This article is a reflection on the themes of the Faraday Discussion meeting on "Biological and bio-inspired optics" held from 20 to 22 July 2020. It is a personal perspective on the nature of this field as a broad and interdisciplinary field that has led to a sound understanding of the material properties of biological nanostructured and optical materials. The article describes how the nature of the field and the themes of the conference are reflected in particular in work on the 3D bicontinuous biophotonic nanostructures known as single gyroids and in bicontinuous structures more broadly. Such single gyroid materials are found for example in the butterfly Thecla opisena, where the questions of biophotonic response, of bio-inspired optics, of the relationship between structure and function, and of the relationship between natural and synthetic realisations are closely interlinked. This multitude of facets of research on single gyroid structures reflects the beauty of the broader field of biophotonics, namely as a field that lives through embracing the serendipitous discovery of the biophotonic marvels that nature offers to us as seeds for in-depth analysis and understanding. The m
Broad and safe access to ultrafast laser technology has been hindered by the absence of optical fiber-delivered pulses with tunable central wavelength, pulse repetition rate, and pulse width in the picosecond-femtosecond regime. To address this long-standing obstacle, we developed a reliable accessory for femtosecond ytterbium fiber chirped pulse amplifiers, termed as fiber-optic nonlinear wavelength converter (FNWC), as an adaptive optical source for the emergent field of femtosecond biophotonics. This accessory embowers the fixed-wavelength laser to produce fiber delivered ~20 nJ pulses with central wavelength across 950-1150 nm, repetition rate across 1-10 MHz, and pulse width across 40-400 fs, with a long-term stability of >2000 hrs. As a prototypical label-free application in biology and medicine, we demonstrate the utility of FNWC in real-time intravital imaging synergistically integrated with modern machine learning and large-scale fluorescence lifetime imaging microscopy.
Biophotonic techniques are growing in rapid rhythms enabling the monitoring of subcellular structures and non-invasive theranostic interventions in cancer and autoimmune diseases. The integration of Biophotonics with nanotechnology and biosensors brings a revolution in the micro- and nano-world with new optical tools. Among them, optical tweezers revive as a potential tool for tracking cells behavior and probing interactions forces between cells, cells-biomolecules and cells-nanoparticles. In this review we aim to exhibit the state-of the art advances of the Biophotonics in the diagnostic and therapeutic field, and the role of optical tweezers.
Single-photon avalanche diode (SPAD) arrays are solid-state detectors offering imaging capabilities at the level of individual photons, with unparalleled photon counting and time-resolved performance. This fascinating technology has progressed at very high pace in the past 15~years, since its inception in standard CMOS technology in 2003. A host of architectures has been explored, ranging from simpler implementations, based solely on off-chip data processing, to progressively ``smarter" sensors including on-chip, or even pixel-level, timestamping and processing capabilities. As the technology matured, a range of biophotonics applications has been explored, including (endoscopic) FLIM, (multi-beam multiphoton) FLIM-FRET, SPIM-FCS, super-resolution microscopy, time-resolved Raman, NIROT, and PET. We will review some representative sensors and their corresponding applications, including the most relevant challenges faced by chip designers and end-users. Finally, we will provide an outlook on the future of this fascinating technology.
We discuss efficient algorithms for the accurate forward and reverse evaluation of the discrete Fourier-Bessel transform (dFBT) as numerical tools to assist in the 2D polar convolution of two radially symmetric functions, relevant, e.g., to applications in computational biophotonics. In our survey of the numerical procedure we account for the circumstance that the objective function might result from a more complex measurement process and is, in the worst case, known on a finite sequence of coordinate values, only. We contrast the performance of the resulting algorithms with a procedure based on a straight forward numerical quadrature of the underlying integral transform and asses its efficienty for two benchmark Fourier-Bessel pairs. An application to the problem of finite-size beam-shape convolution in polar coordinates, relevant in the context of tissue optics and optoacoustics, is used to illustrate the versatility and computational efficiency of the numerical procedure.
To illustrate the power of the biophysical approach in solving important problems in life science, I present here one of our current research projects as an example. We have developed special biophotonic techniques to study the dynamic properties of signaling proteins in a single living cell. Such a study allowed us to gain new insight into the signaling mechanism that regulates programmed cell death.
