A New Photoacoustic Soot Spectrophone for Filter-Free Measurements of Black Carbon at 880 nm.

A new photoacoustic soot spectrometer (PASS) operating at 880 nm was developed, for the first time, for filter-free measurements of black carbon (BC). The performance of the developed PASS was characterized and evaluated using a reference aethalometer AE51 on incense smoke in the air. An excellent correlation on the measurement of incense smoke was found between the two instruments in comparison with a regression coefficient of 0.99. A 1 σ detection limit of 0.8 µg m-3 was achieved for BC measurement at a time resolution of 1 s. It can be further reduced to 0.1 µg m-3, using a longer integration time of 1 min.

Functional diversity for body actions in the mesencephalic locomotor region.

The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion. Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson's disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements. We identify two spatially intermingled glutamatergic populations separable by axonal projections, mouse genetics, neuronal activity profiles, and motor functions. Most spinally projecting MLR neurons encoded the full-body behavior rearing. Loss- and gain-of-function optogenetic perturbation experiments establish a function for these neurons in controlling body extension. In contrast, Rbp4-transgene-positive MLR neurons project in an ascending direction to basal ganglia, preferentially encode the forelimb behaviors handling and grooming, and exhibit a role in modulating movement. Thus, the MLR contains glutamatergic neuronal subpopulations stratified by projection target exhibiting roles in action control not restricted to locomotion.

Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets.

The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and sub-circuit assembly of PN neuron subsets in the cortico-cerebellar pathway.

A dual-gas sensor for simultaneous detection of methane and acetylene based on time-sharing scanning assisted wavelength modulation spectroscopy.

Methane (CH4) and acetylene (C2H2) are important bioscience and chemical gases. The real-time monitoring and analysis of them have important research value in industrial process control. The time-sharing scanning assisted wavelength modulation spectroscopy (WMS) technique is developed for real-time and simultaneous detection of CH4 and C2H2. This system involves two near-infrared distributed feedback (DFB) lasers and a compact multipass cavity with an effective optical path of 52.2 m. The selected strong absorption lines of methane and acetylene are located at 6046.96 cm-1 and 6531.7 cm-1, respectively. The experiment environment is conducted at room temperature 23 °C and pressure 760 Torr. The sensor performance, including the minimum detection limit (MDL) and the stability, was improved by eliminating the influence of light intensity fluctuation using the WMS-2f/SAW technique. Allan deviation analysis indicates that a MDL of 0.1 ppm for CH4 and 0.2 ppm for C2H2 are achieved with 1-s integration time. And the instrument response time is about 44 s through the continuous analysis of standard gases. This sensitive, simple, reliable, and lowcost dual-gas sensor is very suitable for applications in the field environment, chemical process, and many other gas-phase analysis areas.

Analysis of the Stable Isotope Ratios (18O/16O, 17O/16O, and D/H) in Glacier Water by Laser Spectrometry.

A compact isotope ratio sensor based on laser absorption spectroscopy at 2.7 µm was developed for high precision and simultaneous measurements of the D/H, 18O/16O and 17O/16O isotope ratios in glacier water. Measurements of the oxygen and hydrogen isotope ratios in glacier water demonstrate a 1σ precision of 0.3‰ for δ18O, 0.2‰ for δ17O, and 0.5‰ for δ2H, respectively. The δ values of the working standard glacier water obtained by the calibrated sensor system is basically identical to the IRMS measurement results with a very high calibration accuracy from 0.17‰ to 0.75‰. Preliminary results on the reproducibility measurements display a standard deviation of 0.13‰ for δ18O, 0.13‰ for δ17O, and 0.64‰ for δ2H, respectively.

Salivary Fingerprinting of Periodontal Disease by Infrared-ATR Spectroscopy.

PURPOSE: Periodontal diseases, the most common chronic inflammatory diseases in humans, do not only affect tooth-supporting tissues but also other body parts by contributing to the development of life-threatening conditions. Since currently available diagnostic methods in periodontics lack the ability to identify patients at high risk for periodontal disease progression, development of innovative, non-invasive, rapid detection methods for diagnosing periodontal diseases is needed. This study aims to assess the potential of infrared attenuated total reflection (IR-ATR) spectroscopy to detect differences in composition of saliva supernatant in non-periodontitis individuals (control) and patients with generalized aggressive periodontitis (G-AgP). EXPERIMENTAL DESIGN: IR-ATR is performed with a wavelength interval from 1230 to 1180 cm-1 , analyzed with a simple subtraction in absorbance data. RESULTS: Ten samples show in the analysis of variance of the two data sets a true difference (99.8%). A principal component analysis (PCA) is able to discriminate between G-AgP and control groups. CONCLUSION AND CLINICAL RELEVANCE: This study demonstrates for the first time that IR-ATR spectroscopy is a promising tool for the analysis of saliva supernatant for the diagnosis of periodontitis, and potentially other periodontal conditions. IR-ATR spectroscopy holds the potential to be miniaturized and utilized as a non-invasive screening test.

