In the field of in vitro fertilisation (IVF), there is a need to understand how cell properties of the cumulus oocyte complex may be used to predict successful pregnancy and live birth rates post-IVF. Here we used optical tweezers for the first time to measure the viscosity of the cumulus cell matrix surrounding the oocyte (egg). This study aimed to determine whether the viscosity of the cumulus cell matrix – prior to fertilisation – is reflective of subsequent embryo developmental potential and indicative of pregnancy success.
Measurements were performed using a 1µm diameter silica probe particle trapped by a focused 1064nm laser. We benchmarked the accuracy of the system by measuring the viscosity of glycerol with varying mass fractions. Viscosity measurements of the cumulus cell matrix were performed in isolation from both the cumulus cells and the oocyte. This showed that the viscosity of cumulus matrix was significantly higher when sampled from oocytes with a higher developmental potential (in vivo matured) compared to those of lower quality (in vitro matured).
Highly multi-mode media convert a coherent input field’s spatial profile into a granular speckle patterns. These speckle patterns are heavily dependent upon properties of the multi-mode medium and the input light field. Examining these speckle patterns enables extraction of these parameters; numerous spectrometers have been demonstrated by analyzing speckle. This is germane to precision measurement of optical wavelength, which is crucial in many applications including: laser spectroscopy, optical sensing, and laser locking. To the best of our knowledge we have demonstrated, for the first time, a transmission matrix method (TMM) speckle spectrometer capable of resolving the hyperfine structure of rubidium at 780nm. We compare this with other TMM speckle spectrometers in literature as well as discussing the advantages and disadvantages of the transmission matrix technique.
Understanding the mineralogy of the Moon is key to viable mining and mineral processing necessary for the utilization of resources on the lunar surface. As on Earth, the minerals present in a resource can have drastically different physical and chemical properties, and require varying processing protocols to extract useful materials. The mineralogical and chemical complexity of lunar material requires more detailed analysis than simple observation of the elemental composition for detailed scientific understanding, or successful resource extraction. However, traditional non-contact sensing suffers from either low spatial resolution, or the inability to collect data fast enough to enable real-time decision making. Real-time data facilitates selective mining of target minerals of interest, and the optimization of mineral feeds consistent, high yields of extracted resources. Fluorescence analysis can obtain detailed mineralogical information at a high spatial resolution, while still being able to analyze bulk areas at speeds rapid enough such that precise mining or mineral processing control operations can occur. Useful fluorescence from minerals does occur, especially in the near-infrared (NIR), with these ‘novel fluorescence’ peaks standing out in an otherwise low-background emission waveband range, and are additionally enhanced at cold temperatures. This is demonstrated through the detection of NIR fluorescence discovered from specific minerals important for metal, oxygen, and water extraction on the lunar surface. The practical implementation of sensing devices utilizing this novel fluorescence is discussed, showing that simple and reliable systems can be designed which locate high-value lunar minerals in real-time with minimal data processing or deconvolution required.
Volumetric 3D display allows a wide range of applications in air traffic control, medical imaging, automotive and aerospace design, visualisation in weather or defence monitoring. Previous work in this area has examined the use of upconversion in low-phonon-energy fluoride glasses and single crystals as the imaging chamber material. However, these glasses and crystals are difficult to produce at a sufficient size and quality. We will report on our examination of a range of low-phonon-energy glasses. This study identified tellurite glass as a promising candidate with high fluorescence efficiency for display and up-scalability of the imaging chamber size.
An innovative mid-infrared polarization-maintaining photonic crystal fiber (PM-PCF) with an asymmetric orthogonal pattern of longitudinal holes having different periods and diameters is presented. The PM-PCF is designed and made of chalcogenide glass to offer endlessly single mode in the mid-infrared (2-6μm) with good beam quality (M2~1). Most importantly, the guided mode is circular to improve the coupling efficiency and to perfectly collimate the output beam with a single lens. The large mode area enables the transmission of high-power polarized infrared laser (<10W CW). Also, the new PM-PCF has high birefringence (~10-4), low propagation losses (0.2dB/m), and low insertion loss (<0.1dB). The PM-PCF preform is made by extrusion and is used to draw the mid-infrared PM-PCF. Simulation and experimental results on the mid-infrared PM-PCF are presented.
Nanoscale thermometry of biological systems offers new insights into cell metabolism at a sub-cellular scale. Currently, there is no way in which we can achieve high resolution temperature sensing on these systems without the use of foreign materials such as biological markers. Using rare-earth doped tellurite glass as a platform for thermometry, we report micron scale scale temperature sensing via confocal scanning microscopy. We demonstrate this technique by monitoring the cooling from a water droplet and report a net temperature change of 7.04K with a sensitivity of 0.12K. These results pave the way for “marker free” micron scale temperature sensing in biological systems.
