Stratum corneum (SC) biomarkers such as its thickness and hydration level offer valuable information about the state of the skin barrier. A Fourier domain visible light optical coherence tomography (VIS-OCT) system with an axial resolution of ~1 μm in tissue, was used to assess the morphology of the human SC layer under different hydration conditions. 12 human subjects (7 males, 5 females) in an age group of 21-59 were recruited. B-scan images of subjects’ dorsal hands were recorded by the VIS-OCT system and processed in MATLAB and GraphPad. An average SC thickness in the dorsal area before hydration, after hydration in water for 40 minutes and after drying in air for 40 minutes were found to be: 9 μm ± 0.1 μm, 19 μm ± 0.2 μm and 8 μm ± 0.1 μm, correspondingly. SC reflectance, obtained by VIS-OCT, changes at different hydration levels, increasing in a range of |4-12|dB during the hydration phase and decreasing in a range of |4-13|dB during the dehydration phase. That SC reflectance data correlates moderately to strongly, depending on an individual, with SC hydration levels measured by a Corneometer.
Atopic dermatitis, or eczema, is a widespread chronic skin condition mainly treated with steroid creams, which can cause side effects such as skin thinning. Optical coherence tomography (OCT) allows for rapid non-invasive skin examination in the clinic. However, imaging depth at the popular 1300 nm wavelength is limited to ~1 mm due to scattering, making it difficult to assess severely inflamed skin. Skin optical properties, specifically scattering and absorption, vary with wavelength. Longer wavelengths centered at 1600 nm offer potential for deeper penetration due to lower scattering and minimal water absorption. Here we demonstrate a fiber-based, spectral-domain 1600 nm OCT system to study improvements in penetration depth in human skin. We use a supercontinuum laser source optimized for long-wavelength emission ranging from 1446 nm to 1694 nm to achieve high skin penetration depth, while maintaining an axial resolution of ~8-10 μm in the tissue (for the refractive index ranging n = 1.35 to 1.55 for different skin layers). Our system sensitivity is -90 dB at an A-scan rate of 76 kHz and approximately 8 mW of optical power on the skin. Simultaneous B-scans from a semi-transparent tape and human skin were obtained at 1600 nm and 1300 nm wavelengths, demonstrating and quantifying improvements in the imaging depth.
Atopic dermatitis, characterized by itchiness and inflammation, often results in increased skin thickness. Traditional treatments with topical corticosteroids may compound this effect. Addressing the need for accurate epidermal measurement and the slow acquisition times of previous methods, we have developed a high-speed OCT system utilizing a 1.67 MHz Fourier-domain Mode-locked (FDML) and a MEMS scanner, providing a 3 kHz frame rate. The measured axial and lateral resolutions are 13-14 μm and 35 μm in air, respectively. We have tested our system on the dorsal skin of human hands in vivo, targeting a volume scan of 2.8 x 2.8 x 5 mm3. The acquisition from the digitizer to PC memory only takes 0.1 seconds. To assess the epidermal thickness, we have developed an automatic segmentation algorithm for the detection of the skin surface and epidermal-dermal junction. The results indicate that the epidermal thickness is mostly between 110 to 150 μm on healthy dorsal hand skin. Additionally, we have generated an epidermal thickness map overlaying the enface skin image, providing a comprehensive view of the skin's structural integrity.
Atopic dermatitis (AD) often induces vasodilation, potentially impacting the velocity of blood flow within capillaries and vessels. To quantify the velocity change, we have developed and tested a 1.67 MHz 1310 nm Fourier-domain mode-locked (FDML) OCT system for measuring the decorrelation coefficient in blood vessels. This system provides an inter-frame time of 0.33 milliseconds and an A-scan spacing of 10 microns. A flow phantom, comprising a glass capillary tube of 80 μm inner diameter infused with unhomogenized milk by a syringe pump, was designed to test our OCT system mimicking the blood vessel. We collected 280 sequential B-scans at the same Y position of the phantom for a number of the velocity values. Based on variable interscan time analysis (VISTA) processing, we observed a strong correlation between the calculated decorrelation coefficients and the predetermined flow velocities, spanning a range from 0.16 mm/s to 30 mm/s. These findings enable us to explore our clinical hypotheses with in vivo tests.