Mid-Infrared Photoacoustic Detection of Glucose in Human Skin: Towards Non-Invasive Diagnostics.

Diabetes mellitus is a widespread metabolic disease without cure. Great efforts are being made to develop a non-invasive monitoring of the blood glucose level. Various attempts have been made, including a number of non-optical approaches as well as optical techniques involving visible, near- and mid-infrared light. However, no true breakthrough has been achieved so far, i.e., there is no fully non-invasive monitoring device available. Here we present a new study based on mid-infrared spectroscopy and photoacoustic detection. We employ two setups, one with a fiber-coupled photoacoustic (PA) cell and a tunable quantum cascade laser (QCL), and a second setup with two QCLs at different wavelengths combined with PA detection. In both cases, the PA cells are in direct skin contact. The performance is tested with an oral glucose tolerance test. While the first setup often gives reasonable qualitative agreement with ordinary invasive blood glucose measurements, the dual-wavelength approach yields a considerably improved stability and an uncertainty of only ±30 mg/dL of the blood glucose concentration level at a confidence level of 90%. This result is achieved without advanced data treatment such as principal component analysis involving extended wavelength ranges.

Development of a tunable diode laser absorption sensor for online monitoring of industrial gas total emissions based on optical scintillation cross-correlation technique.

We report the first application of gas total emission using a DFB diode laser for gas concentration measurements combined with two LEDs for gas velocity measurements. In situ gas total emissions and particle density measurements in an industrial pipeline using simultaneous tunable diode laser absorption spectroscopy (TDLAS) and optical scintillation cross-correlation technique (OSCC) are presented. Velocity mean values obtained are 7.59 m/s (OSCC, standard deviation is 1.37 m/s) and 8.20 m/s (Pitot tube, standard deviation is 1.47 m/s) in a steel plant pipeline for comparison. Our experiments demonstrate that the combined system of TDLAS and OSCC provides a new versatile tool for accurate measurements of total gas emissions.

Fire Source Localization Based on Distributed Temperature Sensing by a Dual-Line Optical Fiber System.

We propose a method for localizing a fire source using an optical fiber distributed temperature sensor system. A section of two parallel optical fibers employed as the sensing element is installed near the ceiling of a closed room in which the fire source is located. By measuring the temperature of hot air flows, the problem of three-dimensional fire source localization is transformed to two dimensions. The method of the source location is verified with experiments using burning alcohol as fire source, and it is demonstrated that the method represents a robust and reliable technique for localizing a fire source also for long sensing ranges.

Multisensory Signaling Shapes Vestibulo-Motor Circuit Specificity.

The ability to continuously adjust posture and balance is necessary for reliable motor behavior. Vestibular and proprioceptive systems influence postural adjustments during movement by signaling functionally complementary sensory information. Using viral tracing and mouse genetics, we reveal two patterns of synaptic specificity between brainstem vestibular neurons and spinal motor neurons, established through distinct mechanisms. First, vestibular input targets preferentially extensor over flexor motor pools, a pattern established by developmental refinement in part controlled by vestibular signaling. Second, vestibular input targets slow-twitch over fast motor neuron subtypes within extensor pools, while proprioceptors exhibit inversely correlated connectivity profiles. Genetic manipulations affecting the functionality of proprioceptive feedback circuits lead to adjustments in vestibular input to motor neuron subtypes counterbalancing the imposed changes, without changing the sparse vestibular input to flexor pools. Thus, two sensory signaling systems interact to establish complementary synaptic input patterns to the final site of motor output processing.

Mid-infrared laser-spectroscopic sensing of chemical species.

This letter reports on mid-infrared laser-based detection and analysis of chemical species. Emphasis is put on broadly tunable laser sources and sensitive detection schemes. Selected examples from our lab illustrate the performance and potential of such systems in various areas including environmental and medical sensing.

Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement.

Quantitative chemical analysis of surgical smoke generated during laparoscopic surgery with a vessel-sealing device.