The ability to perform spatially resolved measurement of extreme temperatures, the order of 1000°C and above, would yield enormous benefit to many heavy industrial processes. While optical fibers can provide spatial information along their length through distributed and multi-point sensing techniques, operation at such temperatures is an area of ongoing research and development. A challenge is that conventional optical fibers, fabricated with a chemically doped core, suffer dopant diffusion at these high temperatures, ultimately limiting their operating lifespan. We can overcome this limitation by using specialty pure silica glass fibers, such as microstructured optical fibers. In this work we demonstrate the ability to use such fibers in a significantly multiplexed configuration with twenty fiber Bragg grating sensing elements written via femtosecond laser ablation.
This paper reports on a multi-point optical fiber pressure sensor using fiber Bragg gratings (FBGs) written on an exposed core optical fiber (ECF) by femtosecond laser. The pressure sensing elements were constructed as Fabry-Perot (FP) interferometers of different cavity lengths using pairs of FBGs with identical resonant wavelength. In this fashion an interference pattern was formed within the FBG bandwidth with much narrower fringes, leading to better detection limit. Fast Fourier transform (FFT) was used to calculate the phase change of the FP interference pattern with respect to applied pressure. The pressure sensitivity was proportional to the cavity FP cavity length, and reached -0.672 rad/MPa for the case of FP with 9 mm cavity length. The proposed sensor has potential to measure pressure at very high temperature thanks to its single material configuration.
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.
Hollow core fibers (HCFs) have found extensive use for biological sensing applications, with areas such as Raman spectroscopy being of key interest for deployment of these fibers due to their low Raman background and broad transmission spectral windows. However, fabrication of these fibers is currently based on capillary stacking of hollow tubes, a complex, time-consuming and therefore costly process that limits their potential for use in practical devices.
Glass billet extrusion, an alternative to the capillary stacking process, presents a potential pathway to reducing the high fabrication cost of HCFs. Extrusion is a process in which a glass billet is heated to its softening point and is then forced through a metallic die containing the inverse of the desired structure. This is a one-step, automated process that requires no manual stacking to obtain the desired glass preform.
Initial work using extrusion for HCF fabrication has resulted in fibers with large variations in the uniformity of the core walls, leading to increases in the optical loss of these fibers over the theoretical predictions. Here we present work on improvements to the extrusion process of these fibers, aiming to both reduce the loss of the fibers. Several iterations of the die exit geometry are shown to affect the geometry and uniformity of the preform structure, which translates into changes in the final fiber geometry and therefore the transmission properties of the HCFs. The fabrication methods used here show strong potential for improved guidance properties in future generations of HCFs.
We report the development of an optical fibre probe which could find use as an aid for margin detection during surgery. A fluorophore doped polymer is coated on an optical fibre tip, allowing for pH values of unknown tissue to be measured and compared to healthy tissue, to discriminate between healthy and cancerous tissue.
This probe is integrated within a portable system, requiring no alignment or access to specialised vibration damped optical tables. A miniature spectrometer allows for measurements to be performed on-site, opening up the potential for use of these probes within the operating theatre for in-vivo measurements.
Reactive Oxygen Species (ROS) cause DNA damage and defective function in sperm and also affects the developmental competence of embryos. It is therefore critical to monitor ROS in sperm, oocytes and developing embryos. In particular, hydrogen peroxide (H2O2) is a ROS important to normal cell function and signalling as well as its role in oxidative stress. Here we report the development of a fluorescent sensor for H2O2 using carboxyperoxyfluor-1 (CPF1) in solution and attached to a glass slide or multi-mode optical fibre. CPF1 increases in fluorescence upon reaction with H2O2 to non-invasively detect H2O2 near developing embryos. These probes are constructed by immobilising CPF1 to the optical fibre tip a polyacrylamide layer. Also reported is a new dual optical fibre sensor for detecting both H2O2 and pH that is functional at biologically concentrations of H2O2 and can sense pH to 0.1 units. This research shows promise for the use of optical fibre sensors for monitoring the health of developing embryos. Furthermore, these sensors are applicable for use beyond embryos such as detecting stress in endothelial cells involved in cardiovascular dysfunction.
Vitamin B12 (cobalamin and its derivatives) deficiency has been identified as a potential modifiable risk factor for dementia and Alzheimer’s disease. Chronic deficiency of vitamin B12 has been significantly associated with an increased risk of cognitive decline. An effective and efficient method for measuring vitamin B12 concentration in human blood would enable ongoing tracking and assessment of this potential modifiable risk factor. In this work we present an optical sensor based on resonance Raman spectroscopy for rapid measurements of vitamin B12 in human blood serum. The measurement takes less than a minute and requires minimum preparation (centrifuging) of the collected blood samples.
