Recent advances in breath analysis to track human health by new enrichment technologies

Detection of biomarkers in exhaled breath has been gaining increasing attention as a tool for diagnosis of specific diseases. However, rapid and accurate quantification of biomarkers associated with specific diseases requires the use of analytical methods capable of fast sampling and preconcentration from breath matrix. In this regard, solid phase microextraction and needle trap technology are becoming increasingly popular in the field of breath analysis due to the unique benefits imparted by such methods, such as the integration of sampling, extraction, and preconcentration in a single step. This review discusses recent advances in breath analysis using these sample preparation techniques, providing a summary of recent developments of analytical methods based on breath volatile organic compounds analysis, including the successful identification of various biomarkers related to human diseases.     

Analytical methods for human biomonitoring of pesticides. A review

Biomonitoring of both currently-used and banned-persistent pesticides is a very useful tool for assessing human exposure to these chemicals. In this review, we present current approaches and recent advances in the analytical methods for determining the biomarkers of exposure to pesticides in the most commonly used specimens, such as blood, urine, and breast milk, and in emerging non-invasive matrices such as hair and meconium. We critically discuss the main applications for sample treatment, and the instrumental techniques currently used to determine the most relevant pesticide biomarkers. We finally look at the future trends in this field.     

Liquid-phase microextraction of biomarkers: A review on current methods

The detection and quantification of biomarkers have gained more attention in the medical discipline to evaluating disease progression to manage medical treatment. Biomarkers range from gases to biological macromolecules. Because of the nanomolar range levels of typical biomarkers in plasma, blood, urine, exhalation samples, and other biological fluids as well as complex matrix of biological media, adequate sample preparation methods should be used for quantification of biomarkers. Biomarkers are discussed here generally classified mainly into two subgroups which arisen from disease or exposure compounds. The analytical method is critical for the validity/reliability of a biomarker. Accuracy, precision, reproducibility, recovery, sensitivity, and specificity all have high influence to the consistency with the limit and reference values concerned. In this paper, developments in well-established liquid-phase microextraction techniques for the clinical analysis of biological samples will be reviewed and discussed. This article presents an overview of microextraction methods for biological samples, focusing especially on biomarkers.     

Micellar electrokinetic chromatographic and capillary zone electrophoretic methods for screening urinary biomarkers of human disorders: a critical review of the state-of-the-art

Human urine plays a central role in clinical diagnostic being one of the most-frequently used body fluid for detection of biological markers. Samples from patients with different diseases display patterns of biomarkers that differ significantly from those obtained from healthy subjects. The availability of fast, reproducible, and easy-to-apply analytical techniques that would allow identification of a large number of these analytes is thus highly desiderable since they may provide detailed information about the progression of a pathological process. From among the variety of methods so far applied for the determination of urinary metabolites, capillary electrophoresis, both in the capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) modes, represents a robust and reliable analytical tool widely used in this area. The aim of the present article is to focus the interest of the reader on recent applications of MEKC and CZE in the field of urinary biomarkers and to discuss advantages and/or limitations of each mode.     

醛类标志物的化学衍生化色谱-质谱分析方法进展

人体接触环境中的化学污染物会导致多种疾病,包括癌症、糖尿病、心血管疾病、神经退行性疾病(阿尔茨海默症、帕金森病等)等.作为一类具有高反应活性的亲电化合物,醛类(包括外源性醛类或环境污染物暴露后产生的内源性醛类)可与人体中多种重要生物分子形成共价修饰产物而产生毒害作用.暴露组研究自2005年被首次提出以来一直是一个前沿热...     

生物医学样品中路易氏剂代谢产物分析检测方法研究进展

综述生物医学样品中路易氏剂代谢产物分析方法的研究现状,主要总结了路易氏剂染毒生物医学样品中标志物、样品制备和仪器分析方法的研究进展。路易氏剂染毒生物标志物主要包括游离和加合代谢产物两种,分析过程主要是对选定的生物标志物进行巯基化衍生和富集纯化,之后采用气相色谱–质谱、液相色谱–质谱等仪器对目标物进行检测鉴定。     

CE - a multifunctional application for clinical diagnosis

CE has been used widely as an analytical tool with high separation power taking advantage of size, charge-to-size ratio, or isoelectric point of various analytes. In combination with detection methods, such as UV absorption, electrochemical detection, fluorescence, or mass spectrometry (MS), it allows the separation and detection of inorganic and organic ions, as well as complex compounds, such as polypeptides, nucleic acids, including PCR amplicons from viruses or bacteria. Recent interest in identification of biomarkers of diseases using body fluids leads to development of CE-MS techniques. These applications allowed identification of new potential biomarkers for clinical diagnosis and monitoring of therapeutic interventions. In this report, we present a technical overview of various CE techniques and discuss their applications in clinical medicine.     