The leading global cause of death in children under the age of five is due to complications arising from Preterm Birth (PTB). Although it is not fully understood why PTB can happen spontaneously, it is known that the cervix’s collagen rich extracellular matrix remodels prior to both term and preterm labor. In vitro Polarization-Sensitive Optical Coherence Tomography (PS-OCT) has successfully imaged the distribution and 3D alignment of collagen in the cervix, as well as determined birefringence and measured cervical tissue depolarization in healthy tissue samples. The present investigation aims to expand on this research, by implementing in silico design, optimization, and simulation techniques for a PS-OCT probe to be used for human in vivo cervical scanning. The design considers patient comfort and clinical access as key parameters; ensuring the components are suitable for a colposcope-like probe and commercially available for quick and cost-effective manufacturing. To achieve these aims, the design benefits from using as few components as possible and limiting optical surface reflections. In this paper we demonstrate that with the use of a cemented Gradient Index (GRIN) relay system, a Field of View (FOV) of up to 6 mm can be achieved, with a back-coupling efficiency of over 73%, on-axis and at up to a 2° scanning angle. Although Huygens Point Spread Function (PSF) lateral resolution reached 81 μm, this paper demonstrates that manual adjustment and optimization of the components can increase this resolution to 12 μm, although at the expense of FOV width reduction. The simulated probe design was verified in preliminary experiments using an in-house built fiber-based OCT engine where high-quality OCT images with wide FOV were obtained from various samples, including healthy human skin.
Atopic dermatitis is a chronic, relapsing inflammatory skin disease, which has one of the highest prevalence rates in the world. It is widely believed to be driven by deficiencies in the skin barrier layer, which is provided by the stratum corneum. The stratum corneum thickness determines the absorption rate of topical treatments and may correlate with its barrier function of preventing allergen penetration. Here we demonstrate a free-space, portable Fourier domain visible-light optical coherence tomography (OCT) system to study the stratum corneum thickness (5-15 μm typically) in non-palmar human skin. We use a supercontinuum laser source, optimized for emission in the 500-700 nm range and achieve axial resolution of ~ 1 μm in tissue (for the refractive index n = 1.55 of the stratum corneum). Our system has ~ -85 dB sensitivity at an A-scan rate of 125 kHz and about 1 mW of optical power onto the skin. High-quality B-scans from various human skin sites are obtained, with a clearly resolved stratum corneum layer presenting as a hypoechogenic dark layer, similar to that found in palmar skin with traditional OCT systems.
We report a continuous wave room temperature quantum cascade laser operating in an external cavity in the Littrow configuration with a 10-facet polygon mirror rotating at 24,000 RPM. The quantum cascade laser emission is swept across ∼1520 – 1625 cm-1 wavenumber range in less than ~45 µs with a sweep repetition rate of 4 kHz. The measured maximum output power at the laser gain maximum, 15°C and 0.86 A driving current is ~90 mW; the estimated average output power across the 45 µs wavenumber sweep is ~50 mW. Through its sweep, the laser emits on the sequential Fabry-Perot longitudinal modes of the laser chip cavity with the mode separation of ~0.5 cm-1 . The linewidth of the emitting modes is less than ~0.15 cm-1 . Spectral measurements of the infrared absorption features of a 10 µm thick layer of acetophenone and water vapor in the air have demonstrated the capability of obtaining spectral data in less than 45 μs.
Mid-infrared optical coherence tomography (MIR OCT) has shown promise in the last few years in applications such as spectroscopy and non-destructive testing. Previously, we have successfully demonstrated a MIR swept-source OCT and measured its noise from three main sources: quantization noise from the ADC, shot noise from the detectors and relative intensity noise (RIN) of the laser. Of these sources, RIN places an upper limit on the SNR of swept-source OCT systems. We attempt to characterize RIN in greater depth and determine whether it can be reduced through normalization. The pulsed laser used (Block Engineering Lasertune) is tunable within the wavelength range of 5.4-12.8μm. The laser output was held at a fixed wavelength, repetition rate and pulse width. Each laser pulse was integrated to find its average power along the pulse duration. A Fourier transform of the result was used to calculate the ratio of the AC power to DC power, giving a value for RIN. By using a beamsplitter and aspheric lenses to carefully focus the beam onto two detectors (Vigo System’s PVMI-4TE), the two pulse trains can be normalized. Through normalization, RIN was reduced from -74dB/Hz to -92dB/Hz. Increasing the repetition rate and pulse width leads to a decrease in RIN, but an upper limit on the laser duty cycle constrains improvements to RIN via this method. As the swept laser has four integrated quantum cascade laser (QCL) chips, we also examine the effect of different emission wavelengths on RIN.
