Emotion-on-a-chip (EOC): Evolution of biochip technology to measure human emotion using body fluids

Recent developments in nano/micro technology have made it possible to construct small-scale sensing chips for the analysis of biological markers such as nucleic acids, proteins, small molecules, and cells. Although biochip technology for the diagnosis of severe physiological diseases (e.g., cancer, diabetes, and cardiovascular disease) has been extensively studied, biochips for the monitoring of human emotions such as stress, fear, depression, and sorrow have not yet been introduced, and the development of such a biochip is in its infancy. Emotion science (or affective engineering) is a rapidly expanding engineering/scientific discipline that has a major impact on human society. The growing interest in the integration of emotion science and engineering is a result of the recent trend of merging various academic fields. In this paper we discuss the potential importance of biochip technology in which human emotion can be precisely measured in real time using body fluids such as blood, saliva, urine, or sweat. We call these biochips emotion-on-a-chip (EOC). The EOC system consists of four parts: (1) collection of body fluids, (2) separation of emotional markers, (3) detection of optical or electrical signals, and (4) display of results. These techniques provide new opportunities to precisely investigate human emotion. Future developments in EOC techniques will combine social and natural sciences to expand their scope of study.     

生物芯片——二十一世纪革命性的技术

１生物芯片技术的发展 九十年代以来以ＤＮＡ芯片为代表的生物芯片（ｂｉｏｃｈｉｐ）技术［１，２］得到了迅猛发展，目前已有多种芯片出现，以 ＤＮＡ芯片和 ＰＣＲ、毛细管电泳及介电电泳等芯片为代表。在 １９９０年开始实施的人类基因组计划的推动下，生物芯片的一大种类一ＤＮＡ芯片技术得以迅速发展。而且，这些芯片中有的已经在生命科学研究中开始发挥重要作用。生物芯片技术的发展有赖于分子生物学及微加工两方面技术的进步和发展，它将生命科学中许多不连续的过程如样品制备、化学反应和检测等步骤在微小的芯片上实现并使其连续化…     

Biological Microchip for Simultaneous Quantitative Immunoassay of Tumor Markers in Human Serum

The biochip was constructed for simultaneous assay of total and free prostate-specific antigen, α-fetoprotein, cancer embryonic antigen, human chorionic gonadotropin, and neuron-specific enolase. These biochips represent an array of gel elements with covalently immobilized proteins. The major analytic characteristics of the developed method were obtained. It was shown that the results of simultaneous assay of six tumor markers in blood serum well correlated with routine measurements of each marker using enzyme immunoassay kits. This approach allowed us to reveal the hook effect of high concentrations during biochip assay, which prevents distortion of the diagnostic picture at high concentration of the analyte in the sample.     

The cell engineering construction and function evaluation of multi-layer biochip dialyzer

We report the fabrication and function evaluation of multi-layer biochip dialyzer. Such device may potentially be applied to the wearable hemodialysis systems. By merging the advantages of microfluidic chip technology with cell engineering, both functions of glomerular filtration and renal tubule physiological activity are integrated in the same device. This device is designed into a laminated structure, in which the chip number of the superimposed layer can be arbitrarily tailored in accordance with the requirements of dialysis capacity. We propose that such structure can overcome the obstacles of large size and detached structure of the traditional hollow fiber dialyzer. To construct this multilayer biochips dialyzer, two types of dialyzer device with two-layered and six-layered chips are assembled, respectively. Cell adhesion and proliferation on three different dialysis membrane materials under static and dynamic conditions are investigated and compared. The filtration capability, re-absorption function and excrete ammonia function of the resulting multi-layer biochip dialyzer are evaluated. The results reveal that the constructed device can perform higher filtration efficiency and also play a role of renal tubule. This methodology may be useful in developing “scaling down” artificial kidneys that can act as wearable or even implantable hemodialysis systems.     

运用蛋白质芯片技术鉴定干扰素的亚型

目的：采用自制的6株干扰素单克隆抗体，在本实验室建立的金基底蛋白质芯片平台上对IFN-α1b、IFN-α2a、IFN-α2b、IFN-β及IFN-γ进行鉴定。方法：金基底蛋白质芯片用已知亚型的IFN半成品包被，封闭后与自制的6株干扰素单抗反应，再与Cy3-羊抗鼠IgG反应，反应后GenePix4100A芯片扫描仪扫描读数，将结果与ELISA法、Western blot法比较。同样方法检测IFN成品。结果：金基底蛋白质芯片检测技术结果表明，该平台鉴定干扰素的亚型具有特异性，与ELISA法、Western blot法能得出一致的结论。结论：运用本实验室建立的蛋白质芯片平台可以对干扰素的亚型进行鉴定，具有高通量，操作简单，样品用量少，重复性强等优点。     

