Two-photon conversion of a bacterial phytochrome.

In nature, sensory photoreceptors underlie diverse spatiotemporally precise and generally reversible biological responses to light. Photoreceptors also serve as genetically encoded agents in optogenetics to control by light organismal state and behavior. Phytochromes represent a superfamily of photoreceptors that transition between states absorbing red light (Pr) and far-red light (Pfr), thus expanding the spectral range of optogenetics to the near-infrared range. Although light of these colors exhibits superior penetration of soft tissue, the transmission through bone and skull is poor. To overcome this fundamental challenge, we explore the activation of a bacterial phytochrome by a femtosecond laser emitting in the 1 µm wavelength range. Quantum chemical calculations predict that bacterial phytochromes possess substantial two-photon absorption cross sections. In line with this notion, we demonstrate that the photoreversible Pr ↔ Pfr conversion is driven by two-photon absorption at wavelengths between 1170 and 1450 nm. The Pfr yield was highest for wavelengths between 1170 and 1280 nm and rapidly plummeted beyond 1300 nm. By combining two-photon activation with bacterial phytochromes, we lay the foundation for enhanced spatial resolution in optogenetics and unprecedented penetration through bone, skull, and soft tissue.

Pulse dynamics in SESAM-free electrically pumped VECSEL.

Self-starting pulsed operation in an electrically pumped (EP) vertical-external-cavity surface-emitting-laser (VECSEL) without intracavity saturable absorber is demonstrated. A linear hemispherical cavity design, consisting of the EP-VECSEL chip and a 10% output-coupler, is used to obtain picosecond output pulses with energies of 2.8 pJ and pulse widths of 130 ps at a repetition rate of 1.97 GHz. A complete experimental analysis of the generated output pulse train and of the transition from continuous-wave to pulsed operation is presented. Numerical simulations based on a delay-differential-equation (DDE) model of mode-locked semiconductor lasers are used to reproduce the pulse dynamics and identify different laser operation regimes. From this, the measured single pulse operation is attributed to FM-type mode-locking. The pulse formation is explained by strong amplitude-phase coupling and spectral filtering inside the EP-VECSEL.

Femtosecond Alexandrite laser passively mode-locked by an InP/InGaP quantum-dot saturable absorber.

An Alexandrite laser passively mode-locked using an InP/InGaP quantum-dot semiconductor saturable absorber mirror (QD-SESAM) was demonstrated. The laser was pumped at 532 nm and generated pulses as short as 380 fs at 775 nm with an average output power of 295 mW. To the best of our knowledge, this is the first report on a passively mode-locked femtosecond Alexandrite laser using a SESAM in general and a QD-SESAM in particular.

Tunable single- and dual-wavelength SHG from diode-pumped PPKTP waveguides.

A compact, all-room-temperature, widely tunable, continuous wave laser source in the green spectral region (502.1-544.2 nm) with a maximum output power of 14.7 mW is demonstrated. This was made possible by utilizing second-harmonic generation (SHG) in a periodically poled potassium titanyl phosphate (PPKTP) crystal waveguide pumped by a quantum-well external-cavity fiber-coupled diode laser and exploiting the multimode-matching approach in nonlinear crystal waveguides. The dual-wavelength SHG in the wavelength region between 505.4 and 537.7 nm (with a wavelength difference ranging from 1.8 to 32.3 nm) and sum-frequency generation in a PPKTP waveguide is also demonstrated.

Picosecond pulse amplification up to a peak power of 42 W by a quantum-dot tapered optical amplifier and a mode-locked laser emitting at 1.26 µm.

We experimentally study the generation and amplification of stable picosecond-short optical pulses by a master oscillator power-amplifier configuration consisting of a monolithic quantum-dot-based gain-guided tapered laser and amplifier emitting at 1.26 µm without pulse compression, external cavity, gain- or Q-switched operation. We report a peak power of 42 W and a figure-of-merit for second-order nonlinear imaging of 38.5 W2 at a repetition rate of 16 GHz and an associated pulse width of 1.37 ps.

Efficient yellow-green light generation at 561 nm by frequency-doubling of a QD-FBG laser diode in a PPLN waveguide.

