Controlling and scripting laboratory hardware with open-source, intuitive interfaces: OpenFlexure Voice Control and OpenFlexure Blockly.

Making user interaction with laboratory equipment more convenient and intuitive should promote experimental work and help researchers to complete their tasks efficiently. The most common form of interaction in current instrumentation is either direct tactile, with buttons and knobs, or interfaced through a computer, using a mouse and keyboard. Scripting is another function typical of smart and automated laboratory equipment, yet users are currently required to learn bespoke programming languages and libraries for individual pieces of equipment. In this paper, we present two open-source, novel and intuitive ways of interacting with and scripting laboratory equipment. We choose the OpenFlexure family of microscopes as our exemplar, due to their open-source nature and smart control system. Firstly, we demonstrate 'OpenFlexure Voice Control' to enable users to control the microscope hands-free. Secondly, we present 'OpenFlexure Blockly' which uses the Blockly Visual Programming Language to enable users to easily create scripts for the microscope, using a drag and drop Web interface. We explain the design choices when developing these tools, and discuss more typical use cases and more general applications.

Multi-modal microscopy imaging with the OpenFlexure Delta Stage.

Microscopes are vital pieces of equipment in much of biological research and medical diagnostics. However, access to a microscope can represent a bottleneck in research, especially in lower-income countries. 'Smart' computer controlled motorized microscopes, which can perform automated routines or acquire images in a range of modalities are even more expensive and inaccessible. Developing low-cost, open-source, smart microscopes enables more researchers to conceive and execute optimized or more complex experiments. Here we present the OpenFlexure Delta Stage, a 3D-printed microscope designed for researchers. Powered by the OpenFlexure software stack, it is capable of performing automated experiments. The design files and assembly instructions are freely available under an open licence. Its intuitive and modular design-along with detailed documentation-allows researchers to implement a variety of imaging modes with ease. The versatility of this microscope is demonstrated by imaging biological and non-biological samples (red blood cells with Plasmodium parasites and colloidal particles in brightfield, epi-fluorescence, darkfield, Rheinberg and differential phase contrast. We present the design strategy and choice of tools to develop devices accessible to researchers from lower-income countries, as well as the advantages of an open-source project in this context. This microscope, having been open-source since its conception, has already been built and tested by researchers around the world, promoting a community of expertise and an environment of reproducibility in science.

autohaem: 3D printed devices for automated preparation of blood smears.

The process of making blood smears is common in both research and clinical settings for investigating the health of blood cells and the presence of blood-borne parasites. It is very often carried out manually. We focus here on smears for malaria diagnosis and research, which are frequently analyzed by optical microscopy and require a high quality. Automating the smear preparation promises to increase throughput and to improve the quality and consistency of the smears. We present here two devices (manual and motorized) designed to aid in the making of blood smears. These are fully documented, open-source hardware, and an important principle was to make them easily fabricated locally anywhere. Designs and assembly instructions are freely available under an open license. We also describe an image analysis pipeline for characterizing the quality of smears and use it to optimize the settings and tunable parameters in the two devices. The devices perform as well as expert human operators while not requiring a trained operator and offering potential advantages in reproducibility and standardization across facilities.

Fast, high-precision autofocus on a motorised microscope: Automating blood sample imaging on the OpenFlexure Microscope.

The OpenFlexure Microscope is a 3D-printed, low-cost microscope capable of automated image acquisition through the use of a motorised translation stage and a Raspberry Pi imaging system. This automation has applications in research and healthcare, including in supporting the diagnosis of malaria in low-resource settings. The plasmodium parasites that cause malaria require high magnification imaging, which has a shallow depth of field, necessitating the development of an accurate and precise autofocus procedure. We present methods of identifying the focal plane of the microscope, and procedures for reliably acquiring a stack of focused images on a system affected by backlash and drift. We also present and assess a method to verify the success of autofocus during the scan. The speed, reliability and precision of each method are evaluated, and the limitations discussed in terms of the end users' requirements.

Simplifying the OpenFlexure microscope software with the web of things.