Droplet microlasers, as promising tools for biophotonics and biomedical sciences, have witnessed rapid advances due to their flexible reconfigurability, high sensitivity to stimuli, and label-free biosensing ability. However, designing these biosensors with simultaneously critical properties of low lasing threshold, high spectral purity, and ultimate sensitivity remains challenging. Here, we propose a versatile strategy to build liquid photonic molecules (LPMs) that combine all these features in a single device. We find that through tailoring the spectral Vernier overlap in size-mismatched droplets, this device enables single-mode lasing with a low threshold of ~610 nJ mm-2. The LPM lasers are engineered for dynamic tunability using a molecular isomerization strategy, which induces spectral mode hopping and thus yields a nearly ten-fold enhancement in spectral sensitivity over single droplets. Moreover, by leveraging the self-referenced intensity response of the LPM lasing modes, we demonstrate a three-orders-of-magnitude enhancement in biomolecular sensing, with a detection limit of 30 aM and a dynamic range spanning nine orders of magnitude. Our work offers exciting prospects for
Optical forces - studied since the earliest days of laser physics - continue to reveal rich dynamics and enable powerful tools for manipulation of objects on micro- and nanoscales, and even individual atoms. Lateral optical forces, which act perpendicular to the direction of beam propagation, are particularly intriguing but have largely been restricted to interface geometries such as air - water boundaries. Here, we realize tunable lateral optical force entirely within a fluid environment by using Janus particles: dielectric microspheres half-coated with gold. We show that the lateral optical force arises from scattering asymmetry induced by the asymmetric structure of the particles; it can be tuned by adjusting the polarization angle of a linearly polarized beam, but also particle parameters including their size and orientation. Experimentally, we directly observe fully reversible lateral propulsion of Janus particles in water merely by rotating the polarization direction, in excellent agreement with theoretical predictions. These results establish a new mechanism for programmable, polarization-controlled optical manipulation, with promising implications for biophotonics, microflu
Biophotons are ultra-weak photon emissions in the visible spectrum produced by living organisms. While extensively studied in plants, germinating seeds, and cell cultures, no systematic multi-method complexity analysis of human ultraweak photon emission (UPE) under physiological modulation has been reported. We address this gap by applying a comprehensive analytical framework to UPE measurements from the right palm of a human subject. Three independent sessions were conducted on different days, each comprising four consecutive 15-minute phases: Dark reference, pre-meditation resting state (Pre), structured meditation based on the Sama Vritti box-breathing protocol, and post-meditation recovery (Post). Photon count series are analysed with four complementary methods: distributional statistics (Fano factor, skewness, tail Expected Shortfall); multiscale Fano factor and Allan deviation; stripe-filtered Diffusion Entropy Analysis (DEA); and Renyi entropy with a Time Reversal test. The methods show complementary sensitivities, converging on a coherent picture: a systematic reduction of emission intermittency during meditation, consistently detected across all three sessions. Stripe-filt
Ultraweak photon emission, also referred to as biological autoluminescence or biophoton emission, is the spontaneous emission of extremely low levels of light from a broad range of biological systems. Recent studies have reported that UPE measured extracranially can serve as a potential non-invasive biomarker of brain activity. Here, we show that this interpretation suffers from serious problems. We show that, when observed under properly dark conditions, the UPE from the head is much weaker than what is reported in certain papers on 'brain UPE' from human heads. We also show that the large signals reported in these studies can be explained by background light contamination. Furthermore, photons with wavelengths < 600 nm are strongly attenuated by scalp and skull tissues, and longer wavelengths fall largely outside the effective spectral sensitivity of the photomultiplier tubes (PMTs) used. As a consequence, even if UPE from the head is detected under properly background-free conditions, it is likely to be dominated by emission from the scalp rather than from the brain, certainly as long as PMTs are used. Our results emphasize the importance of careful experimental design to mak
Biophotonic signaling via axons has been proposed as a potential mode of neural communication, where information might be encoded not only in photon number and wavelength but also in polarization. Although earlier computational studies have examined how structural imperfections influence optical transmission, their effects on polarization fidelity remain unexplored; previous modeling of polarization fidelity in myelinated axons has largely focused on idealized geometries. This study incorporates three structural imperfections characteristic of axons in vivo: variation in myelin thickness, non-circular cross-sectional geometry, and axonal bending, within a model that includes four nodes of Ranvier. We find that variation in myelin thickness alone has minimal impact on fidelity, while non-circular cross-sections show strong mode dependence. Axonal bending has the most significant influence, generating large fluctuations and deep fidelity dips. When all imperfections are combined in a single axon model, the simulations show substantial drops in fidelity, yet certain modes exhibit recovery, with repeated revivals reaching values of around 0.8, which exceeds the revivals observed in the
Understanding the nuances of nonlinear pulse propagation in optical fibers has led to several impactful applications across domains like optical communications, sensing and biophotonics. A key aspect in this regard is the use of appropriate optimization strategies for attaining requisite performance parameters. In this paper, we present the Taguchi method as a viable tool for optimizing nonlinear pulse propagation in optical fibers. We show that its use of the orthogonal arrays leads to rapid convergences to the desired pulse parameters, with even faster convergences obtained by favouring exploitation over exploration. We demonstrate the application of the method using two well-known problems from the field - the guiding center soliton, and soliton order conservation in dispersion decreasing fibers - which serve to underscore its salient features and also its potential for solution discovery across nonlinear pulse propagation problems.