A compact high-power yellow-green continuous wave (CW) laser source based on second-harmonic generation (SHG) in a 5% MgO doped periodically poled congruent lithium niobate (PPLN) waveguide crystal pumped by a quantum-dot fiber Bragg grating (QD-FBG) laser diode is demonstrated. A frequency-doubled power of 90.11 mW at the wavelength of 560.68 nm with a conversion efficiency of 52.4% is reported. To the best of our knowledge, this represents the highest output power and conversion efficiency achieved to date in this spectral region from a diode-pumped PPLN waveguide crystal, which could prove extremely valuable for the deployment of such a source in a wide range of biomedical applications.

Self-mode-locked quantum-dot vertical-external-cavity surface-emitting laser.

We present the first self-mode-locked optically pumped quantum-dot semiconductor disk laser. Our mode-locked device emits sub-picosecond pulses at a wavelength of 1040 nm and features a record peak power of 460 W at a repetition rate of 1.5 GHz. In this work, we also investigate the temperature dependence of the pulse duration as well as the time-bandwidth product for stable mode locking.

Wireless Dynamic Light Scattering Sensors Detect Microvascular Changes Associated With Ageing and Diabetes.

This article presents clinical results of wireless portable dynamic light scattering sensors that implement laser Doppler flowmetry signal processing. It has been verified that the technology can detect microvascular changes associated with diabetes and ageing in volunteers. Studies were conducted primarily on wrist skin. Wavelet continuous spectrum calculation was used to analyse the obtained time series of blood perfusion recordings with respect to the main physiological frequency ranges of vasomotions. In patients with type 2 diabetes, the area under the continuous wavelet spectrum in the endothelial, neurogenic, myogenic, and cardio frequency ranges showed significant diagnostic value for the identification of microvascular changes. Aside from spectral analysis, autocorrelation parameters were also calculated for microcirculatory blood flow oscillations. The groups of elderly volunteers and patients with type 2 diabetes, in comparison with the control group of younger healthy volunteers, showed a statistically significant decrease of the normalised autocorrelation function in time scales up to 10 s. A set of identified parameters was used to test machine learning algorithms to classify the studied groups of young controls, elderly controls, and diabetic patients. Our conclusion describes and discusses the classification metrics that were found to be most effective.

P-i-n junction quantum dot saturable absorber mirror: electrical control of ultrafast dynamics.

We report on nonlinear optical properties of a p-i-n junction quantum dot saturable absorber based on InGaAs/GaAs. Absorption recovery dynamics and nonlinear reflectivity are investigated for different reverse bias and pump power conditions. A decrease in absorption recovery time of nearly two orders of magnitude is demonstrated by applying a voltage between 0 and -20 V. The saturable absorber modulation depth and saturation fluence are found to be independent from the applied reverse bias.

Singlet oxygen stimulates mitochondrial bioenergetics in brain cells.

Oxygen, in form of reactive oxygen species (ROS), has been shown to participate in oxidative stress, one of the major triggers for pathology, but also is a main contributor to physiological processes. Recently, it was found that 1267 nm irradiation can produce singlet oxygen without photosensitizers. We used this phenomenon to study the effect of laser-generated singlet oxygen on one of the major oxygen-dependent processes, mitochondrial energy metabolism. We have found that laser-induced generation of 1O2 in neurons and astrocytes led to the increase of mitochondrial membrane potential, activation of NADH- and FADH-dependent respiration, and importantly, increased the rate of maximal respiration in isolated mitochondria. The activation of mitochondrial respiration stimulated production of ATP in these cells. Thus, we found that the singlet oxygen generated by 1267 nm laser pulse works as an activator of mitochondrial respiration and ATP production in the brain.

Conical refraction Nd:KGd(WO4)2 laser.

In 1832 Hamilton predicted conical refraction, concluding that if a beam propagates along an optic axis of a biaxial crystal, a hollow cone of light will emerge. Nearly two centuries on, cascade conical refraction involving multiple crystals has not been investigated. We empirically investigate a unique two-crystal configuration, and use this to demonstrate an ultra-efficient conical refraction Nd:KGd(WO(4))(2) laser providing multi-watt output with excellent beam quality independent of resonator design with a slope efficiency close to the theoretical maximum, offering a new route for power and brightness-scaling in solid-state bulk lasers.

Broadly tunable high-power InAs/GaAs quantum-dot external cavity diode lasers.

