network to restore quantitative digital hologram micrographs at ultra-low light levels down to 0.06 𝑚𝑊/𝑐𝑚² which approximately two orders of magnitude lower than sunlight. By developing an adaptive image restoration method specifically tailored for digital holograms, we demonstrated the 2x improvement in SSIM over existing denoising methods. This demonstration could open up new avenues for high resolution holographic microscopy using deep ultraviolet coherent sources and achieve high-resolution imaging with ultralow light illumination.

Localized surface plasmon resonance (LSPR) is a subwavelength optical phenomenon that has found widespread use in bio- and chemical- sensing applications thanks to the possibility to efficiently transduce refractive index changes into wavelength shifts. However, is it very hard to transpose the successes demonstrated in liquid and physiological environment toward the detection of gasous molecules. In fact, the latter typically adsorb in an unspecific manner and induce very minute refractive index changes tipicaly below the sensor sensitivity.

Here, we show first insights on the aerosol large-scale self-assembly of metasurfaces made of monocrystalline Au nanoislands with uniform disorder over large scale. Notably, these architectures show tuneable disorder levels and demonstrate high-quality LSPR, enabling the fabrication of highly performing optical gas sensors detecting down to 10−5 variations in refractive index.

Next, we use our aerosol synthesis method to integrate tailored fractals of dielectric TiO2 nanoparticles onto resonant plasmonic metasurfaces. We show how this integration strongly enhances the interaction between the plasmonic field and volatile organic molecules and provides a means for their selective detection. Interesting, the improved performance is the result of a synergetic behavior between the dielectric fractals and the plasmonic metasurface: in fact, upon this integration, the enhancement of plasmonic field is drastically extended, all the way up to a maximum thickness of 1.8 μm.

Optimal dielectric-plasmonic structures allow measurements of changes in the refractive index of the gas mixture down to <8x10^-6 at room temperature and selective identification of three exemplary volatile organic compounds (VOCs). These findings provide a basis for the development of a novel family of hybrid dielectric-plasmonic materials with application extending from light harvesting and photo-catalysts to contactless sensors for non-invasive medical diagnostics.

In this contribution, we show how the stability and ease-of-use of an integrated interferometric photonic biosensor platform can be enhanced using optical frequency combs, without any necessary changes to the sensor chip design. We show that if the comb line spacing of the optical frequency comb is adjusted to be at 120° intervals of the periodic spectral response of the used Mach-Zehnder interferometer and the transmission power values of the three comb lines are recorded over time, it is possible to extract the interferometer phase linearly and continuously for every sample point. This measurement approach provides an accurate phase measurement and is independent of the interferometer bias. Furthermore, it is robust against intensity fluctuations which are common to all three used comb lines. Our demonstration uses a simple silicon photonic interferometric refractive index sensor, and we show that the benefits of our approach can be achieved without degrading the lower limit of detection of 3.70×10^-7 RIU of our sensor platform. Our technique can be applied to any interferometric sensor and only requires a single input and single output and does not need any special couplers. This technique offers a drop-in replacement to the commonly used single wavelength phase measurement.

Ultimately, this research is to develop a versatile 3D non-axial finite element model of the whole human eye that is not limited to any specific ophthalmic treatment. The goal is to include the asymmetric cooling by an equivalent uniform layer representing the vascular system of the choroid. In this paper, we trialled the feasibility of simulating conductive heat transfer through the retina as the base step towards a 3D model. This was done by developing a 2D axial model of the retina in which most heat is absorbed in the retinal pigment epithelium.

Motion artefacts in traditional scanning spot optical coherence tomography (OCT) anterior-segment imaging can hamper the application of OCT to the determination of refractive properties of ocular interfaces. To overcome this problem, we have developed a Hyperparallel spectral domain approach (HP-OCT) for high speed volumetric imaging (up to 300k Ascan/ s). We demonstrate a repeatability of better than 0.1 Diopters for in-vivo anterior and posterior corneal power measurements as well as providing biometric measurements such as axial length, pachymetry, lens thickness and curvature, anterior chamber depth and axial length.

