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Obituary: Professor David Smith. 讣告:大卫·史密斯教授。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-04-24 DOI: 10.1088/1752-7163/acca3d
Patrik Španěl, Terence H Risby
Professor David Smith, PhD, FRS, passed away peacefully at home on 15 February 2023. Professor David Smith, one of nine children, was born 1935 in Stoke-on-Trent, UK. He was educated in physics and chemistry that resulted in his interest in gas discharge physics and this combined with a unique vision and inventiveness made him a leading figure in the experimental investigations of gas phase electron and ion chemistry. Among other achievements, he is known as the originator of the selected ion flow tube (SIFT) technique for the study of the kinetics of reactions of ions with molecules occurring in the interstellar space in the mid-1970s. Using this technique he studied with colleagues thousands of ion-molecule rate coefficients, most of which he kept in his phenomenal memory all of his life. This was a foundation for the development of the SIFT-MS analytical technique some 20 years later, which is now widely known in the breath gas community as one of the online tools for the quantification of breath gas constituents. In 1996, David wrote the first article detailing the utility of SIFT-MS for the quantitative and sensitive analysis of trace gases in breath. Today the breath gas literature is replete with articles reporting on breath-related studies employing SIFTMS. David Smith’s publications clearly illustrate his impact on the development of breath research over the past three decades. David was a founding member of the International Association of Breath Research (IABR), and a founding editorial board member of this journal. David’s unique contribution to breath analysis was his pioneering studies using SIFT-MS to measure the concentration of targeted volatile metabolites in breath in real-time. This approach provides quantitative information on the abundance of small molecules in breath that could not be observed in offline analyses of collected breath samples. His research was recognized nationally and internationally by many awards, notably election as a fellow of the Royal Society, London, UK,Honorary DSc, University of Keele, and most recently the Heyrovsky medal from the Czech Academy of Sciences. Additionally, a special issue of Journal of Breath Researchwas published in 2014 (J. BreathRes. 8 (2014) 030201) in recognition of David’s substantial contributions to the field of breath gas analysis. The breath research community will miss David for his unique contributions, critical approach to science, insight, vision and for his role in evocative discussions during international breath research meetings.
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引用次数: 0
A review on isoprene in human breath. 人呼吸中异戊二烯的研究进展。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-04-19 DOI: 10.1088/1752-7163/acc964
Paweł Mochalski, Julian King, Chris A Mayhew, Karl Unterkofler
We summarize the history and review the literature on isoprene in exhaled breath and discuss the current evidence and models that describe its endogenous origin and consequence for understanding isoprene levels and their variations in exhaled breath.
我们总结了呼出气中异戊二烯的历史和文献,并讨论了当前的证据和模型,描述了其内源性起源和理解异戊二烯水平及其在呼出气中的变化的后果。
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引用次数: 3
In vitro-in vivocorrelation of aerosol deposition before and after metered-dose inhaler coaching in healthy children. 健康儿童计量吸入器训练前后气溶胶沉积的体内外相关性
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-04-13 DOI: 10.1088/1752-7163/acc8f1
Michael D Davis, Jessica L Saunders, Coral Ringer, Rebecca Engberg, Yi Zhao, Robert M DiBlasi, Bruce K Rubin