A swept-source optical coherence tomography (OCT) system is demonstrated in the mid-infrared region. A Michelson interferometric setup is illuminated by an external cavity quantum cascade laser (QCL), with a scanning frequency of 1 Hz. A-scans were collected using three different samples: a mirror, CaF2 coated with germanium on both of its surfaces, and CaF2 coated with germanium on the back side of the sample. These depth-profiles were used to mimic a tissue sample with multiple reflective boundaries. Fourier transformation of these interference fringes clearly showed the expected depths of reflection, allowing for the signal to noise ratio of the system to be determined.
Infrared spectroscopy is a highly attractive read-out technology for compositional analysis of biomedical specimens because of its unique combination of high molecular sensitivity without the need for exogenous labels. Traditional techniques such as FTIR and Raman have suffered from comparatively low speed and sensitivity however recent innovations are challenging this situation. Direct mid-IR spectroscopy is being speeded up by innovations such as MEMS-based FTIR instruments with very high mirror speeds and supercontinuum sources producing very high sample irradiation levels. Here we explore another possible method – external cavity quantum cascade lasers (EC-QCL’s) with high cavity tuning speeds (mid-IR swept lasers).
Swept lasers have been heavily developed in the near-infrared where they are used for non-destructive low-coherence imaging (OCT). We adapt these concepts in two ways. Firstly by combining mid-IR quantum cascade gain chips with external cavity designs adapted from OCT we achieve spectral acquisition rates approaching 1 kHz and demonstrate potential to reach 100 kHz. Secondly we show that mid-IR swept lasers share a fundamental sensitivity advantage with near-IR OCT swept lasers. This makes them potentially able to achieve the same spectral SNR as an FTIR instrument in a time x N shorter (N being the number of spectral points) under otherwise matched conditions. This effect is demonstrated using measurements of a PDMS sample.
The combination of potentially very high spectral acquisition rates, fundamental SNR advantage and the use of low-cost detector systems could make mid-IR swept lasers a powerful technology for high-throughput biomedical spectroscopy.
FTIR spectroscopy using a thermal light source has been the dominant method for obtaining infrared spectra since the 1950’s. Unfortunately the limited surface brightness and low spatial coherence of black-body radiators limits the spectral SNR in microspectroscopy and stand-off detection. Two recent innovations are addressing this problem a) FTIR instruments illuminated by high-spatial coherence broad-band supercontinuum sources and b) high spatial coherence narrow-band EC-QCL’s.
Here we ask whether these two approaches offer equivalent sensitivity. By noting an analogy with near-infrared optical coherence tomography we rigorously show that the high temporal coherence of the EC-QCL brings an additional, very large SNR advantage over an FTIR instrument illuminated by a supercontinuum source under otherwise matched conditions. Specifically if a spectrum containing N points is recorded by both instruments using the same illumination intensity and the same detector noise level, then the EC-QCL can deliver a given spectral SNR in a time xN shorter than the FTIR instrument. This factor can reach x100, potentially even x1000, in realistic applications.
We exploit the analogy with OCT further by developing a mid-infrared “swept laser”, using commercially available components, in which the tuning rate is much higher than in commercial EC-QCL devices. We use this swept laser to demonstrate the SNR advantage experimentally, using a custom-made EC-QCL spectrometer and PDMS polymer samples. We explore the potential upper limits on spectral acquisition rates, both from the fundamental kinetics of gain build-up in the external cavity and from likely mechanical limits on cavity tuning rates.