We have demonstrated that an optical fibre-based pH sensor can be utilised to accurately assess pH in a biological environment. Initial measurements were performed on 5 μL drops of culture medium containing individual female mouse reproductive cells (cumulus-oocyte-complexes, COCs), with the goal of obtaining a biomarker of individual cell health during assisted reproductive processes. Improvements to the measurement procedure were found to reduce fluorescence signal variability, enabling improved measurement precision compared to previous studies. Results show the application of treatments which serve to increase lactic acid production by the COC, and thus induce an acidification of the local microenvironment, are detectable by the pH sensor. This optical technology presents a promising platform for the measurement of pH and the detection of other extracellular biomarkers to assess cell health during assisted reproduction.

We demonstrate in-vivo chemical sensing using silk-coated exposed-core microstructured optical fibers (ECFs). The ECF provides advantages in sensitivity due to the direct access of the fiber core to the surrounding environment with integrated measurement along the entire fiber length, rather than simply the fiber tip as is common in other probes. The silk coating provides an encapsulation of the sensor molecules, and is well known as a biocompatible material. This deployable fiber sensor is fabricated with simple splicing and coating techniques, making it practical to be used in a range of biomedical sensing applications, which we demonstrate through pH sensing in a mouse model.

Fluorescent nanodiamonds made from high-pressure high-temperature diamond are increasingly used in biological imaging and sensing applications. To date, only red and green fluorescent nanodiamonds are widely available, severely limiting nanodiamond-based multiplexed imaging. Here, we report on recent progress in the fabrication and characterization of fluorescent nanodiamonds with fluorescence colors from 450 nm to 900 nm. The fluorescence originates from a range of fluorescent color centers based on nitrogen, silicon, nickel and vacancy defects in the diamond lattice. The optical properties of these color centers in diamond nanoparticles are discussed in detail and the utility of nanodiamond-based multiplexed bioimaging demonstrated in experiments in-vitro.

The UV-C band ultraviolet light irradiation is one of the most commonly used ways of disinfecting water contaminated by pathogens such as bacteria and viruses. Sonoluminescence, the emission of light from acoustically-induced collapse of air bubbles in water, is an efficient means of generating UV-C light. However, because a spherical bubble collapsing in the bulk of water creates isotropic radiation, the fluence of the generated UV-C radiation is insufficient for disinfection. Here, we theoretically demonstrate that we can create a UV light beam from aspherical air bubble collapse near a gallium-based liquid-metal microparticle. The beam is perpendicular to the metal surface and is caused by the interaction of sonoluminescence light with UV plasmon modes in the metal. We calculate that such beams are capable of generating UV-C fluences exceeding 10mJ/cm², which is sufficient to irreversibly inactivate 99.9% of pathogens in water with the turbidity of more than 5NTU.

Despite its wide-spread use, the success rate of assisted reproductive technologies including in vitro fertilization is less than 20%. Most human embryos are mosaic for chromosome abnormalities: containing cells that are euploid (normal) and aneuploid (incorrect number of chromosomes). Currently, a cell biopsy is used in IVF clinics to diagnose aneuploidy in the embryo but this does not provide a diagnosis of how many cells are aneuploid in the entire embryo. Hence, the development of a non-invasive tool to determine the proportion of aneuploid cells would likely improve IVF success. Aneuploidy in human embryos leads to altered metabolism. The co-factors utilized in cellular metabolism are autofluorescent and can be used to predict the metabolic state of cells. Here we used hyperspectral imaging to noninvasively assess intracellular fluorophores and thus metabolism. In this study, we utilized a powerful model of embryo aneuploidy where we generate mouse embryos with differing ratios of euploid:aneuploid cells. We also used primary human fibroblast cells with known aneuploidies to make comparison with euploid cells. Hyperspectral imaging of 1:3 chimeric embryos showed a distinct spectral profile compare to the control/normal embryos. The abundance of FAD in the inner cell mass (cells that form the fetus) of euploid and aneuploid blastocysts was strikingly different. For human cell lines, we were able to clearly distinguish between euploid and aneuploid with different karyotypes. These data show hyperspectral imaging is able to distinguish cells based on their ploidy status making it a promising tool in assessing embryo mosaicism.

