High-precision microscopic phase imaging without phase unwrapping for cancer cell identification

Hypoxic-ischemia of the brain (tissue oxygen deficiency due to obstructed circulation) during birth can result in neurological impairment and consequently patients that may require specialised care for the remainder of their life. An accurate method for measuring fetal brain oxygenation is therefore required. Traditional clinical techniques do not directly measure cerebral oxygenation and are unpleasant for both the mother and fetus. Near infrared (NIR) spectroscopy is a technique that allows changes in tissue chromophore concentrations to be measured non-invasively. Most NIR spectrometers use algorithms which assume that the optical pathlength of the light in the tissue does not change during the measurement. In the area of fetal NIR spectroscopy, it is of interest to determine whether contraction induced optical pathlength changes produce significant errors in the estimated concentration changes. An intensity modulated optical spectrometer (MOS) can provide optical pathlength information in addition to the pure intensity data provided by traditional NIR spectrometers. An MOS is used here to investigate the influence of contractions on the change in the oxy- and deoxy-hemoglobin status in the fetal brain. It was found that in most cases the changes in optical pathlength did not contribute significantly to any error. It appears that the pathlength changes are primarily due to contraction induced absorption changes. It also appears that artefactual pathlength and absorption changes, which occur due to maternal movement, while to0 complicated to physically characterise are readily recognisable in the raw data.

Researchers at the University of Queensland, Australia, have developed and refined an optical feedback technique for measuring surface roughness. We spoke to one of the authors, Jeremy Herbert, to find out more. Optical feedback interferometry is a non-contact sensing technique that uses a laser as not only a coherent light source, but also as a receiver of information. The beam from the laser is reflected off a target where it is modulated by some property of the material. This light is then reinjected back into the laser cavity where it mixes with the standing wave and disturbs the normal operation of the laser. By monitoring this disturbance through either the output power or the terminal voltage of the laser, information about the target can be determined. Schematic of the roughness measurement experiment showing the direction of translation as parallel to the lasing axis The primary advantage of optical feedback is that a sensor can detect changes in optical path length on the order of nanometres, and/or minute changes in target reflectivity using compact and low cost components; in some configurations, a laser diode is the only optical component. This allows extremely sensitive measurement of quantities such as displacement, velocity and refractive index of transparent media. Another more recent application is the imaging of targets using exotic wavelengths (such as terahertz radiation) for which simple detectors are not widely available. The sensitivity of instrumentation based on optical feedback is a double-edged sword. While this type of sensor can measure minute changes in the properties of the target, it is also very sensitive to changes in environmental parameters such as temperature and vibration. A common approach to minimise the effects of these unwanted influences on the output signal is to perform repeated measurements and average them. Unfortunately in some circumstances, such as the one outlined in the article, it is not possible to perform repeated measurements, and so an alternative strategy is required. Roughness target locations where a focused translating beam would experience higher (green) and lower reflectivity (red). The black arrow shows the direction of scanning. In the article, a method of determining information about the roughness of a surface using optical feedback was described and demonstrated. The method does not rely on repeated measurement, but instead uses the windowed standard deviation of the optical feedback signal to track the effective reflectivity of the surface as it moves. A method to compute the windowed standard deviation in a real-time manner was presented in an earlier article also published in Electronics Letters (Herbert, J, Wilson, S, Rakic, A and Taimre, T, ‘FPGA implementation of a high-speed, real-time, windowed standard deviation filter’, Electronics Letters, 2016, 52, (1), pp. 22–23). This work is significant because it demonstrates a viable method for the use of optical feedback signals to measure surface roughness without necessitating repeated measurements of the target. It provides evidence for the idea that an online surface roughness sensor could be developed, with the small size and low cost advantages of laser feedback, for use in the manufacturing process of objects with specific roughness tolerances. More broadly, this approach could be applicable to other scenarios in which repeating a measurement is impossible, such as in determining information about a particle randomly passing through the beam. Possible applications of this work in the short term could be in the area of tribology, the measurement of mechanical wear, and in manufacturing processes that require tight control of surface roughness. Longer-term applications are also possible in areas where the measurement quantity of interest can be modelled as the problem of surface roughness, such as in the measurement of particle size. Since this work was completed, further efforts have been directed toward applying the methods in the article to other scenarios in which repeated measurements are not possible. Examples of these situations include the characterisation of uniquely shaped particles passing through the beam, and in the online control of manufacturing processes such as polishing. Optical feedback sensors are unusual in that they are able to measure nanometre-sized changes in optical path length, and yet can be constructed using a small number of compact and relatively inexpensive components. As manufacturers compete to have the most effective quality control and manufacturing processes, sensing techniques such as the one outlined in this article become more and more relevant. Over the coming years, further work in this area could result in low cost sensors that could improve the yield of manufacturing processes through the increased availability of information about process parameters.