Although pressurized metered dose inhaler (pMDI) education is a routine part of childhood asthma management and encouraging 'optimal breathing patterns' (i.e. slowly, deeply, completely, and with a mouth seal on the mouthpiece) is an integral part of recommended pMDI education, there is currently no quantifiable way to determine if a child is inhaling their medication correctly or optimally through a valved holding chamber (VHC). The TipsHaler™ (tVHC) is a prototype VHC device that measures inspiratory time, flow, and volume without changing the properties of the medication aerosol. The measurementsin vivorecorded by the tVHC can be downloaded and transferred to a spontaneous breathing lung model to simulate the inhalational patternsin vitroand also determine the deposition of inhaled aerosol mass with each pattern. We hypothesized that pediatric patients' inhalational patterns when using a pMDI would improve after active coaching via tVHC. This would increase the pulmonary deposition of inhaled aerosols in anin vitromodel. To test this hypothesis, we conducted a single-site, prospective, pilot, pre-and-post intervention study paired with a bedside-to-bench experiment. Healthy, inhaler-naïve subjects used a placebo inhaler in conjunction with the tVHC before and after coaching and recorded inspiratory parameters. These recordings were then implemented into a spontaneous breathing lung model during albuterol MDI delivery, and pulmonary deposition of albuterol was quantified. In this pilot study, active coaching resulted in a statistically significant increase in inspiratory time (n= 8,p= 0.0344, 95%CI: 0.082 to ∞). tVHC recorded inspiratory parameters obtained from patients were successfully implemented in thein vitromodel, which demonstrated that both inspiratory time (n= 8,r= 0.78,p <0.001, 95%CI: 0.47-0.92) and volume (n= 8,r= 0.58,p =0.0186, 95%CI: 0.15-0.85) strongly correlate with pulmonary deposition of inhaled drugs.

虽然加压计量吸入器(pMDI)教育是儿童哮喘管理的常规组成部分,鼓励“最佳呼吸模式”(即缓慢、深度、完全,并将口封在吸口上)是推荐的pMDI教育的组成部分,但目前没有可量化的方法来确定儿童是否正确或最佳地通过有阀保持室(VHC)吸入药物。TipsHaler™(tVHC)是一种原型VHC设备,可在不改变药物气溶胶特性的情况下测量吸入时间,流量和体积。由tVHC记录的体内测量数据可下载并转移到一个自主呼吸肺模型中,以模拟体外的吸入模式,并确定吸入的气溶胶在每种模式下的沉积情况。我们假设儿科患者在使用pMDI时的吸入模式会在通过tVHC进行积极指导后得到改善。在体外模型中,这将增加吸入气溶胶的肺沉积。为了验证这一假设,我们进行了一项单站点、前瞻性、试点、干预前和干预后研究,并进行了一项床边到工作台的实验。健康的inhaler-naïve受试者在训练前后使用安慰剂吸入器和tVHC,并记录吸气参数。然后将这些记录应用于沙丁胺醇MDI输送过程中的自发性呼吸肺模型,并量化沙丁胺醇的肺沉积。在本初步研究中,积极训练导致吸气时间显著增加(n= 8,p= 0.0344, 95%CI: 0.082至∞)。tVHC记录的患者吸气参数成功地应用于体外模型,结果表明,吸气时间(n= 8,r= 0.78,p = 0.001, 95%CI: 0.47-0.92)和体积(n= 8,r= 0.58,p =0.0186, 95%CI: 0.15-0.85)与吸入药物的肺沉积密切相关。
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引用次数: 0
Breath analysis by ultra-sensitive broadband laser spectroscopy detects SARS-CoV-2 infection. 利用超灵敏宽带激光光谱进行呼气分析可检测出 SARS-CoV-2 感染。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-04-05 DOI: 10.1088/1752-7163/acc6e4
Qizhong Liang, Ya-Chu Chan, Jutta Toscano, Kristen K Bjorkman, Leslie A Leinwand, Roy Parker, Eva S Nozik, David J Nesbitt, Jun Ye

Rapid testing is essential to fighting pandemics such as coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exhaled human breath contains multiple volatile molecules providing powerful potential for non-invasive diagnosis of diverse medical conditions. We investigated breath detection of SARS-CoV-2 infection using cavity-enhanced direct frequency comb spectroscopy (CE-DFCS), a state-of-the-art laser spectroscopic technique capable of a real-time massive collection of broadband molecular absorption features at ro-vibrational quantum state resolution and at parts-per-trillion volume detection sensitivity. Using a total of 170 individual breath samples (83 positive and 87 negative with SARS-CoV-2 based on reverse transcription polymerase chain reaction tests), we report excellent discrimination capability for SARS-CoV-2 infection with an area under the receiver-operating-characteristics curve of 0.849(4). Our results support the development of CE-DFCS as an alternative, rapid, non-invasive test for COVID-19 and highlight its remarkable potential for optical diagnoses of diverse biological conditions and disease states.