Application of NMR metabolomics to search for human disease biomarkers

Since antiquity, humans have used body fluids like saliva, urine and sweat for the diagnosis of diseases. The amount, color and smell of body fluids are still used in many traditional medical practices to evaluate an illness and make a diagnosis. The development and application of analytical methods for the detailed analysis of body fluids has led to the discovery of numerous disease biomarkers. Recently, mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and multivariate statistical techniques have been incorporated into a multidisciplinary approach to profile changes in small molecules associated with the onset and progression of human diseases. The goal of these efforts is to identify metabolites that are uniquely correlated with a specific human disease in order to accurately diagnose and treat the malady. In this review we will discuss recent developments in sample preparation, experimental techniques, the identification and quantification of metabolites, and the chemometric tools used to search for biomarkers of human diseases using NMR.     

Recent Advances of Carbon Nanotubes‐based Electrochemical Immunosensors for the Detection of Protein Cancer Biomarkers

An efficient electrochemical immunosensor can offer the potential for the detection of protein cancer biomarkers due to its high sensitivity, low cost and possible integration in compact analytical devices. In the last several years, researchers have developed various electrochemical immunoassay methods for the detection of protein cancer biomarkers. Significant progresses have been made in the study of electrochemical immunosensor that based on CNTs, especially in the fields of clinical screening and diagnosis of cancer field. This is because CNTs possess unique structural, mechanical and electronic properties that can decrease over‐potential and improve the sensitivity of electrochemical immunosensor. This paper reviews recent advances in the different modified strategies of constructing electrochemical immunosensor based on CNTs for detecting protein cancer biomarkers. CNTs or CNTs hybrid nanomaterials modified electrodes have been firstly introduced as the sensing platforms for the detection of protein cancer biomarkers. On the other hand, CNTs or functional CNTs used as labels in sandwich‐type electrochemical immunosensors have been systematically summarized. These novel strategies and the general principles could increase the sensitivity of the immunosensor, thereby overcoming the limitations of its application in the biosensing field.     

基于分子印迹与表面增强拉曼散射的蛋白质疾病标志物检测研究进展

异常的蛋白质表达与疾病的发生与发展密切相关,因此蛋白质已作为疾病标志物广泛应用于疾病的早期诊断、治疗监测和预后评估.然而,临床样本中的蛋白质疾病标志物通常含量极低,并存在高丰度的基质干扰,对检测方法的特异性和灵敏度提出挑战.目前,蛋白质疾病标志物的检测方法主要是免疫分析.但是,免疫分析主要依赖抗体进行特异性识别,而抗体...     

High‐performance liquid chromatography with diode‐array detection cotinine method adapted for the assessment of tobacco smoke exposure

Smoking is considered to be one of the main risk factors for cancer and other diseases and is the second leading cause of death worldwide. As the anti‐tobacco legislation implemented in Europe has reduced secondhand smoke exposure levels, analytical methods must be adapted to these new levels. Recent research has demonstrated that cotinine is the best overall discriminator when biomarkers are used to determine whether a person has ongoing exposure to tobacco smoke. This work proposes a sensitive, simple and low‐cost method based on solid‐phase extraction and liquid chromatography with diode array detection for the assessment of tobacco smoke exposure by cotinine determination in urine. The analytical procedure is simple and fast (20 min) when compared to other similar methods existing in the literature, and it is cheaper than the mass spectrometry techniques usually used to quantify levels in nonsmokers. We obtained a quantification limit of 12.30 μg/L and a recovery of over 90%. The linearity ranges used were 12–250 and 250–4000 μg/L. The method was successfully used to determine cotinine in urine samples collected from different volunteers and is clearly an alternative routine method that allows active and passive smokers to be distinguished.     