BACKGROUND: Exposure to surgical smoke in the operation room has been a long-standing concern. Smoke generated by the interaction between lasers or electrocautery devices with biological tissue contains several toxic and carcinogenic substances, but only a few studies so far have provided quantitative data necessary for risk assessment. METHODS: With laser and Fourier-transform infrared spectroscopy, we investigated the chemical composition of smoke produced with a vessel-sealing device in an anoxic environment during laparoscopic surgery. RESULTS: Harmless concentrations of methane (<34 ppm), ethane (<2 ppm), and ethylene (<10 ppm) were detected. Traces of carbon monoxide (<3.2 ppm) and of the anesthetic sevoflurane (<450 ppm) were also found. CONCLUSIONS. Gas leaking or gas being released from the pneumoperitoneum could therefore increase pollution by waste anesthetic gas in the operating room. Most toxic compounds found in earlier studies remained undetected. Adverse health effects for operating room personnel due to some of those substances (e.g., toluene, styrene, xylene) can be excluded, assuming no significant losses or changes in the chemical composition of the samples occurred between our sampling and measurements.

The organization of submodality-specific touch afferent inputs in the vibrissa column.

The rodent tactile vibrissae are innervated by several different types of touch sensory neurons. The central afferents of all touch neurons from one vibrissa collectively project to a columnar structure called a barrelette in the brainstem. Delineating how distinct types of sensors connect to second-order neurons within each barrelette is critical for understanding tactile information coding and processing. Using genetic and viral techniques, we labeled slowly adapting (SA) mechanosensory neurons, rapidly adapting (RA) mechanosensory neurons, afferent synapses, and second-order projection neurons with four different fluorescent markers to examine their connectivity. We discovered that within each vibrissa column, individual sensory neurons project collaterals to multiply distributed locations, inputs from SA and RA afferents are spatially intermixed without any discernible stereotypy or topography, and second-order projection neurons receive convergent SA and RA inputs. Our findings reveal a "one-to-many and many-to-one" connectivity scheme and the circuit architecture for tactile information processing at the first-order synapses.

Microfluidic droplet-based liquid-liquid extraction and on-chip IR spectroscopy detection of cocaine in human saliva.

We present a portable microsystem to quantitatively detect cocaine in human saliva. In this system, we combine a microfluidic-based multiphase liquid-liquid extraction method to transfer cocaine continuously from IR-light-absorbing saliva to an IR-transparent solvent (tetrachloroethylene) with waveguide IR spectroscopy (QC-laser, waveguide, detector) to detect the cocaine on-chip. For the fabrication of the low-cost polymer microfluidic chips a simple rapid prototyping technique based on Scotch-tape masters was further developed and applied. To perform the droplet-based liquid-liquid extraction, we designed and integrated a simple and robust droplet generation method based on the capillary focusing effect within the device. Compared to well-characterized and commonly used microfluidic H-filters, our system showed at least two times higher extraction efficiencies with potential for further improvements. The current liquid-liquid extraction method alone can efficiently extract cocaine and pre-concentrate the analytes in a new solvent. Our fully integrated optofluidic system successfully detected cocaine in real saliva samples spiked with the drug (500 µg/mL) and allowed real time measurements, which makes this approach suitable for point-of-care applications.

Mid-infrared fiber-coupled photoacoustic sensor for biomedical applications.

Biomedical devices employed in therapy, diagnostics and for self-monitoring often require a high degree of flexibility and compactness. Many near infrared (NIR) optical fiber-coupled systems meet these requirements and are employed on a daily basis. However, mid-infrared (MIR) fibers-based systems have not yet found their way to routine application in medicine. In this work we present the implementation of the first MIR fiber-coupled photoacoustic sensor for the investigation of condensed samples in the MIR fingerprint region. The light of an external-cavity quantum-cascade laser (1010-1095 cm(-1)) is delivered by a silver halide fiber, which is attached to the PA cell. The PA chamber is conically shaped to perfectly match the beam escaping the fiber and to minimize the cell volume. This results in a compact and handy sensor for investigations of biological samples and the monitoring of constituents both in vitro and in vivo. The performance of the fiber-coupled PA sensor is demonstrated by sensing glucose in aqueous solutions. These measurements yield a detection limit of 57 mg/dL (SNR = 1). Furthermore, the fiber-coupled sensor has been applied to record human skin spectra at different body sites to illustrate its flexibility.

Scaling proprioceptor gene transcription by retrograde NT3 signaling.