快速检测对于抗击流行病至关重要,例如由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)。人体呼出的气体中含有多种挥发性分子,为无创诊断各种疾病提供了强大的潜力。我们研究了利用腔增强直接频率梳光谱(CE-DFCS)对 SARS-CoV-2 感染进行呼气检测的方法。CE-DFCS 是一种最先进的激光光谱技术,能够实时大量收集宽带分子吸收特征,具有罗振量子态分辨率和万亿分之一体积检测灵敏度。通过对 170 份个体呼气样本(根据反转录聚合酶链反应测试,SARS-CoV-2 阳性样本 83 份,阴性样本 87 份)的研究,我们发现该技术对 SARS-CoV-2 感染具有极佳的分辨能力,接收者工作特征曲线下面积为 0.849(4)。我们的研究结果支持开发 CE-DFCS 作为 COVID-19 的替代性、快速、非侵入性检测方法,并凸显了它在不同生物条件和疾病状态的光学诊断方面的巨大潜力。
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引用次数: 0
A review on electronic nose for diagnosis and monitoring treatment response in lung cancer. 电子鼻在肺癌诊断及治疗反应监测中的研究进展。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-03-27 DOI: 10.1088/1752-7163/acb791
Rohit Vadala, Bijay Pattnaik, Sunil Bangaru, Divyanjali Rai, Jaya Tak, Seetu Kashyap, Umashankar Verma, Geetika Yadav, R S Dhaliwal, Saurabh Mittal, Vijay Hadda, Karan Madan, Randeep Guleria, Anurag Agrawal, Anant Mohan

Lung cancer is one of the common malignancies with high mortality rate and a poor prognosis. Most lung cancer cases are diagnosed at an advanced stage either due to limited resources of infrastructure, trained human resources, or delay in clinical suspicion. Low-dose computed tomography has emerged as a screening tool for lung cancer detection but this may not be a feasible option for most developing countries. Electronic nose is a unique non-invasive device that has been developed for lung cancer diagnosis and monitoring response by exhaled breath analysis of volatile organic compounds. The breath-print have been shown to differ not only among lung cancer and other respiratory diseases, but also between various types of lung cancer. Hence, we postulate that the breath-print analysis by electronic nose could be a potential biomarker for the early detection of lung cancer along with monitoring treatment response in a resource-limited setting. In this review, we have consolidated the current published literature suggesting the use of an electronic nose in the diagnosis and monitoring treatment response of lung cancer.

肺癌是常见的恶性肿瘤之一,死亡率高,预后差。由于基础设施资源有限、受过培训的人力资源有限或临床怀疑延误,大多数肺癌病例在晚期才被诊断出来。低剂量计算机断层扫描已成为肺癌检测的一种筛查工具,但对大多数发展中国家来说,这可能不是一种可行的选择。电子鼻是一种独特的非侵入性设备,已开发用于肺癌诊断和监测反应,通过呼气分析挥发性有机化合物。研究表明,呼吸指纹不仅在肺癌和其他呼吸系统疾病之间存在差异,而且在不同类型的肺癌之间也存在差异。因此,我们假设电子鼻的呼吸指纹分析可能是一种潜在的生物标志物,可以在资源有限的情况下早期发现肺癌,并监测治疗反应。在这篇综述中,我们整合了目前发表的建议使用电子鼻诊断和监测肺癌治疗反应的文献。
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引用次数: 1
Assessment of an e-nose performance for the detection of COVID-19 specific biomarkers. 评估用于检测COVID-19特异性生物标志物的电子鼻性能
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-02-16 DOI: 10.1088/1752-7163/acb9b2
Christelle Ghazaly, Krystyna Biletska, Etienne A Thevenot, Philippe Devillier, Emmanuel Naline, Stanislas Grassin-Delyle, Emmanuel Scorsone