A record broadly tunable high-power external cavity InAs/GaAs quantum-dot diode laser with a tuning range of 202 nm (1122 nm-1324 nm) is demonstrated. A maximum output power of 480 mW and a side-mode suppression ratio greater than 45 dB are achieved in the central part of the tuning range. We exploit a number of strategies for enhancing the tuning range of external cavity quantum-dot lasers. Different waveguide designs, laser configurations and operation conditions (pump current and temperature) are investigated for optimization of output power and tunability.

Dual-wavelength mode-locked quantum-dot laser, via ground and excited state transitions: experimental and theoretical investigation.

We report a dual-wavelength passive mode locking regime where picosecond pulses are generated from both ground (lambda = 1263 nm) and excited state transitions (lambda = 1180 nm), in a GaAs-based monolithic two-section quantum-dot laser. Moreover, these results are reproduced by numerical simulations which provide a better insight on the dual-wavelength mode-locked operation.

Optically pumped semiconductor quantum dot disk laser operating at 1180 nm.

We demonstrate an optically pumped semiconductor disk laser using 39 layers of Stranski-Krastanov InGaAs quantum dots self-assembled during epitaxial growth on a monolithic GaAs/AlAs distributed Bragg reflector. The gain structure bonded to an intracavity diamond crystal heat spreader allows 1.75 W single-transverse-mode output (M(2)<1.2) with circular beam shape operating at 1180 nm in a disk laser geometry.

Machine Learning Aided Photonic Diagnostic System for Minimally Invasive Optically Guided Surgery in the Hepatoduodenal Area.

Abdominal cancer is a widely prevalent group of tumours with a high level of mortality if diagnosed at a late stage. Although the cancer death rates have in general declined over the past few decades, the mortality from tumours in the hepatoduodenal area has significantly increased in recent years. The broader use of minimal access surgery (MAS) for diagnostics and treatment can significantly improve the survival rate and quality of life of patients after surgery. This work aims to develop and characterise an appropriate technical implementation for tissue endogenous fluorescence (TEF) and assess the efficiency of machine learning methods for the real-time diagnosis of tumours in the hepatoduodenal area. In this paper, we present the results of the machine learning approach applied to the optically guided MAS. We have elaborated tissue fluorescence approach with a fibre-optic probe to record the TEF and blood perfusion parameters during MAS in patients with cancers in the hepatoduodenal area. The measurements from the laser Doppler flowmetry (LDF) channel were used as a sensor of the tissue vitality to reduce variability in TEF data. Also, we evaluated how the blood perfusion oscillations are changed in the tumour tissue. The evaluated amplitudes of the cardiac (0.6-1.6 Hz) and respiratory (0.2-0.6 Hz) oscillations was significantly higher in intact tissues (p < 0.001) compared to the cancerous ones, while the myogenic (0.2-0.06 Hz) oscillation did not demonstrate any statistically significant difference. Our results demonstrate that a fibre-optic TEF probe accompanied with ML algorithms such as k-Nearest Neighbours or AdaBoost is highly promising for the real-time in situ differentiation between cancerous and healthy tissues by detecting the information about the tissue type that is encoded in the fluorescence spectrum. Also, we show that the detection can be supplemented and enhanced by parallel collection and classification of blood perfusion oscillations.

Multimodal Optical Diagnostics of the Microhaemodynamics in Upper and Lower Limbs.

The introduction of optical non-invasive diagnostic methods into clinical practice can substantially advance in the detection of early microcirculatory disorders in patients with different diseases. This paper is devoted to the development and application of the optical non-invasive diagnostic approach for the detection and evaluation of the severity of microcirculatory and metabolic disorders in rheumatic diseases and diabetes mellitus. The proposed methods include the joint use of laser Doppler flowmetry, absorption spectroscopy and fluorescence spectroscopy in combination with functional tests. This technique showed the high diagnostic importance for the detection of disturbances in peripheral microhaemodynamics. These methods have been successfully tested as additional diagnostic techniques in the field of rheumatology and endocrinology. The sensitivity and specificity of the proposed diagnostic procedures have been evaluated.

Boosting Terahertz Photoconductive Antenna Performance with Optimised Plasmonic Nanostructures.