Chromatographic and electrophoretic methods for the analysis of biomarkers of oxidative damage to macromolecules (DNA, lipids, and proteins)

Free radicals and other reactive species can cause oxidative damage to biomolecules when oxidant species exceed the antioxidant defences in the body, resulting in oxidative stress. Oxidatively damaged products have been associated with aging as well as with the development of pathologies like cancer, cardiovascular disease, neurodegenerative disorders, diabetes, inflammation, etc. Reliable measurements of biomarkers of oxidative damage to macromolecules would afford information on the pre-disposition and prognosis of certain pathologies, being of utmost importance in evaluation of the effect of intervention with antioxidants on the incidence of diseases associated to oxidative stress. This review will present and compare different analytical methods, especially those involving chromatographic and electrophoretic techniques, commonly used for the analysis of biomarkers of oxidative damage to the three main macromolecules, namely oxidised DNA, lipid peroxidation products, and protein carbonyls.     

Breath biosensing: using electrochemical enzymatic sensors for detection of biomarkers in human breath

Detection of biomarkers for disease by noninvasive methods is critical for the early diagnosis and screening of disease, enabling prompt treatment. Breath biosensors are a viable option as the exhaled breath contains several biomarkers linked to lung cancer, oxidative stress, diabetes, and other diseases. Breath analysis has been achieved by advanced analytical techniques such as gas chromatography and infrared spectroscopy. However, electrochemical enzymatic breath biosensors offer a cost-effective, sensitive platform for biomarker detection without complex analysis and interpretation by trained laboratory personnel. This review aims to summarize recent advances in the field of electrochemical enzymatic breath biosensors and offer future opportunities from other applications of nonelectrochemical enzymatic breath biosensors.     

电化学生物传感器在污水分析及污水流行病学中的应用进展

近年来,污水流行病学（wastewater-based epidemiology, WBE）已被证明是用来监测社区毒品滥用和公共健康的一种有效评估方法,该方法通过定量分析指定社区污水回收站中污水的药物残留或者代谢物来反推社区中人们对毒品的消耗量并结合指定社区的人口数量对其进行归一化处理. 电化学生物传感器具有响应时间快、成本低、分析样品需求量小、数据分辨率高以及能够现场快速测试等特点,已被广泛应用于疾病快速诊断、环境污染监测、食品安全以及毒品检测等领域. 液相色谱-质谱联用是分析污水中的毒品及其代谢物的主要方法,但随着传感技术尤其是电化学传感器近来的快速发展,也开始被用于研究污水传染病学并可实现现场快速测量. 本文综述了电化学生物传感器在污水中无机污染物（如重金属）、有机污染物（如农药、毒品）、生物分子（如 DNA）以及细菌等微生物分析中的最新进展,同时还论述了目前电化学传感器技术在污水流行病学领域的应用和未来所面临的主要挑战.     

The dual trend in histatins research

We review histatins (Hsts) in order to encourage development of analytical platforms to clarify obscure points in knowledge of this family of antimicrobial and antifungal peptides. To explain the present interest, we outline the number and the nature of Hsts and their known functions (i.e. antimicrobial action, wound closure, biomarkers of stress, satiety, body mass and incipient Alzheimer’s disease, and diagnosis and treatment of addiction, including to cocaine).The two aspects of research on Hsts (i.e. their natural effects on living organisms and their potential use for medical applications, including as biomarkers) make it necessary to develop new analytical methods. The variety of matrices in which Hsts exist (e.g., saliva and tooth-surface-protein pellicle) make it essential to develop new sample-preparation steps and to improve identification and quantitation steps as analytical instrumentation evolves.In this context, metabolomics studies could be of great interest, as contributions of analytical chemists could be one of the keys to achieving the role that they deserve within “-omics” research.     

Potential of label-free detection in high-content-screening applications

The classical approach of high-content screening (HCS) is based on multiplexed, functional cell-based screening and combines several analytical technologies that have been used before separately to achieve a better level of automation (scale-up) and higher throughput. New HCS methods will help to overcome the bottlenecks, e.g. in the present development chain for lead structures for the pharmaceutical industry or during the identification and validation process of new biomarkers. In addition, there is a strong need in analytical and bioanalytical chemistry for functional high-content assays which can be provided by different hyphenated techniques. This review discusses the potential of a label-free optical biosensor based on reflectometric interference spectroscopy (RIfS) as a bridging technology for different HCS approaches. Technical requirements of RIfS are critically assessed by means of selected applications and compared to the performance characteristics of surface plasmon resonance (SPR) which is currently the leading technology in the area of label-free optical biosensors.     