Early, rapid and non-invasive diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is needed for the prevention and control of coronavirus disease 2019 (COVID-19). COVID-19 mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening. In the current study, an experimental protocol using an electronic-nose ('e-nose') for attempting to identify a specific respiratory imprint in COVID-19 patients was optimized. Thus the analytical performances of the Cyranose®, a commercial e-nose device, were characterized under various controlled conditions. In addition, the effect of various experimental conditions on its sensor array response was assessed, including relative humidity, sampling time and flow rate, aiming to select the optimal parameters. A statistical data analysis was applied to e-nose sensor response using common statistical analysis algorithms in an attempt to demonstrate the possibility to detect the presence of low concentrations of spiked acetone and nonanal in the breath samples of a healthy volunteer. Cyranose®reveals a possible detection of low concentrations of these two compounds, in particular of 25 ppm nonanal, a possible marker of SARS-CoV-2 in the breath.

预防和控制2019冠状病毒病(COVID-19)需要对严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染进行早期、快速和无创诊断。COVID-19主要影响呼吸道和肺部。因此,呼气分析可能是可靠的SARS-CoV-2筛查的一种可扩展的替代方法。在目前的研究中,优化了一种使用电子鼻(“电子鼻”)试图识别COVID-19患者特定呼吸印记的实验方案。因此,商用电子鼻装置Cyranose®的分析性能在各种控制条件下进行了表征。此外,还评估了相对湿度、采样时间和流量等不同实验条件对其传感器阵列响应的影响,以选择最优参数。利用常见的统计分析算法对电子鼻传感器响应进行了统计数据分析,试图证明在健康志愿者的呼吸样本中检测到低浓度的加药丙酮和壬醛的可能性。Cyranose®显示可能检测到低浓度的这两种化合物,特别是25 ppm的壬醛,这可能是呼吸中SARS-CoV-2的标志。
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引用次数: 0
Validation of the fractional exhaled breath temperature measurement: reference values. 分数呼气温度测量的验证:参考值。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-02-10 DOI: 10.1088/1752-7163/acb598
Ivana Huljev Šipoš, Kristijan Šipoš, Justinija Steiner, Petra Grubić Rotkvić, Đivo Ljubičić, Ana Marija Šola, Emilija Lozo Vukovac, Tatjana Kereš, Davor Plavec

Exhaled breath temperature (EBT) is a known biomarker of inflammation and airways blood flow. As opposed to previous studies, we were able to measure temperature of separate fractions of exhaled breath (fEBT) (those from the peripheral and central airways). The aim was to validate the fEBT measurement method to determine the reference values and the influence of endogenous and exogenous factors on fEBT in healthy subjects. This cross-sectional study included 55 healthy adults in whom fEBT was repeatedly measured, two days in a row, using a FractAir®device. Also, basal metabolic rate, level of physical activity, distance from the main road, outdoor and ambient temperature, air pressure and humidity, haematology and inflammation markers, lung function, cumulative EBT and body temperature at characteristic points on the body were measured. The results showed that fEBT from central airways was lower compared to fEBT from the periphery and that fEBTs were not related to body temperature (p> 0.05 for all). We also showed repeatability of fEBT measurements for two consecutive days. All EBT fractions correlated significantly with ambient temperature (<0.01). No associations of fEBT with other personal and external factors were found using multivariate analysis. At room temperature of 22 °C, the physiological temperature values of the first fraction were 23.481 ± 3.150 °C, the second fraction 26.114 ± 4.024 °C and the third fraction 28.216 ± 3.321 °C. The proposed reference values represent the first part of validation of fEBT as the method for the use in clinical practice.