Advanced nanophotonics penetrates into other areas of science and technology, ranging from applied physics to biology, which results in many fascinating cross-disciplinary applications. It has been recently demonstrated that suitably engineered light-matter interactions at the nanoscale can overcome the limitations of today's terahertz (THz) photoconductive antennas, making them one step closer to many practical implications. Here, we push forward this concept by comprehensive numerical optimization and experimental investigation of a log-periodic THz photoconductive antenna coupled to a silver nanoantenna array. We shed light on the operation principles of the resulting hybrid THz antenna, providing an approach to boost its performance. By tailoring the size of silver nanoantennas and their arrangement, we obtain an enhancement of optical-to-THz conversion efficiency 2-fold larger compared with previously reported results for similar structures, and the strongest enhancement is around 1 THz, a frequency range barely achievable by other compact THz sources. We also propose a cost-effective fabrication procedure to realize such hybrid THz antennas with optimized plasmonic nanostructures via thermal dewetting process, which does not require any post processing and makes the proposed solution very attractive for applications.

3D laser nano-printing on fibre paves the way for super-focusing of multimode laser radiation.

Multimode high-power laser diodes suffer from inefficient beam focusing, leading to a focal spot 10-100 times greater than the diffraction limit. This inevitably restricts their wider use in 'direct-diode' applications in materials processing and biomedical photonics. We report here a 'super-focusing' characteristic for laser diodes, where the exploitation of self-interference of modes enables a significant reduction of the focal spot size. This is achieved by employing a conical microlens fabricated on the tip of a multimode optical fibre using 3D laser nano-printing (also known as multi-photon lithography). When refracted by the conical surface, the modes of the fibre-coupled laser beam self-interfere and form an elongated narrow focus, usually referred to as a 'needle' beam. The multiphoton lithography technique allows the realisation of almost any optical element on a fibre tip, thus providing the most suitable interface for free-space applications of multimode fibre-delivered laser beams. In addition, we demonstrate the optical trapping of microscopic objects with a super-focused multimode laser diode beam thus rising new opportunities within the applications sector where lab-on-chip configurations can be exploited. Most importantly, the demonstrated super-focusing approach opens up new avenues for the 'direct-diode' applications in material processing and 3D printing, where both high power and tight focusing is required.

Multimodal optical measurement for study of lower limb tissue viability in patients with diabetes mellitus.

According to the International Diabetes Federation, the challenge of early stage diagnosis and treatment effectiveness monitoring in diabetes is currently one of the highest priorities in modern healthcare. The potential of combined measurements of skin fluorescence and blood perfusion by the laser Doppler flowmetry method in diagnostics of low limb diabetes complications was evaluated. Using Monte Carlo probabilistic modeling, the diagnostic volume and depth of the diagnosis were evaluated. The experimental study involved 76 patients with type 2 diabetes mellitus. These patients were divided into two groups depending on the degree of complications. The control group consisted of 48 healthy volunteers. The local thermal stimulation was selected as a stimulus on the blood microcirculation system. The experimental studies have shown that diabetic patients have elevated values of normalized fluorescence amplitudes, as well as a lower perfusion response to local heating. In the group of people with diabetes with trophic ulcers, these parameters also significantly differ from the control and diabetes only groups. Thus, the intensity of skin fluorescence and level of tissue blood perfusion can act as markers for various degrees of complications from the beginning of diabetes to the formation of trophic ulcers.

Computational model of bladder tissue based on its measured optical properties.

Urinary bladder diseases are a common problem throughout the world and often difficult to accurately diagnose. Furthermore, they pose a heavy financial burden on health services. Urinary bladder tissue from male pigs was spectrophotometrically measured and the resulting data used to calculate the absorption, transmission, and reflectance parameters, along with the derived coefficients of scattering and absorption. These were employed to create a "generic" computational bladder model based on optical properties, simulating the propagation of photons through the tissue at different wavelengths. Using the Monte-Carlo method and fluorescence spectra of UV and blue excited wavelength, diagnostically important biomarkers were modeled. Additionally, the multifunctional noninvasive diagnostics system "LAKK-M" was used to gather fluorescence data to further provide essential comparisons. The ultimate goal of the study was to successfully simulate the effects of varying excited radiation wavelengths on bladder tissue to determine the effectiveness of photonics diagnostic devices. With increased accuracy, this model could be used to reliably aid in differentiating healthy and pathological tissues within the bladder and potentially other hollow organs.