Advances in silicon (Si) photonics at submicrometer wavelengths are unlocking new opportunities to realize miniaturized, scalable optical systems for biophotonics, quantum information, imaging, spectroscopy, and displays. Addressing this array of applications with a single integrated photonics technology requires the development of high-performance active components compatible with both visible and near-infrared light. Here, we report waveguide-coupled photodetectors monolithically integrated in a foundry-fabricated, short-wavelength, Si photonics platform. We demonstrate two detector variants that collectively cover a continuous wavelength span of $λ=$ 400 - 955 nm. The devices exhibited external quantum efficiencies exceeding 60% and 12% over 400 - 748 nm and 749 - 955 nm wavelength ranges, respectively. Measured dark currents were $<$ 2 pA at a 2 V reverse bias. High-speed measurements at $λ=$ 785 nm demonstrated optoelectronic bandwidths up to 18 GHz. Avalanche operation was characterized, yielding a gain-bandwidth product of 374 GHz.
The photophysical properties of deoxyribonucleic acid (DNA) are fundamental to life sciences and biophotonics. While previous studies have generally been restricted to fluorescence, attributing it to pi-pi* transitions and charge transfer within nucleobases in dilute solution, these understandings fail to explain the pronounced visible emission in physiological and aggregated states, and moreover, ignore the possible phosphorescence. Addressing this critical gap, we systematically investigate native DNA across its structural hierarchy, from nucleobases to single-stranded chains, under varying states. We demonstrate that DNA exhibits excitation-dependent emission in aggregates and moreover room-temperature phosphorescence (RTP) in the solid state. These behaviors are rationalized by the clustering-triggered emission (CTE) mechanism, where nucleobases and electron-rich nonaromatic moieties like sugar and phosphate synergistically contribute to DNA photophysics. High-pressure experiments reveal a 207-fold luminescence enhancement for nucleotides at 26 GPa, largely retained after decompression, underscoring the precise control of emission by intermolecular interactions. This study not
Biophotons are non-thermal and non-bioluminescent ultraweak photon emissions, first hypothesised by Gurwitsch in 1924 as a regulatory mechanism in cell division, and then experimentally observed in living organisms. Today, two main hypotheses explain their origin: stochastic decay of excited molecules and coherent electromagnetic fields produced in biochemical processes. Recent interest focuses on the role of biophotons in cellular communication and disease monitoring. This study presents the first campaign of biophoton emission measurements from cultured astrocytes and glioblastoma cells, conducted at Fondazione Pisana per la Scienza (FPS) using two ultra-sensitive setups developed by the collaboration at the National Laboratories of Frascati (LNF-INFN) and at the University of Rome II - Tor Vergata. The statistical analyses of the data collected revealed a clear separation between cellular signals and dark noise, confirming the high sensitivity of the apparatuses. The Diffusion Entropy Analysis (DEA) was applied to the data to uncover dynamic patterns, revealing anomalous diffusion and long-range memory effects potentially related to intercellular signalling and cellular communic
Point spread function (PSF) engineering is vital for precisely controlling the focus of light in computational imaging, with applications in neural imaging, fluorescence microscopy, and biophotonics. The PSF is derived from the magnitude of the Fourier transform of a phase function, making the construction of the phase function given the PSF (PSF engineering) an ill-posed inverse problem. Traditional PSF engineering methods rely on physical basis functions, limiting their ability to generalize across the range of PSFs required for imaging tasks. We introduce a novel approach leveraging implicit neural representations that overcome the limitations of pixel-wise optimization methods. Our approach achieves a median MSSIM of 0.8162 and a mean MSSIM of 0.5634, compared to a median MSSIM of 0.0 and a mean MSSIM of 0.1841 with pixel-wise optimization when learning randomly generated phase functions. Our approach also achieves a median PSNR of 10.38 dB and a mean PSNR of 8.672 dB, compared to a median PSNR of 6.653 dB and a mean PSNR of 6.660 dB with pixel-wise optimization for this task.