呼气温度(EBT)是炎症和气道血流的已知生物标志物。与之前的研究相反,我们能够测量呼出气体(fEBT)的不同部分(来自外周和中央气道)的温度。目的是验证fEBT测量方法,确定参考值以及内源性和外源性因素对健康受试者fEBT的影响。这项横断面研究包括55名健康成年人,使用FractAir®设备连续两天反复测量他们的fEBT。此外,还测量了基础代谢率、体力活动水平、与主要道路的距离、室外和环境温度、气压和湿度、血液学和炎症指标、肺功能、累积EBT和身体特征点的体温。结果表明,中央气道fEBT低于外周气道fEBT,且与体温无关(p> 0.05)。我们还显示了连续两天fEBT测量的可重复性。所有EBT分数与环境温度(
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引用次数: 0
Extracellular vesicles-derived miRNAs as mediators of pulmonary exacerbation in pediatric cystic fibrosis. 细胞外囊泡来源的mirna作为儿童囊性纤维化肺恶化的介质。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-02-10 DOI: 10.1088/1752-7163/acb792
Zuzanna Stachowiak, Irena Wojsyk-Banaszak, Katarzyna Jończyk-Potoczna, Beata Narożna, Wojciech Langwiński, Aleksandra Szczepankiewicz

Children with cystic fibrosis (CF) suffer from chronic inflammation and recurrent pulmonary exacerbations (PEs). We aimed to test whether a specific miRNA could be associated with the occurrence of PE. We sequenced extracellular vesicle (EV)-derived miRNA in sputum (n= 20), exhaled breath condensate (EBC) (n= 11), and serum (n= 8) samples from pediatric patients during PE and the stable stage of CF. Four miRNAs: let-7c, miR-16, miR-25-3p and miR-146a, have been selected for validation in a larger group with reverse transcription quantitative real-time PCR (RT-qPCR) in sputum and serum, or droplet digital PCR (ddPCR) in EBC. Next-generation sequencing (NGS) differential expression analysis was done in Base Space, and the correlation between miRNAs expression and clinical data was calculated with Statistica. Functional annotation of selected miRNAs and their potential target genes was performed with miRDip and DAVID software. There were no differences in miRNA expression between stable and exacerbation in sputum and in serum. Validation of four selected miRNAs showed significant downregulation of miR-146a in serum. A panel of all four miRNAs (peripherally) was the best predictive model of exacerbation (p< 0.001, AUC = 0.96). Expression of airway miR-25-3p improved the diagnostic value of FEV1% pred and FVC% pred, while peripheral miR-146a improved the predictive model of C-reactive protein and neutrophilia.In silicoanalysis revealed a potential role for selected miRNAs in regulating processes associated with inflammation and tissue remodeling. We demonstrated that EVs contained in peripheral blood as well as local biomaterials can act as carriers for miRNAs with the diagnostic potential of predicting exacerbation in pediatric CF.

患有囊性纤维化(CF)的儿童患有慢性炎症和复发性肺恶化(PEs)。我们的目的是测试一个特定的miRNA是否与PE的发生有关。我们对来自PE和CF稳定期儿科患者的痰(n= 20)、呼气冷凝水(n= 11)和血清(n= 8)样本中的细胞外囊泡(EV)来源的miRNA进行了测序。我们选择了四种miRNA: let-7c、miR-16、miR-25-3p和miR-146a,通过痰和血清中的逆转录定量实时PCR (RT-qPCR)或EBC中的液滴数字PCR (ddPCR)在更大的群体中进行验证。在Base Space中进行下一代测序(NGS)差异表达分析,用Statistica计算miRNAs表达与临床数据的相关性。利用miRDip和DAVID软件对选定的mirna及其潜在靶基因进行功能注释。痰液和血清中miRNA的表达在稳定期和加重期无差异。对四个选定的mirna的验证显示血清中miR-146a的显著下调。所有四种mirna(外周)是病情恶化的最佳预测模型(p< 0.001, AUC = 0.96)。气道miR-25-3p的表达提高了FEV1% pred和FVC% pred的诊断价值,外周血miR-146a的表达提高了c反应蛋白和中性粒细胞的预测模型。硅分析揭示了选定的mirna在调节炎症和组织重塑相关过程中的潜在作用。我们证明,外周血和局部生物材料中含有的ev可以作为mirna的载体,具有预测儿童CF恶化的诊断潜力。
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引用次数: 0
Breath VOC analysis and machine learning approaches for disease screening: a review. 呼吸挥发性有机化合物分析和机器学习方法用于疾病筛查:综述。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-02-03 DOI: 10.1088/1752-7163/acb283
Haripriya P, Madhavan Rangarajan, Hardik J Pandya