This paper reports the demonstration of a widely-translatable fiber-optic mirror based on the motion of liquid metal through the hollow core of a photonic bandgap fiber. By moving a liquid metal mirror within the hollow core of an optical fiber, large, continuous changes in optical path length are achieved in a comparatively small package. A fiber-optic device is demonstrated which provided a continuously-variable optical path length of over 3.6 meters, without the use of free-space optics or resonant optical techniques (i.e. slow light). This change in path length corresponds to a continuously-variable true-time delay of over 12 ns, or 120 periods at a modulation frequency of 10 GHz. Wavelength dependence was shown to be negligible across the C and L bands.

This paper is the second in a set of two investigating tilt-to-length (TTL) coupling. TTL describes the cross-coupling of angular or translational jitter into an interferometric phase signal and is an important noise source in precision interferometers, including space gravitational wave detectors like LISA. We discussed in Hartig et al (2022 J. Opt. 24 065601) the TTL coupling effects originating from optical path length changes, i.e. geometric TTL coupling. Within this work, we focus on the wavefront and detector geometry dependent TTL coupling, called non-geometric TTL coupling, in the case of two interfering fundamental Gaussian beams. We characterise the coupling originating from the properties of the interfering beams, i.e. their absolute and relative angle at the detector, their relative offset and the individual beam parameters. Furthermore, we discuss the dependency of the TTL coupling on the geometry of the detecting photodiode. Wherever possible, we provide analytical expressions for the expected TTL coupling effects. We investigate the non-geometric coupling effects originating from beam walk due to the angular or translational jitter of a mirror or a receiving system. These effects are directly compared with the corresponding detected optical path length changes in Hartig et al (2022 J. Opt. 24 065601). Both together provide the total interferometric readout. We discuss in which cases the geometric and non-geometric TTL effects cancel one-another. Additionally, we list linear TTL contributions that can be used to counteract other TTL effects. Altogether, our results provide key knowledge to minimise the total TTL coupling noise in experiments by design or realignment.

A novel highly sensitive intensity detection method has been proposed based on a self-interference ring resonator, where it is obtained by introducing an additional interference sensing arm between two coupling regions in the conventional planar add-drop micro-ring resonator. By means of dissipative and dispersive coupling mechanisms, optical path length changes of sensing arm not only bring the shift in a resonant wavelength, but also result in the variation of the linewidth and extinction of the spectrum. Using the analytical expression of the transmittance, it is proved that this sensor can monitor optical path length changes of sensing arm with a theoretical detection limit ( $5.6\times 10^{-3}$ nm) by measuring intensity variations at a certain transmission valley.

Detecting cellular activity in sub-millisecond timescale and micrometer resolution without using invasive means has been a long standing goal in the study of cellular networks. Here, we have employed phase sensitive low coherence interferometry for detecting optogenetically stimulated activity of cells. Nanoscale changes in optical path length (due to change in refractive index and changes in cell thickness) occur when cells are activated, which we aim to detect by phase sensitive low coherence interferometry. A low coherence interferometry and patch-clamp electrophysiology systems were integrated with an inverted fluorescence microscope. Blue laser beam was coupled to the electrophysiology-interferometric detection system for optogenetic stimulation. The phase-sensitive measurements were carried out on Channelrhodopsin-2 sensitized cells (identified by YFP fluorescence) as well as control cells in reflection mode for different intensities and exposures of optogenetic stimulation beam. This method offers good temporal and spatial resolution without using exogenous labeling. Results of studies on all optical stimulation and detection of cellular activity will be presented. Interpretation of the optical activity signals will be discussed in context with changes in cell physiology during stimulation. We will also discuss the potential sources of various artifacts in optical/electrical detection of cellular activity during optical stimulation.

We have made attempts to measure directly the small-scale variation of optical path lengths in photopolymer samples. For those with uniform thickness, the measured quantity is supposed to be proportional to the refractive index of the photopolymer. The system is based on a Mach-Zehnder interferometer using phase-locking technique and measures the change in optical path length during the sample is scanned across the optical axis. The spatial resolution is estimated to be 2mm, which is limited by the sample thickness. The path length resolution is estimated to be 6nm, which corresponds to the change in refractive index less than 10 -3 for the sample of 10mm thick. The measurement results showed clearly that the refractive index of photopolymer is not simply proportional to the exposure energy, contrary to the conventional photosensitive materials such as silver halide emulsion and dichromated gelatine. They also revealed the refractive index fluctuation in uniformly exposed photopolymer sample, which explains the milky appearance that sometimes observed in thick samples.