Optical fiber sensors for Raman spectroscopy based on hollow core optical fibers have shown great promise due to their low glass background, and high signal collection efficiency. We have previously demonstrated how glass billet extrusion can be used to make simplified hollow core fibers based on a single suspended ring. In this work we investigate the performance of these optical fibers as sensors for Raman spectroscopy. These fibers are used to excite samples at a range of laser excitation wavelengths to scan across the transmission profile of the optical fibers, allowing comparison of the performance of these fibers against commercially-available alternatives.
Incomplete removal of malignant tumours continues to be a significant issue in cancer surgery. It increases the risk of local recurrence and impaired survival, and results in the need for additional surgery with associated attendant costs and morbidity. While pathological methods exist to determine tissue type during surgery, these methods can compromise post-operative pathology, have a lag of minutes to hours before the surgeon receives the results of the tissue analysis and are restricted to excised tissue.
In this work we report the development of an optical fibre probe which could find use as an aid for margin detection during surgery. A fluorophore doped polymer coating is deposited on the tip of an optical fibre, which can then be used to record the pH by monitoring the emission spectra from the embedded indicator. The pH values of unknown tissue are measured and compared to healthy tissue, allowing for discrimination between healthy and cancerous tissue.
The probe developed here shows strong potential for use during surgery, as the probe design can be readily adapted to a low-cost portable configuration which could find use in the operating theatre. Use of this probe in surgery either on excised or in-vivo tissue has the potential to improve success rates for complete removal of cancers.
KEYWORDS: Optical fibers, In vivo imaging, Brain, Temperature metrology, Biomedical optics, Body temperature, Glasses, Luminescence, Optical testing, Optical alignment
We report on the development of an optical fiber based probe for in vivo measurements of brain temperature. By using a thin layer of rare-earth doped tellurite glass on the tip of a silica optical fiber a durable probe, suitable for long-term in vivo measurements of temperature can be fabricated. The probe can be interrogated using a portable optical measurement setup, allowing for measurements to be performed outside of standard optical laboratories as no alignment of components is required. This setup is deployed to a medical research laboratory to show preliminary results on the use of these optical fibers for in vivo pre-clinical measurements of brain temperature.
Surgery on tumours commonly involves a lumpectomy method, where a section of tissue containing the tumour is removed, to improve cosmetic outcomes and quality of life. Following surgery, the margins of the removed section are checked by pathology tests to ensure that the entire tumour has been removed. Unfortunately, approximately 15-20% of margins show incomplete removal and require a subsequent operation to remove the remaining tumour. Tumour detection during surgery could allow the removed section to be enlarged appropriately, reducing the likelihood of requiring subsequent surgery. A change in the extracellular pH in the vicinity of a tumour, when compared to normal tissue, has been shown previously in literature. We have fabricated an optical fibre tip pH sensor by embedding a fluorophore within a photopolymerised acrylamide polymer on the tip of a 200 micron diameter silica fibre. Preliminary measurements of human melanoma samples have shown a significant difference in the measured pH values between tumour and normal tissue. This demonstration paves to way to highly accurate margin detection during surgery.
The production of reactive oxygen species (ROS) is known to affect the developmental competence of embryos. Hydrogen peroxide (H2O2) an important reactive oxygen species, is also known to causes DNA damage and defective sperm function. Current techniques require incubating a developing embryo with an organic fluorophore which is potentially hazardous for the embryo. What we need is a localised ROS sensor which does not require fluorophores in solution and hence will allow continuous monitoring of H2O2 production without adversely affect the development of the embryo. Here we report studies on such a fibre-based sensor for the detection of H2O2 that uses a surface-bound aryl boronate fluorophore carboxyperoxyfluor-1(CPF1). Optical fibres present a unique platform due to desirable characteristics as dip sensors in biological solutions. Attempts to functionalise the fibre tips using polyelectrolyte layers and (3-aminopropyl)triethoxysilane (APTES) coatings resulted in a limited signal and poor fluorescent response to H2O2 due to a low tip surface density of the fluorophore. To increase the surface density, CPF1 was integrated into a polymer matrix formed on the fibre tip by a UV-catalysed polymerisation process of acrylamide onto a methacrylate silane layer. The polyacrylamide containing CPF1 gave a much higher surface density than previous surface attachment methods and the sensor was found to effectively detect H2O2. Using this method, biologically relevant concentrations of H2O2 were detected, enabling remote sensing studies into ROS releases from embryos throughout early development.
We report here on the development of a method to induce a stroke in a specific location within a mouse brain through the use of an optical fibre. By capturing the emitted fluorescence signal generated using the same fibre it is then possible to monitor photochemical changes within the brain in real-time, potentially reducing the requirement for post-operative histology to determine if a stroke has successfully been induced within the animal.