We present the OpenFlexure Microscope software stack which provides computer control of our open source motorised microscope. Our diverse community of users needs both graphical and script-based interfaces. We split the control code into client and server applications interfaced via a web API conforming to the W3C Web of Things standard. A graphical interface is viewed either in a web browser or in our cross-platform Electron application, and gives basic interactive control including common operations such as Z stack acquisition and tiled scanning. Automated control is possible from Python and Matlab, or any language that supports HTTP requests. Network control makes the software stack more robust, allows multiple microscopes to be controlled by one computer, and facilitates sharing of equipment. Graphical and script-based clients can run simultaneously, making it easier to monitor ongoing experiments. We have included an extension mechanism to add functionality, for example controlling additional hardware components or adding automation routines. Using a Web of Things approach has resulted in a user-friendly and extremely versatile software control solution for the OpenFlexure Microscope, and we believe this approach could be generalized in the future to make automated experiments involving several instruments much easier to implement.

Testing the Sensitivity of the Galactic Center Excess to the Point Source Mask.

The Fermi Large Area Telescope (Fermi-LAT) Collaboration has an updated point source catalog, referred to as 4FGL. We perform the first template fit using a mask based on this new catalog and find that the excess in gamma rays detected at the Galactic Center in Fermi-LAT data persists. On the other hand, we find that a search for point sources is highly sensitive to the use of the 4FGL catalog: no sizable excess of bright pixels is apparent in the inner Galaxy when we mask out 4FGL point sources. Combining these observations restricts the ability of point sources to contribute to the Galactic Center excess. After identifying which bright sources have no known counterpart, we place strong constraints on any point source luminosity function capable of explaining the smooth emission identified in the template fit.

Robotic microscopy for everyone: the OpenFlexure microscope.

Optical microscopes are an essential tool for both the detection of disease in clinics, and for scientific analysis. However, in much of the world access to high-performance microscopy is limited by both the upfront cost and maintenance cost of the equipment. Here we present an open-source, 3D-printed, and fully-automated laboratory microscope, with motorised sample positioning and focus control. The microscope is highly customisable, with a number of options readily available including trans- and epi- illumination, polarisation contrast imaging, and epi-florescence imaging. The OpenFlexure microscope has been designed to enable low-volume manufacturing and maintenance by local personnel, vastly increasing accessibility. We have produced over 100 microscopes in Tanzania and Kenya for educational, scientific, and clinical applications, demonstrating that local manufacturing can be a viable alternative to international supply chains that can often be costly, slow, and unreliable.

Beyond the Standard Model Explanations of GW190521.

The LIGO-Virgo Collaboration has recently announced the detection of a heavy binary black hole merger, with component masses that are difficult to account for in standard stellar structure theory. In this Letter, we propose several explanations based on models of new physics, including new light particle losses, modified gravity, large extra dimensions, and a small magnetic moment of the neutrino. Each of these affect the physics of the pair instability differently, leading to novel mechanisms for forming black holes inside the mass gap.

Constraining the Self-Interacting Neutrino Interpretation of the Hubble Tension.

Large, nonstandard neutrino self-interactions have been shown to resolve the ∼4σ tension in Hubble constant measurements and a milder tension in the amplitude of matter fluctuations. We demonstrate that interactions of the necessary size imply the existence of a force carrier with a large neutrino coupling (>10^{-4}) and mass in the keV-100 MeV range. This mediator is subject to stringent cosmological and laboratory bounds, and we find that nearly all realizations of such a particle are excluded by existing data unless it carries spin 0 and couples almost exclusively to τ-flavored neutrinos. Furthermore, we find that the light neutrinos must be Majorana particles, and that a UV-complete model requires a nonminimal mechanism to simultaneously generate neutrino masses and appreciable self-interactions.

Constraining Dissipative Dark Matter Self-Interactions.