Oxygen metabolism is a necessary process that takes place in animals and plants. Our cells and plant cells produce free radicals known as reactive oxygen species (ROS) continuously as a byproduct of oxygen metabolism and reaction to various environmental stresses, which must be normalized to avoid oxidative stress. Oxidative stress is intimately linked to cellular energy balance and occurs when there’s an imbalance between production and accumulation of ROS in cells and tissues and the ability of a biological system to keep in a redox steady state. We show preliminary results of an optical fiber based reversible in-vivo biosensor for understanding redox balance within living systems. The biosensor measured protein carbonyls (a marker of oxygen metabolism and oxidative stress) in pig-skin, live mouse, and wheat plant.

High precision magnetometry is important for a range of applications from the monitoring of biologically generated magnetic fields (e.g. magnetoencephalography and magnetocardiography), to navigation in GPS denied environments, to the detection of gravitational waves. Diamond containing the negatively-charged nitrogen vacancy colour centre (NV^-) has emerged as a powerful room-temperature sensing solution. Here we explore NV^- centres as a laser medium for a new form of magnetometry: laser threshold magnetometry (LTM). LTM works by placing NV^- inside an optical cavity and uses the coherent laser output as a potentially more sensitive readout channel than is possible using conventional (incoherent) optically detected magnetic resonance. Here we show progress towards LTM with diamond. We show twolaser excitation and stimulated emission in free space, and report progress towards diamond-cavity experiments. Our studies highlight the need for different NV^- optimisation for laser applications, rather than those conventionally used for quantum information applications

We aim to understand how brain circuits, learn, memorize or process information. To achieve this aim, we follow a bottomup approach by focusing on single neurons from rat brains and study how different synaptic inputs of a single neuron translate to an output or an action potential. We have custom-built a unique two-photon laser microscope that incorporates a holographic projector, which transforms the incident laser into multiple foci at the sample volume. The hologram is programmable so we can position the different foci anywhere around the neuron in 3D. Each focus can be used to trigger a synaptic input or used as an optical probe to record the activity of the neuron. We can therefore stimulate and probe the activity from multiple locations within the neuron’s dendritic tree using light. For triggering inputs, a focal stimulation represents a synaptic input via two-photon photolysis of caged neurotransmitters. For recording, a laser focus excites a calcium indicator that changes in fluorescence whenever the neuron is active. Using these techniques, we have now identified a novel function of a specific set of dendrites that can have a significant role in learning and memory. The set of dendrites we are probing are currently unexplored due to their very thin morphology. We were able to observe unique properties that allow these dendrites to be more receptive to inputs whenever the neuron fires a series of action potentials. Hence, they have a functional role in the brain's capacity to learn and memorize.

Since its discovery in the 1970s, surface-enhanced Raman scattering (SERS) has attracted interest as a sensitive technique for detecting a wide range of analytes. However, SERS is a complex physicochemical phenomenon and tends to suffer from poor levels of reproducibility, which has hindered its translation into practical applications. Here we confirm that the low wavenumber pseudoband arising from the interaction between the edge filter and the elastically scattered light from the laser excitation can be used to perform "hotspot" normalisation of SERS spectra. Together with judicious use of resonant Raman scattering and/or careful control of the surface chemistry, this breakthrough in spectral data processing can address many of the challenges encountered when developing a quantitative SERS-based assay.