Near-infrared external cavity lasers with high tuning rates (“swept lasers”) have come to dominate the field of nearinfrared
low-coherence imaging of biological tissues. Compared with time-domain OCT, swept-source OCT a) replaces
slow mechanical scanning of a bulky reference mirror with much faster tuning of a laser cavity filter element and b)
provides a ×N (N being the number of axial pixels per A-scan) speed advantage with no loss of SNR.
We will argue that this striking speed advantage has not yet been fully exploited within biophotonics but will next make
its effects felt in the mid-infrared. This transformation is likely to be driven by recent advances in external cavity
quantum cascade lasers, which are the mid-IR counterpart to the OCT swept-source. These mid-IR sources are rapidly
emerging in the area of infrared spectroscopy. By noting a direct analogy between time-domain OCT and Fourier
Transform Infrared (FTIR) spectroscopy we show analytically and via simulations that the mid-IR swept laser can
acquire an infrared spectrum ×N (N being the number of spectral data points) faster than an FTIR instrument, using
identical detected flux levels and identical receiver noise.
A prototype external cavity mid-IR swept laser is demonstrated, offering a comparatively low sweep rate of 400 Hz over
60 cm-1 with 2 cm-1 linewidth, but which provides evidence that sweep rates of over a 100 kHz should be readily
achievable simply by speeding up the cavity tuning element.
Translating the knowledge and experience gained in near-IR OCT into mid-IR source development may result in sources
offering significant benefits in certain spectroscopic applications.
We review the development of high performance, short wavelength (3 μm < λ < 3.8 μm) quantum cascade lasers (QCLs)
based on the deep quantum well InGaAs/AlAsSb/InP materials system. Use of this system has enabled us to demonstrate
room temperature operation at λ ~ 3.1 μm, the shortest room temperature lasing wavelength yet observed for InP-based
QCLs. We demonstrate that significant performance improvements can be made by using strain compensated material
with selective incorporation of AlAs barriers in the QCL active region. This approach provides reduction in threshold
current density and increases the maximum optical power. In such devices, room-temperature peak output powers of up
to 20 W can be achieved at λ ~ 3.6 μm, with high peak powers of around 4 W still achievable as wavelength decreases to
3.3 μm.
We report the first realization of short wavelength (λ ~ 3.05 - 3.6 μm) lattice matched In0.53Ga0.47As/AlAs0.56Sb0.44/InP
quantum cascade lasers (QCLs). The highest-performance device (λ ~ 3.6μm) displays pulsed laser action for
temperatures up to 300 K. The shortest wavelength QCL (λ ≈ 3.05 μm) operates in pulsed mode at temperatures only up
to 110 K. The first feasibility study of the strain compensated InGaAs/AlAsSb/InP QCLs (λ ~ 4.1 μm) proves that the
lasers with increased indium fractions in the InGaAs quantum wells of 60 and 70% display no degradation compared
with the lattice matched devices having identical design. This strain compensated system, being of particular interest for
QCLs at λ <~ 3.5μm, provides increased energy separation between the Γ and X conduction band minima in the quantum
wells, thus decreasing possible carrier leakage from the upper laser levels by intervalley scattering. We also demonstrate
that the performance of strain compensated InGaAs/AlAsSb QCLs can be improved if AlAsSb barriers in the QCL
active region are replaced by AlAs layers. The introduction of AlAs is intended to help suppress compositional
fluctuations due to inter diffusion at the quantum well/barrier interfaces.
We report on the experimental study of the structural, electronic and thermal properties of state-of-art Sb-based quantum-cascade lasers (QCLs) operating in the range 4.3-4.9 µm. This information has been obtained by investigating the active region band-to-band photoluminescence signals, detected by means of an GaInAs-array detector. This technique allowed to probe the spatial distribution of conduction electrons as a function of the applied voltage and to correlate the quantum design of devices with their thermal performance. We demonstrate that electron transport in QCLs based on Sb-ternary barriers may be insufficient, thus affecting the tunneling of electrons and the electronic recycling and cascading scheme. Finally, we present the first measurement of the electronic and lattice temperatures and the electron-lattice coupling in Sb-based QCLs based on a quaternary-alloy. We extracted the thermal resistance (RL = 8.9 K/W) and the electrical power dependence of the electronic temperature (Re = 11.7 K/W) of Ga0.47In0.53As/Al0.62Ga0.38As1-xSbx structures operating at 4.9 µm, in the lattice temperature range 50 K - 80 K. The corresponding electron-lattice coupling constant ( = 10.8 Kcm2/kA) reflects the reduction of the electron-leakage channels associated with the use of a high conduction band-offset.