Cell-type specific intrinsic programs instruct neuronal subpopulations before target-derived factors influence later neuronal maturation. Retrograde neurotrophin signaling controls neuronal survival and maturation of dorsal root ganglion (DRG) sensory neurons, but how these potent signaling pathways intersect with transcriptional programs established at earlier developmental stages remains poorly understood. Here we determine the consequences of genetic alternation of NT3 signaling on genome-wide transcription programs in proprioceptors, an important sensory neuron subpopulation involved in motor reflex behavior. We find that the expression of many proprioceptor-enriched genes is dramatically altered by genetic NT3 elimination, independent of survival-related activities. Combinatorial analysis of gene expression profiles with proprioceptors isolated from mice expressing surplus muscular NT3 identifies an anticorrelated gene set with transcriptional levels scaled in opposite directions. Voluntary running experiments in adult mice further demonstrate the maintenance of transcriptional adjustability of genes expressed by DRG neurons, pointing to life-long gene expression plasticity in sensory neurons.

Wnt7A identifies embryonic γ-motor neurons and reveals early postnatal dependence of γ-motor neurons on a muscle spindle-derived signal.

Motor pools comprise a heterogeneous population of motor neurons that innervate distinct intramuscular targets. While the organization of motor neurons into motor pools has been well described, the time course and mechanism of motor pool diversification into functionally distinct classes remains unclear. γ-Motor neurons (γ-MNs) and α-motor neurons (α-MNs) differ in size, molecular identity, synaptic input and peripheral target. While α-MNs innervate extrafusal skeletal muscle fibers to mediate muscle contraction, γ-MNs innervate intrafusal fibers of the muscle spindle, and regulate sensitivity of the muscle spindle in response to stretch. In this study, we find that the secreted signaling molecule Wnt7a is selectively expressed in γ-MNs in the mouse spinal cord by embryonic day 17.5 and continues to molecularly distinguish γ-from α-MNs into the third postnatal week. Our data demonstrate that Wnt7a is the earliest known γ-MN marker, supporting a model of developmental divergence between α- and γ-MNs at embryonic stages. Furthermore, using Wnt7a expression as an early marker of γ-MN identity, we demonstrate a previously unknown dependence of γ-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week.

Glucose sensing in human epidermis using mid-infrared photoacoustic detection.

No reliable non-invasive glucose monitoring devices are currently available. We implemented a mid-infrared (MIR) photoacoustic (PA) setup to track glucose in vitro in deep epidermal layers, which represents a significant step towards non-invasive in vivo glucose measurements using MIR light. An external-cavity quantum-cascade laser (1010-1095 cm(-1)) and a PA cell of only 78 mm(3) volume were employed to monitor glucose in epidermal skin. Skin samples are characterized by a high water content. Such samples investigated with an open-ended PA cell lead to varying conditions in the PA chamber (i.e., change of light absorption or relative humidity) and cause unstable signals. To circumvent variations in relative humidity and possible water condensation, the PA chamber was constantly ventilated by a 10 sccm N(2) flow. By bringing the epidermal skin samples in contact with aqueous glucose solutions with different concentrations (i.e., 0.1-10 g/dl), the glucose concentration in the skin sample was varied through passive diffusion. The achieved detection limit for glucose in epidermal skin is 100 mg/dl (SNR=1). Although this lies within the human physiological range (30-500 mg/dl) further improvements are necessary to non-invasively monitor glucose levels of diabetes patients. Furthermore spectra of epidermal tissue with and without glucose content have been recorded with the tunable quantum-cascade laser, indicating that epidermal constituents do not impair glucose detection.

Infrared attenuated total reflection (IR-ATR) spectroscopy for detecting drugs in human saliva.

The consumption of drugs is of great concern worldwide. Various drug tests for humans have been developed but there is no compact and easy-to-use test device available yet for direct semi-quantitative drug testing in the field. We suggest using attenuated total reflection (ATR) infrared spectroscopy as a sensing method to analyze human saliva samples with respect to drugs. In this paper, we present ATR spectra in the infrared range between 2300 and 900 cm(-1) as a first step towards such a device. We emphasize the common drug cocaine and its metabolites and investigate the problems of spectral interferences of selected diluents, masking agents, common medication, and soft drinks. Furthermore, spectra of saliva samples are recorded and a time-dependent change of the spectral signatures after alcohol consumption is presented. To the best of our knowledge, it is the first time that not only spectra of the drug of interest (cocaine) dissolved in water and in saliva but also spectra of interfering compounds possibly present in the saliva sample of a tested subject are discussed. This paper presents the most appropriate spectral range for strong cocaine absorption (including its metabolites) and minimum interference by the investigated substances. This spectral window is found to be between 1800 and 1710 cm(-1). In addition, we demonstrate the feasibility to identify cocaine in saliva at a concentration of 0.020 mg/ml with IR-ATR-spectroscopy without any separation or extraction procedures. For example, this technique could also be applied for drug detection in waste water.