Recent developments in the determination of urinary cancer biomarkers by capillary electrophoresis

Investigation of effective biomarkers for cancers is currently a popular area of study in clinical and cancer researches, because it can potentially lead to pre-cancer screening or pre-cancer diagnosis and may provide useful information on cancer type and the disease's stage of progression. More and more biochemical or chemical fluid components of the human body such as urine, blood, and cerebrospinal fluid have been considered to contain biomarkers, which are useful in cancer researches, pre-cancer diagnosis, and cancer follow-ups during or after cancer treatment. Several modern analytical techniques, such as gas chromatography (GC), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and other separation techniques as well as hyphenated techniques, have been extensively used in study of cancer biomarkers. Among these techniques, CE is considered to be a highly efficient and practical analytical technique because of the small sample volume requirement and its wide separation versatility, ranging from small inorganic molecules to large biomolecules. This review discusses the latest developments involving biomarkers and their analysis by CE, including a discussion of instrumental conditions, method developments, and data analysis.     

The potential of mass spectrometry to study iron-containing proteins used in clinical diagnosis

Many proteins contain iron as metal ion either within their own structures or bound to their active sites. These iron-containing proteins are involved in numerous biological processes and some of them serve as biomarkers of clinical pathologies, not only related to iron homeostasis but also to other physiological disorders. Thus, a variety of analytical strategies have been developed over the last years in order to conduct studies on Fe-containing proteins. Among them, mass spectrometric (MS) methods still remain as preferred tools since they provide the capabilities of structure elucidation together with quantitative possibilities. Therefore, in this work we have tried to summarize the most recent applications of elemental and molecular mass spectrometric-based methods for the characterization (mostly qualitative but quantitative in some cases) of the high abundant Fe-containing proteins used for clinical diagnosis.     

(Xeno)metabolomics for the evaluation of aquatic organism’s exposure to field contaminated water

Environmental (xeno)metabolomics offers a major advantage compared to other approaches for the evaluation of aquatic organism’s exposure to contaminated water because its allows the simultaneous profiling of the xenometabolome (chemical xenobiotics and their metabolites accumulated in an organism exposed to environmental contaminants) and the metabolome (endogenous metabolites whose levels are altered due to an external stressor). This approach has been widely explored in lab exposure experiments, however in field studies environmental (xeno)metabolomics has only started in the last years. In this review, the papers published so far that have performed different (xeno)metabolomics approaches for the evaluation of aquatic organisms exposed to contaminated water are presented, together with their main achievements, current limitations, and future perspectives. The different analytical methods applied including sample pre-treatment (considering matrix type), platforms used (Nuclear Magnetic Resonance (NMR) and low- or high-resolution Mass Spectrometry (MS or HRMS)), and the analytical strategy (target vs non-target analysis) are discussed. The application of (xeno)metabolomics to provide information of xenobiotics mixtures accumulated in exposed organisms, either in lab or field studies, as well as biomarkers of exposure and biomarkers of effect are debated, and finally, the most commonly metabolic pathways disrupted by chemical contamination are highlighted.     

Application of medical and analytical methods in Lyme borreliosis monitoring

Lyme borreliosis (LB) is one of the most common tick-borne diseases in the northern hemisphere. It is a chronic inflammatory disease caused by the spirochaete Borrelia burgdorferi. In its early stages, pathological skin lesions, namely erythema chronicum migrans, appear. The lesions, usually localised at the site of the bite, may become visible from a few weeks up to 3 months after the infection. Predominant clinical symptoms of the disease also involve joint malfunctions and neurological or cardiac disorders. Lyme disease, in all its stages, may be successfully treated with antibiotics. The best results, however, are obtained in its early stages. In order to diagnose the disease, numerous medical or laboratory techniques have been developed. They are applied to confirm the presence of intact spirochaetes or spirochaete components such as DNA or proteins in tick vectors, reservoir hosts or patients. The methods used for the determination of LB biomarkers have also been reviewed. These biomarkers are formed during the lipid peroxidation process. The formation of peroxidation products generated by human organisms is directly associated with oxidative stress. Apart from aldehydes (malondialdehyde and 4-hydroxy-2-nonenal), many other unsaturated components such as isoprostenes and neuroprostane are obtained. The fast determination of these compounds in encephalic fluid, urine or plasma, especially in early stages of the disease, enables its treatment. Various analytical techniques which allow the determination of the aforementioned biomarkers have been reported. These include spectrophotometry as well as liquid and gas chromatography. The analytical procedure also requires the application of a derivatization step by the use of selected reagents.