Visible to near-infrared spectroscopy has been applied for non-invasive assessment of meat freshness. The measurements were done at room temperature with non-frozen pork samples. The absorbance spectra of the main chromophores in meat including oxymyoglobin, water, fat, and protein were different enough to be identified spectrophotometrically. The decreasing trend in absorbance spectra of these components over time can be associated with freshness decay. We used two configurations, fiber-optic probes and integrating sphere, to study their efficiency in meat quality evaluation. In the integrated sphere configuration, the samples experienced an immediate smooth decrease of oxymyoglobin absorbance arising from loss of superficial freshness, while degradation kinetics of water, fat and protein absorbance were detected after about 2.5 hours. In the fiber-optic configuration capable for sensing up to 570-μm depth, the drop in oxymyoglobin absorbance started after 4.5 hours which would affect directly the color of sample associated with freshness.

Polymer microarrays were used as a high-throughput tool to discover optimal polymer matrices with abilities to entrap sensor molecules while displaying good pH sensitivity. The identified lead polymer poly(methyl methacrylate-co-2- (dimethylamino) ethyl acrylate) (PA101) was dip coated, onto the end of an optical-fibre to fabricate a robust, rapidly responding and robust optical fibre pH sensor, which was used to measure subtle pH changes in lung tissue validating its capabilities for biomedical applications.

We report a silicon Mach-Zehnder interferometer biosensor with an integrated microfluidic sample handling for an accurate and timely detection of cardiac troponin. The performance of the photonic biosensor was evaluated in terms of sensitivity, selectivity and reproducibility following the international clinical guidelines for acute myocardial infarction with the obtention of a complete cardiac troponin point-of-care test. We demonstrated that this biosensor was able to selectively detect cardiac troponin within 10 minutes in the ng/mL-μg/mL range with high reproducibility, achieving a limit of detection as low as 3 ng/mL in a direct assay.

Malus (1809) and Beer-Lambert (1729) laws can be combined to separate birefringence and dichroism contributions in IR hyperspectral imaging. This is achieved by using two optically aligned polarisers for the highest transmittance. By rotation sample between the two aligned polarisers, spectra are taken at several angles for a better fit. This method is shown to resolve orientation of sub-diffraction patterns which are ~50 times smaller than the diffraction limit of 5:1 μm (at the wavelength 3.3 μm). Application potential for very different fields ranging from microscopy of bio- and pharmaceutical materials (silk and paracetamol) to satellite imaging of ocean waves with altimeter at K∝ band of 35.75 GHz or 8.39 cm wavelength will be discussed.

This work reports nanodiamond-silk membranes as an optical platform for biosensing and cell growth applications. The hybrid structure was fabricated through electrospinning and mimics a 2D scaffold with high porosity. The negatively charged nitrogen vacancy (NV-) centres in diamond exhibits optically detected magnetic resonance (ODMR), which enables sensing of temperature variations. The NV- centre, as reported in literature, provides a shift of 74 kHz in the ODMR frequency per degree rise in temperature. For our hybrid membranes, we have however observed that the embedded NV- centre provide a greater shift of 95±5 kHz/K in the ODMR frequency. This higher shift in the frequency will result in improved temperature sensitivity enabling the tracking of thermal variations in the biologically relevant window of 25-50 ºC. The thermal conductivity of silk and diamond-silk hybrid will be explored to investigate this enhanced temperature sensing ability of diamond. The hybrid diamond-silk membranes are found to be hydrophilic with a contact angle of (65±2)º. The biocompatibility of the membranes is tested both in vitro in skin keratinocyte (HaCaT) cells and in vivo in a live mouse wound model. The membranes did not induce any toxicity to the cell growth and survival. Moreover, we observed resistance towards the growth and attachment of bacteria.

Nanodiamonds containing the Nitrogen-vacancy (NV) centre are emerging as a unique platform for nanoscale sensing in biological systems. There is particular interest in the capability of sensing subcellular changes of magnetic and electrical fields, temperature, and pressure. However, the sensitivity of such nanodiamond particles with NV centre as a probe is highly dependent on the relative location and polarisation of the NV centre to the bulk of the particle. Here we show the optical scattering from an NV centre in a nanodiamond as a function of position and orientation within the nanodiamond. The scattering fields are obtained by using the recently developed robust non-singular surface integral equation method.^{1, 2} Our results highlight a new pathway to nanodiamond characterisation which may be useful in teasing out the various effects of surface morphology, surface termination, and formation details, which ultimately may benefit the optimisation of diamond production for nanoscale biosensing applications.