Optical modulators in the visible regime have far-reaching applications from biophotonics to quantum science. Implementations of such optical phase modulators on a complementary metal-oxide-semiconductor (CMOS) compatible platform have been mainly limited to utilization of the thermo-optic effect, liquid crystal technology, as well as piezo-optomechanical effects. Despite excellent performance, the demonstrations using the thermo-optic effect and liquid crystal technology both suffer from limited modulation speed. Moreover, the demonstrations utilizing piezo-optomechanical effects, require very large footprints due to a weak modulation efficiency. Here, we report the demonstration of the first highly scalable compact CMOS-compatible phase modulator in the visible regime based on altering the refractive index of an indium-tin oxide capacitive stack over a Si${_3}$N${_4}$ waveguide through the charge accumulation effect. The implemented modulator achieves a two orders-of-magnitude larger bandwidth compared to thermo-optic and liquid crystal based counterparts and close to 3 orders-of-magnitude higher modulation efficiency with about two orders-of-magnitude smaller footprint compared
Key pre-synaptic and post-synaptic biological functions have been successfully implemented in various hardware systems. A noticeable example are neuronal networks constructed from memristors, which are emulating complex electro-chemical biological dynamics such a neuron's efficacy and plasticity. Neurons are highly active cells, communicating with chemical and electrical stimuli, but also emit light. These photons are suspected to be a complementary vehicle to transport information across the brain. Here, we show that a memristor also releases photons akin to the production of neuronal light. Critical attributes of so-called biophotons such as self-generation, origin, stochasticity, spectral coverage, sparsity and correlation with the neuron's activity are replicated by our solid-state approach. Our findings further extend the emulating capability of a memristor to encompass neuronal biophoton emission and open the possibility to construct a bimodal electro-optical platform with the assistance of atomic-scale devices capable of handling electrons and photons as information carriers.
Thin film interference is integral to modern photonics and optoelectronics, e.g. allowing for precise design of high performance optical filters, efficiency enhancements in photovoltaics and light-emitting devices, as well as the realization of microlasers and high-performance photodetectors. However, interference inevitably leads to a change of spectral characteristics with angle, which is generally undesired and can limit the usefulness of thin-film coatings and devices. Here, we introduce a strategy to overcome this fundamental limit in optics by utilizing and tuning the exciton-polariton modes arising in ultra-strongly coupled microcavities. We demonstrate optical filters with narrow pass bands that shift by less than their half width (<15 nm) even at extreme angles. Our filters cover the entire visible range and surpass comparable metal-dielectric-metal filters in all relevant metrics. By expanding this strategy to strong coupling with the photonic sidebands of dielectric multilayer stacks, we also obtain filters with high extinction ratios and up to 98% peak transmission. Based on these findings, we realize ultrathin and flexible narrowband filter films, monolithically int
About a hundred years ago the Russian biologist A. Gurwitsch, based on his experiments with onion plants by measuring their growth rate, made the hypothesis that plants emitted a weak electromagnetic field which somehow influenced cell growth. This interesting observation remained fundamentally ignored by the scientific community and only in the 1950s the electromagnetic emission from some plants was measured using a photomultiplier used in single counting mode. Later, in the 80s several groups in the world started some extensive work to understand the origin and role of this ultra-weak emission, hereby called biophotons, coming from living organisms. Biophotons are an endogenous very small production of photons in the visible energy range in and from cells and organism, and this emission is characteristic of alive organisms. Today there is no doubt that biophotons really exist, this emission has in fact been measured by many groups and on many different living organisms, from humans to bacteria. On the contrary, the origin of biophotons and whether organisms use them in some way to exchange information is not yet well known; no model proposed since now is really capable of reprodu