“Experimental Techniques” is an intermediate laboratory course designed in part to help students decide whether they want to pursue experimental physics. Key to this goal are meaningful opportunities for creative exploration and problem solving which mimic real-world research. Despite the COVID-19 pandemic, by building an interferometer at home using inexpensive department-provided materials, students were afforded opportunities for real creativity while proving that changes in optical path length – not just arm length – lead to fringe evolution. Though the physics involved was significantly simpler than in other experiments, students developed a better understanding of optical path length and interferometry while being introduced to instrumentation and some of the fundamental skills used by experimentalists in the lab. Members of the class also gained a meaningful sense of accomplishment and excitement. Consequently, we are now considering implementing this experiment as part of the in-person version of the course.

Direct optical path measurement in fibre-optic gyroscopes: A potential method for compensating slow-drifting errors

Noninvasive functional imaging of molecular and cellular processes of vision may have immense impact on research and clinical diagnostics. Although suitable intrinsic optical signals (IOSs) have been observed ex vivo and in immobilized animals in vivo, detecting IOSs of photoreceptor activity in living humans was cumbersome and time consuming. Here, we observed clear spatially and temporally resolved changes in the optical path length of the photoreceptor outer segment as a response to an optical stimulus in the living human eye. To witness these changes, we evaluated phase data obtained with a parallelized and computationally aberration-corrected optical coherence tomography system. The noninvasive detection of optical path length changes shows neuronal photoreceptor activity of single cones in living human retina, and therefore, it may provide diagnostic options in ophthalmology and neurology and could provide insights into visual phototransduction in humans.

A computer-adapted fiber-optic temperature sensing system has been developed which aims to study both the theoretical aspect of fiber temperature sensing and the experimental aspect of such system. The system consists of a laser source, a fiber sensing element, an electronic fringes counting device, and an on-line personal computer. The temperature measurement is achieved by the conventional double beam fringe counting method with optical path length changes in the sensing beam due to the fiber expansion. The system can automatically measure the temperature changes in a sensing fiber arm which provides an insight of the heat generation and dissipation of the measured system. Unlike the conventional measuring devices such as thermocouples or solid state temperature sensors, the fiber sensor can easily be wrapped and shaped to fit the surface of the measuring object or even inside a molded plastic parts such as a computer case, which gives much more flexibility and applicability to the analysis of heat generation and dissipation in the operation of these machine parts. The reference beam is being set up on a temperature controlled optical bench to facilitate high sensitivity and high temperature resolution. The measuring beam has a motorized beam selection device for multiple fiber beam measurement. The project has been demonstrated in the laboratory and the system sensitivity and resolution are found to be as high as 0.01 degree Celsius. It is expected the system will find its application in many design studies which require thermal budgeting.

Nanometer-scale displacement sensing using self-mixing interferometry with a correlation-based signal processing technique

The optical paths on the LISA bench must have a length instability of less than 10~pm/square root Hz over time scales of 1s to 1000s. A small rigid interferometer has been constructed to measure the optical path length changes using various bonding techniques. The interferometer was constructed entirely from ultra-low expansion (ULE) glass by optically contacting ULE beamsplitters to a ULE bench. Preliminary results taken with the interferometer operating in air indicate optical path length fluctuations of approximately 100 pm/ sqaure root Hz or less for frequencies between 1 mHz and 1 Hz.

The development of lasers, new electro-optic light modulation methods, and improved electronic techniques have made possible significant improvements in the range and accuracy of optical distance measurements, thus providing not only improved ranging methods but also useful techniques for the study of other geo-physical, meteorological, and astronomical problems. One of the main limitations, at present, to the accuracy of distance measurements is the uncertainty in the average propagation velocity of the radiation resulting from inhomogeneity of the atmosphere. Accuracies as high as a few parts in ten million now appear feasible, however, through the use of the dispersion method, in which simultaneous measurements of optical path length at two widely separated wavelengths are used to determine the average refractive index over the path and hence the true geometrical distance. The design of a new instrument based on this method, which utilizes wavelengths of 63281 and 3681X and 3-GHz polarization modulation of the light, is presented. Preliminary measurements over a 5.3-km path with this instrument haXe demonstrated a sensitivity of 3 x 107 in detecting changes in optical path length for either wavelength using 1-sec averageing, and a standard deviation of 3 x 10-7 in corrected length. The principal remaining sources of error are summarized.

This paper proposes a more accurate eccentricity and tilt measurement method based on Young's interference experiment. The basic principle of the method is introduced first before the method is simulated. Then the results are obtained when a to-be-adjusted focusing lens with eccentricity and tilt is simulated. The optical sensitivity also is obtained from these simulation results, and the expression for the change in optical path length caused by eccentricity and tilt is analyzed. Use of this method to detect eccentricity and tilt and assist in adjustment of the system allows the instrument to achieve higher accuracy and thus obtain improved imaging quality and spectral resolution.