In this study, we have simulated the effect of light sources with different spectral output functions on the generation of A-scans in optical coherence tomography using a fundamental physics-based interferometric model. Many different source function were examined, and compared to a standard Gaussian source. These sources included truncated Gaussians, multiple Gaussians, other non-Gaussian, Lorentzian, square and triangular sources. Only the pure Gaussian source produced A-scans without false artefacts such as satellite peaks, that could produce misinterpretation of real OCT images that may be used for patient diagnosis. A triangular source produces the next best response with small extraneous peaks, whereas all other sources have significant false artefacts present in their A-scans.

Fluorescence recovery after photobleaching (FRAP) has been developed to measure molecular diffusion in living cells. However, conventional FRAP using a single stationary beam guided by a pair of galvanometer mirrors is not tailored for raster scanning microscopy. Furthermore, it has been shown that a single point of 2D FRAP only acquires molecular diffusion within a given imaging plane and does not fully capture the full molecular dynamics. Here, we address these limitations with a custom-built 2-photon polygon scanning microscope that features volumetric scanning with a frame rate of 20 fps and 170 nm pixel size. Importantly, our system allows photomanipulation to selectively measure FRAP from the diffusion dynamics of fluorescent molecules in a 3D sample. To demonstrate these capabilities, we performed rapid axial scans of fluorescent beads in suspension, achieving a volumetric scan rate of less than a second. FRAP functionality was verified in vitro on sulforhodamine-labelled giant unilamellar vesicles and diffusion kinetics determined from the rate of fluorescence recovery. The resolution and speed introduced from polygon scanning microscopy coupled with photomanipulation capabilities sets a precedent for 2-photon 3D FRAP imaging.

Digital Holographic Microscopy (DHM) has emerged as a powerful imaging tool due to its ability to provide quantitative sample morphological data in a label-free manner. Off-axis holography further opens possibilities of numerical approaches to image analysis and data processing. However, this involves computationally heavy workflows that limit the tool’s usability in biomedical research. In this paper, a software package is developed for off-axis hologram reconstruction and processing. The software can perform a variety of bioimaging operations including imaging, region of interest selection, automated reconstruction, and data extraction, with a user-friendly graphical user interface. Originally programmed in MATLAB, the software can be installed to use in common lab-based Microsoft Windows computers. The software can be easily adopted to work with customized off-axis DHM setups, aiming to increase the efficiency of DHM’s bioimaging workflow in the community. To demonstrate this software, blood platelet experiments were conducted to show quantitative volume change of thrombus formation.

In optical micromanipulation, back focal plane interferometry (BFPI) has remained the most widely used method for tracking dielectric and metallic microparticles with nanometer resolution precision at speeds of up to few a MHz. Basic BFPI employs Gaussian beams which severely limits the detection range of the technique unless the focal parameters are tuned by increase the width of the beam, but this is usually concomitant with significant loss in detection sensitivity. A challenge in BFPI is to extend its linear range while maintaining this detection sensitivity along each axis. We constructed a system which utilizes a combination of structured beam shaping and structured detection (Annular Quadrant Detection), which we called Structured Back Focal Plane Interferometry (S-BFPI). A Gaussian beam is shaped by a spatial light modulator by imparting a conical wavefront, which increases the depth of focus while simultaneously maintaining the Gouy phase shift and hence the sensitivity of detection. In addition, an annular QPD is used for detection. Using S-BFPI, we were able to achieve a 200% axial range extension with only a 4.6% reduction in insensitivity, and a 167% lateral range extension with a 45% reduction in sensitivity. SBFPI can tailor its detection range and sensitivity over an intermediate range of displacement and sensitivity improvements at hand. We finally demonstrated its robustness against aberrations common to optical systems. S-BFPI presents itself as a flexible, tunable option for use as an optical measurement tool.