We study the gravothermal evolution of dark matter halos in the presence of dissipative dark matter self-interactions. Dissipative interactions are present in many particle-physics realizations of the dark-sector paradigm and can significantly accelerate the gravothermal collapse of halos compared to purely elastic dark matter self-interactions. This is the case even when the dissipative interaction timescale is longer than the free-fall time of the halo. Using a semianalytical fluid model calibrated with isolated and cosmological N-body simulations, we calculate the evolution of the halo properties-including its density profile and velocity dispersion profile-as well as the core-collapse time as a function of the particle model parameters that describe the interactions. A key property is that the inner density profile at late times becomes cuspy again. Using 18 dwarf galaxies that exhibit a corelike dark matter density profile, we derive constraints on the strength of the dissipative interactions and the energy loss per collision.

Can the Inflaton Also Be a Weakly Interacting Massive Particle?

We propose a class of models in which a stable inflaton is produced as a thermal relic in the early Universe and constitutes the dark matter. We show that inflaton annihilations can efficiently reheat the Universe, and identify several examples of inflationary potentials that can accommodate all cosmic microwave background observables and in which the inflaton dark matter candidate has a weak scale mass. As a simple example, we consider annihilations that take place through a Higgs portal interaction, leading to encouraging prospects for future direct detection experiments.

Near-field ptychographic microscope for quantitative phase imaging.

Quantitative phase imaging (QPI) is the name given to a set of microscopy techniques that map out variations in optical path lengths across a sample. These maps are a useful source of contrast for transparent samples such as biological cells, and because they are quantitative they can be used to measure refractive index and thickness variations. Here we detail the setup and operation of a new form of QPI microscope based on near-field ptychography. We test our system using a range of phase objects, and analyse the phase images it produces. Our results show that accurate, high quality images can be obtained from a ptychographical dataset containing as few as four near-field diffraction patterns. We also assess how our system copes with optically thick samples and samples with a wide range of spatial frequencies - two areas where conventional and Fourier ptychography struggle.

Severely Constraining Dark-Matter Interpretations of the 21-cm Anomaly.

The EDGES Collaboration has recently reported the detection of a stronger-than-expected absorption feature in the global 21-cm spectrum, centered at a frequency corresponding to a redshift of z≃17. This observation has been interpreted as evidence that the gas was cooled during this era as a result of scattering with dark matter. In this Letter, we explore this possibility, applying constraints from the cosmic microwave background, light element abundances, Supernova 1987A, and a variety of laboratory experiments. After taking these constraints into account, we find that the vast majority of the parameter space capable of generating the observed 21-cm signal is ruled out. The only viable models are those in which a small fraction, ∼0.3%-2%, of the dark matter consists of particles with a mass of ∼10-80 MeV and which couple to the photon through a small electric charge, roughly 10^{-6}-10^{-4} as large as the electron charge. Furthermore, in order to avoid being overproduced in the early Universe, such models must be supplemented with an additional depletion mechanism, such as annihilations through a L_{µ}-L_{τ} gauge boson or annihilations to a pair of rapidly decaying hidden sector scalars.

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

We suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v^{n}∼(10^{-(2-3)})^{n}, where n=1, 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ∼0.1-1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ∼O(100 MeV). Dark fusion firmly predicts constant σv below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.

Characterizing a spatial light modulator using ptychography.

Ptychography is used to characterize the phase response of a spatial light modulator (SLM). We use the technique to measure and correct the optical curvature and the gamma curve of the device. Ptychography's unique ability to extend field of view is then employed to test performance by mapping the phase profile generated by a test image to subpixel resolution over the entire active region of the SLM.

Inflatable Dark Matter.

We describe a general scenario, dubbed "inflatable dark matter," in which the density of dark matter particles can be reduced through a short period of late-time inflation in the early Universe. The overproduction of dark matter that is predicted within many, otherwise, well-motivated models of new physics can be elegantly remedied within this context. Thermal relics that would, otherwise, be disfavored can easily be accommodated within this class of scenarios, including dark matter candidates that are very heavy or very light. Furthermore, the nonthermal abundance of grand unified theory or Planck scale axions can be brought to acceptable levels without invoking anthropic tuning of initial conditions. A period of late-time inflation could have occurred over a wide range of scales from ∼MeV to the weak scale or above, and could have been triggered by physics within a hidden sector, with small but not necessarily negligible couplings to the standard model.