Early disease detection is often correlated with a reduction in mortality rate and improved prognosis. Currently, techniques like biopsy and imaging that are used to screen chronic diseases are invasive, costly or inaccessible to a large population. Thus, a non-invasive disease screening technology is the need of the hour. Existing non-invasive methods like gas chromatography-mass spectrometry, selected-ion flow-tube mass spectrometry, and proton transfer reaction-mass-spectrometry are expensive. These techniques necessitate experienced operators, making them unsuitable for a large population. Various non-invasive sources are available for disease detection, of which exhaled breath is preferred as it contains different volatile organic compounds (VOCs) that reflect the biochemical reactions in the human body. Disease screening by exhaled breath VOC analysis can revolutionize the healthcare industry. This review focuses on exhaled breath VOC biomarkers for screening various diseases with a particular emphasis on liver diseases and head and neck cancer as examples of diseases related to metabolic disorders and diseases unrelated to metabolic disorders, respectively. Single sensor and sensor array-based (Electronic Nose) approaches for exhaled breath VOC detection are briefly described, along with the machine learning techniques used for pattern recognition.

早期发现疾病往往与降低死亡率和改善预后相关。目前,用于筛查慢性疾病的活检和成像等技术是侵入性的、昂贵的,或者对大量人群来说是难以获得的。因此,一种无创的疾病筛查技术是当务之急。现有的非侵入性方法,如气相色谱-质谱法、选择离子流管质谱法和质子转移反应-质谱法都是昂贵的。这些技术需要经验丰富的操作人员,因此不适合大量人群使用。疾病检测有多种非侵入性来源,其中呼气是首选,因为它含有不同的挥发性有机化合物(VOCs),反映了人体内的生化反应。通过呼气挥发性有机化合物分析进行疾病筛查可以彻底改变医疗保健行业。本文综述了呼气VOC生物标志物在筛选各种疾病中的应用,特别强调肝脏疾病和头颈癌作为与代谢紊乱相关的疾病和与代谢紊乱无关的疾病的例子。简要描述了用于呼气VOC检测的单传感器和基于传感器阵列的(电子鼻)方法,以及用于模式识别的机器学习技术。
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引用次数: 4
Compact laser spectroscopic sensor head prototype for time-resolved breath oxygen monitoring. 用于时间分辨呼吸氧监测的紧凑型激光光谱传感器头部原型。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-01-30 DOI: 10.1088/1752-7163/acb07a
Link Patrick, Gerard Wysocki

A small and lightweight optical sensor head prototype with a disposable airway adapter for continuous mainstream monitoring of oxygen at high sampling rate is designed and tested on an optical benchtop. In terms of its size and functionality, the sensor head design is similar to current capnography systems from leading medical equipment manufacturers, and it has been designed within constraints of potential applications in direct breath oxygen monitoring that require direct interaction with the gas inside a breathing tube. The measurement precision of 0.1% O2with a 10 ms integration time are well within the performance required for breath O2monitoring applications.

设计了一种小而轻的光学传感器头原型,该原型带有一次性气道适配器,用于在高采样率下连续主流监测氧气。就其尺寸和功能而言,传感器头部的设计类似于目前领先的医疗设备制造商的二氧化碳成像系统,并且它的设计限制了直接呼吸氧气监测的潜在应用,需要与呼吸管内的气体直接相互作用。测量精度为0.1% o2,集成时间为10 ms,完全符合呼吸o2监测应用所需的性能。
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引用次数: 0
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Journal of breath research
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