Terahertz (THz) frequency region of the electromagnetic spectrum is defined as radiation of 0.1 to 10.0 x 10¹² Hz (corresponding to wavelengths of 3.0 mm to 0.03 mm). Water in the liquid state has a very high absorption coefficient in the lower THz region¹ (80-350 cm^-1 at 0.1-2.0 THz), with ~90% of the energy being absorbed in the first 0.10 mm at 0.6- 0.9 THz at 35⁰ C. The THz absorption coefficient of ice, on the other hand is only in the order of 1.0 -7.0 cm^-1 in the same range². This, two orders of magnitude difference between the THz absorption of ice and liquid water is a unique feature of the 0.1-2.0 THz range. The water content of most normal tissue, including the dermis and the deeper layers of the epidermis is in the order of 70-73%. The water content of body adipose tissue (fat) is about 20% adults³, thus, freezing the water content in tissues will have a significant influence on THz absorption properties even in adipose tissue. The properties of other, non-water, non-fat components of adipose tissue will also have an influence. The potential for medical imaging or therapeutic intervention at body, room or freezing temperature becomes dependent, in part, on the behavior of the dielectric properties non-water elements of living tissues. These elements have a much lower absorption coefficient, generally in the order of 10-20 cm^-1, and do not change on freezing to the same extent as water^4,5. The preliminary exploration of the concept of the viability of the THz-skin freezing imaging technique in skin was undertaken using computational modelling6. The depth of the dermis in humans is in the range of 2 to 5 mm and thus freezing the skin for examination may involve subcutaneous adipose. It follows that before any advance can be made the temperature dependent properties of adipose tissue need to be understood. One poorly understood aspect is the presence of a phase change in the adipose tissue, analogous to the one observed with butter becoming soft at room temperature, after being firm at refrigerator temperatures (4⁰ C). The attenuated total reflection (ATR) apparatus at the Australian synchrotron provides for a rapid acquisition of data in a temperature controlled environment, with individual sets of readings taking in the order of 1-3 minutes. This provides an appropriate environment for the study of the changes in absorption coefficients in the samples, and to ascertain the utility of ATR for diagnostic applications.

Polycyclic aromatic hydrocarbons (PAHs) are recalcitrant pollutants that can induce carcinogenic, hazardous and mutagenic effects in living organisms. Numerous traditional methods are available for their identification, but these methods require large samples and are time-consuming. In this study we have developed a new method for the determination of PAHs by exploiting their intrinsic fluorescence characteristics. The aim of this research is to investigate real time identification of different PAHs including; Naphthalene, Pyrene and Phenanthrene by using their autofluorescence properties. These pollutants have shown specific optical signatures that are useful for their rapid detection in the contaminated area. In addition to their specific emission spectra, lifetime analysis also can be used to distinguish PAHs with high level of certainty. Our research offers new avenues for real time detection of pollutants.

Cellular imaging in living animal has opened up a wide range of avenues to study cells in its microenvironment. High speed laser scanning microscopy possess the ability to observe fast real-time biological phenomena such as cell movements, cell division, cells death. Due to the anatomical difference of difference organs in small animals, there is a need to engineer a flexible microscope that can readily adapt to different imaging position. For videorate imaging, the design of a flexible microscope depends mainly on scanning devices. Existing multiphoton microscope platforms (i.e. Thorlabs Bergamo® II Series) uses a rotating objective mount to conform of the specimens. This is possible because of the compact resonant mirror scanners. However, for varying imaging speed using a polygon microscope, this approach is not feasible due to high rotating speed. As such, we developed a dual objective microscope system that can achieve both upright and inverted, we termed it as UNI-SCOPE. The integrated platform can achieve flexible scanning speed of up to 120 FPS with an overall footprint of 450mm*600mm*450mm. Using a dual objective approach, users can tailor the platform to the imaging sample.