We report on the development of a point temperature sensor, based on coating tellurite onto the tips of optical fibres. By doping the tellurite glass with rare earth ions such as erbium the tip of the fibre can act as a localized temperature sensor by monitoring the upconversion emission from the ions. This sensing geometry allows the temperature to be measured with good spatial resolution, while the strong response of the rare earth ions to changing temperature provides a temperature precision of 0.1-0.3 °C over the measured range.
Rare-earth doped upconversion nanocrystals are emerging as the next-generation luminescent biomaterials. Here we load
NaYF4: Yb/Er and NaYF4: Yb/Tm upconversion nanocrystals into a soft-glass suspended-core optical fiber dip sensor,
allowing sensitive measurements and power-dependent characterizations to be performed. This, in combination with
negligible background autofluorescence from the glass fiber when using infrared excitation has provided a significant
improvement in terms of sensitivity over what has previously been demonstrated using an optical fiber dip sensor.
For detection we employ suspended-core optical fibers, which have found extensive use in sensing applications. These
combine the high evanescent overlap comparable to that of a nanowire, with the robust handling characteristics and long
interaction length of a conventional fiber. The fiber sensor platform allows measurements to be performed using minimal
sample volumes (<20 nL) while still maintaining the sensitivity of the platform.
We investigate a powerful new sensing platform based on upconversion luminescence in NaYF4:
Yb/Er nanocrystals loaded inside a suspended-core microstructured optical fibre. The use of a NIR
source enables autofluorescence from the glass to be reduced compared to using visible sources for
excitation of fluorescence. We demonstrate a substantial improvement in the detection limit that can be
achieved in a suspended-core fibre sensor, with detection limits as low as 660 fM achieved. This is a
factor of 15× better than the best results previously reported using Quantum dots in a similar fibre.
Optical fibers are ideal for environmental sensing applications because of their ability to transmit optical signals to
and from the sensing region without the use of free-space optics. By accessing the evanescent field, the fiber itself can
act as the sensing element and long interaction lengths can be achieved. Microstructured optical fibers are particularly
suited to such applications as the species of interest can occupy the air spaces within the fiber.
Here we use a suspended nanowire design that provides the high evanescent overlap of a nanowire with the long
interaction length and robustness of a conventional fiber. The fluorescence-detection approach proposed in this paper is
attractive because of its simplicity. When one end of the fiber is dipped into the sample, capillary forces draw the liquid
into the voids within the fiber. The evanescent field of the pump light excites the fluorescent labels and a portion of the
fluorescence is captured by the fiber core and propagates to the fiber tips.
The aim of this work is to improve the sensing architecture to increase the sensitivity of the sensor, and to examine
the primary factors such as the background glass fluorescence currently restricting the detection limit in this type of
sensor. This work is focused on biological detection in liquid samples using Quantum dots, but through careful selection
of the fluorescent dye this can be extended to a large number of alternative applications. Using this system we are able to
detect quantum dot concentrations as low as 10 pM.
The ability to measure the concentration of hydrogen peroxide (H2O2) in solution is critical for quality assessment and
control in many disparate applications, including wine, aviation fuels and IVF. The objective of this research is to
develop a rapid test for the hydrogen peroxide content that can be performed on very low volume samples (i.e. sub-μL)
that is relatively independent of other products within the sample.
For H2O2 detection we use suspended core optical fibers to achieve a high evanescent field interaction with the fluid of
interest, without the constraint of limited interaction length that is generally inherent with nanowire structures. By filling
the holes of the fiber with an analyte/fluorophore solution we seek to create a quick and effective sensor that should
enable detection of desired species within liquid media. By choosing a fluorophore that reacts with our target species to
produce an increase in fluorescence, we can correlate observed fluorescence intensity with the concentration of the target
molecule.
We present improvements to fluorescence sensing in microstructured optical fibers that result in significantly
improved sensitivity relative to previously published results. Concentrations of CdSe quantum dots down to 10 pM
levels have been demonstrated. We show that the primary limitation to the sensitivity of these systems is the
intrinsic fluorescence of the glass itself. We investigate alternative architectures for improved sensitivity by
separating the excitation and capture in to separate cores within a single fiber
We demonstrate a new detection limit for fluorescent species in small-core glass microstructured optical fibres. Two
detection schemes are explored: forward detection by an optical spectrum analyser; and backward detection by a
photodiode. In the second scheme, characterisation of the fluorescence signal during fibre filling allows us to accurately
separate quantum-dot fluorescence from intrinsic glass fluorescence. The spectral overlap of these two fluorescence
sources is the principal limit to the detection sensitivity. We demonstrate a detection limit of ~200 pM.
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