We report on the experimental study of the electronic and thermal properties in state of art Sb-based quantum-cascade lasers (QCLs) operating in the range 4.3-4.9 &mgr;m. This information has been obtained by investigating the band-to-band photoluminescence signals, detected by means of an InGaAs-array detector. This technique allowed to probe the spatial distribution of conduction electrons as a function of the applied voltage and to correlate the quantum design of devices with their thermal performance. We demonstrate that electron transport in these structures may be insufficient, thus affecting the tunneling of electrons and the electronic recycling and cascading scheme. Finally, we present the first measurement of the electronic and lattice temperatures and of the electron-lattice coupling in Sb-based QCLs based on a
quaternary-alloy. We extracted the thermal resistance (RL = 9.6 K/W) and the electrical power dependence of the
electronic temperature (Re = 12.5 K/W) of Ga0.47In0.53As/Al0.62Ga0.38As1-xSbx structures operating at 4.9 &mgr;m, in the lattice temperature range 60 K - 90 K. The corresponding electron-lattice coupling &agr;= 9.5 Kcm2/kA) reflects the efficient electronic cooling via optical phonon emission. The experimental normalized thermal resistance RL* = 3.9 Kxcm/W
demonstrates the beneficial use of quaternary thicker barriers in terms of device thermal management.
We report the realisation of spectroscopic broadband transmission experiments on quantum cascade lasers (QCLs)
under continuous wave operating conditions for drive currents up to laser threshold. This technique allows, for the first
time, spectroscopic study of light transmission through the waveguide of QCLs in a very broad spectral range (λ~1.5-12
μm), limited only by the detector response and by interband absorption in the materials used in the QCL cladding
regions. Waveguide transmittance spectra have been studied for both TE and TM polarization, for InGaAs/InAlAs/InP
QCLs with different active region designs emitting at 7.4 and 10μm. The transmission measurements clearly show the
depopulation of the lower laser levels as bias is increased, the onset and growth of optical amplification at the energy
corresponding to the laser transitions as current is increased towards threshold, and the thermal filling of the second
laser level and decrease of material gain at high temperatures. This technique also allows direct determination of key
parameters such as the exact temperature of the laser core region under operating conditions, as well as the modal gain
and waveguide loss coefficients.
The quantum cascade laser is a semiconductor light source based on resonant tunnelling and optical transitions between quantised conduction band states. In these devices the principles of operation are not based on the physical properties of the constituent materials, but arise from the layer sequence forming the heterostructure. The quantum design and the control of the layer thickness, down to an atomic mono-layer, allows one to ascribe into a semiconductor crystal, artificial potentials with the desired electronic energy levels and wavefunctions. In recent years the performance of quantum cascade lasers has improved markedly and this semiconductor technology is now an attractive choice for the fabrication of mid-far infrared lasers in a very wide spectral range (3.5-160 μm). At present, the best performances are reached at wavelength between 5-10 μm, but recent results on new material systems with deeper quantum wells are indicating that this technology will be soon available also in the 3-5 μm spectral region.
We report MOVPE-grown quantum cascade lasers with operating wavelengths between λ~7.5-9.5μm with threshold current densities as low as 2.4kA/cm2 at room temperature. Seven wafers grown for operation at ~9μm show a variation of just 3% in the superlattice periods obtained from X-ray analysis, and laser emission is observed from all wafers with a ~5meV spread of emission energies. Multimode Fabry-Perot and singlemode distributed feedback lasers have been fabricated, operating at λ~7.8μm at room temperature, corresponding with absorption lines in the infrared spectra of methane. In addition, we have produced a strain compensated MOVPE-grown quantum cascade laser operating at λ~4.5μm.
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