This paper presents an investigation into a novel electro-optic device for bi-directional brain-machine interface (BMI) by using both a chiral smectic C* liquid crystal to sense neuronal signals and the photovoltaic effect to stimulate neuronal tissues. By leveraging both the optical and electrical domains, this new electro-optic device can achieve high density of channel count and we have so far demonstrated up to 323 such channels. We focus here on tissue stimulation by adding a photovoltaic PN junction into the LC sensing structure described elsewhere to achieve a full bi-directional neuronal interface.

Nerve conduction and activity is a marker of disease and wellness and provides insight into the complex way the nervous system encodes information. We propose an electro-optical detection system and show the recordings from an electrically stimulated in-vitro nerve preparation. The system converts the action potential at the probing position to light intensity before any amplification and detection. Thence the light signal is detected by a photodetector. The new detection system has the ability of isolating the probing point and the amplification circuits, which reduces the electrical interference from the circuit. Moreover, the sampled signal transmitted via optical fibres rather than cables or wires makes it more robust to environmental noise. From the experiment, we demonstrated that the electro-optical detection system is able to detect and amplify the nerve response. By analysing the data, we can distinguish the response from the stimulus artifact and calculate CAP (compound action potential) propagation speed.

Techniques of optical superresolution imaging are vital for uncovering the complex dynamics of biochemistry in cellular environments. However the practical resolution for superresolution imaging is limited by the increased photon budget for superresolution, compared with conventional microscopy. For this reason it is important to determine the optimal methods for analysing all of the incoming information. Most approaches to microscopy use only the wave-like properties of light, but the particle-like nature of light provides extra information that is normally inaccessible and can be used to increase imaging resolution. Here we theoretically study the localisation of quantum emitters using higher-order quantum correlation functions to understand the resolution that is practically achievable for bio-imaging tasks. We show explicit imaging results for varying number of emitters as a function of correlation order to illustrate the necessary tradeoffs between imaging resolution and acquisition time.

Achieving higher resolution scales in optical microscopy allow a more rigorous investigation into the detailed components of cell systems. This higher resolution is typically achieved through super-resolution techniques utilizing methods inside the wave-like nature of light such as point spread function shaping and fluorophore switching. We wish to leverage both particle-like and wave-like natures of light to make a diffraction unlimited protocol. Our protocol uses the well known Hanbury Brown and Twiss (HBT) apparatus in combination with a customized second-order cross-correlation protocol. By performing least squares fitting of the HBT and intensity measurements we obtain diffraction unlimited localization for two particles of unknown relative brightness from few measurement locations. Our results show super-resolution enhancement by an order of magnitude after 5000 detection lifetimes.

The nitrogen-vacancy (NV) centre in diamond is a perfect candidate for quantum sensing applications applied to numerous fields of science. Past studies improved the sensitivity of diamonds containing NV centres by increasing their density or prolonging their coherence time. However, few studies discussed the effects of other defects inside the diamond crystal on the sensitivity of the NV centres. In this study, we demonstrated the implication of single substitutional nitrogen defects on the fluorescence emission, charge state stability, coherence time and sensitivity of the NV centres. We found that there is an optimal concentration of nitrogen defects that allows diamond samples to have a high-density of NV centres and high fluorescence without significantly affecting the coherence time. This results will inform the correct choice of diamond characteristics for current and future quantum sensing applications with the NV centres.

Lanthanide-doped upconversion nanoparticles (UCNPs) are capable of converting near-infrared (NIR) excitation to visible and ultraviolet emission via stepwise multiphoton processes. They offer unique advantages (e.g. sharp emission bands, superb photostability and long lifetimes1) compared to conventional dyes and quantum dots, enabling advanced detection and imaging for biologically important molecules. However, their application to live cells and small animals has been practically limited due to the potential damage under high-power laser illumination, as well as concerns for life scientists who do not necessary possess sufficient knowledge and experience in laser safety. Therefore, we have been exploring new strategies to develop UCNPs that are capable of excitation by incoherent sources such as light-emitting diodes (LEDs), in particular via increased number of sensitizer ions and coating of inert shells.