High efficiency light-induced dielectrophoresis biochip prepared using CVD techniques

This article describes a high-efficiency light-induced dielectrophoresis biochip containing a thin film prepared through inductively coupled plasma chemical vapor deposition (ICPCVD). The biochip comprises two ITO glass substrates and a photoconductive amorphous silicon thin film. The biochip can effectively sort particular particles (or cells) by projecting visible light onto the surface of the silicon thin film. The sorting efficiency of biochips is highly associated with the quality of the deposited amorphous silicon thin films; therefore, the choice of deposition technique is extremely critical. However, no study has examined this problem. Hence, the current study thoroughly compared the efficiency of the biochip when films produced through plasma-enhanced chemical vapor deposition and ICPCVD are used.     

Les puces à oligosaccharides

Saccharides are involved in numerous physiological biological and pathological mechanisms. Understanding the whole saccharides/proteins interactions, saccharides/saccharides and saccharides/DNA (named glycomic) is a key step for both fundamental research and for the development of new therapeutics. Advances in glycobiology have suffered from the large diversity of sugar chains and there are so few amounts available. Taking advantage of the overall progress in DNA biochips technology, oligosaccharide biochips are powerful tools for high-throughput screening.     

Digital imaging scanning system and biomedical applications for biochips

Biochips have been an advanced technology for biomedical applications since the end of the 20th century. Optical detection systems have been a very important tool in biochip analysis. Microscopes are often inadequate for high resolution and big view-area detection of microarray chips, thus some new optical instruments are required. In this work, a novel digital imaging scanning system with dark-field irradiation is developed for some biomedical applications for microarray chips, characterized by analyzing genes and proteins of clinical samples with high specific, parallel, and nanoliter samples. The novel optical system has a high numerical aperture (NA=0.72), a long working distance (wd>3.0 mm), an excellent contrast and signal-to-noise ratio, a high resolving power close to 3 mum, and an efficiency of collected fluorescence more than two-fold better than that of other commercial confocal biochip scanners. An edge overlap algorithm is proposed for the image restructure of free area detection and correcting scanning position errors to a precision of 1 pixel. A novel algorithm is explored for recognizing the target from the scanning images conveniently, removing noise, and producing the signal matrix of biochip analysis. The digital imaging scanning system is equally as good for the detection of enclosed biochips as it is for the detection of biological samples on a slide surface covered with a glass cover slip or in culture solution. The clinical bacteria identification and serum antibody detection of biochips are described.     

生物芯片技术在生命科学基础研究中的作用

所谓生物芯片（Ｂｉｏｃｈｉｐ）即应用于生命科学和医学领域中作用类似于电子芯片的器件。它可以对生物分子进行快速并行处理，把生命科学中许多不连续的过程如样品制备、化学反应和结果检测等步骤移植到芯片上并使其连续化和微型化。其突出特点是信息量大，处理速度快。正是由于这些特点，使得生物芯片有着非常广阔的应用前景。它的应用范围涉及生命科学基础研究、疾病诊断和治疗、药物筛选和新药开发、食品卫生监督、司法鉴定、国防、航天航空等领域。生物芯片作为一种操作平台，人们利用它可以开展许多工作，这和计算机中的Ｗｉｎｄｏｗ…     

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

Although several drugs are available to treat recurrences of human epithelial ovarian cancer (EOC), clinical responses often remain short lived and lead to only marginal improvements in patients' survival. One of the new drugs proposed for recurrent platinum‐resistant EOC patients is trabectedin (Trab), a marine‐derived antitumor agent initially isolated from the tunicate Ecteinascidia turbinata and currently produced synthetically. Predictive biomarkers of therapy response to this drug and the potential use of non‐invasive functional MRI and MRS approaches for an early assessment of Trab efficacy have not yet been evaluated, although they might be relevant for improving the clinical management of EOC patients. In the present work we combined functional and spectroscopic magnetic resonance technologies, such as in vivo diffusion‐weighted MRI and ¹H MRS, with ex vivo high resolution MRS (HR‐MRS) metabolomic analyses, with the aim of identifying new pharmacodynamic markers of Trab effectiveness on well characterized, highly aggressive human SKOV3.ip (a HER2‐enriched cell variant derived from SKOV3 cells) EOC xenografts. In vivo treatment with Trab (three consecutive weekly 0.2 mg/kg i.v. injections) resulted in the following: (1) a significant reduction of in vivo tumor growth, along with the formation in cancer lesions of diffuse hyper‐intense areas detected by T₂‐weighted MRI and attributed to necrosis, in agreement with histopathology findings; (2) significant increases in the apparent diffusion coefficient mean and median values versus saline‐treated control tumors; and (3) a significant reduction in the choline‐containing metabolites' signal detected by quantitative in vivo MRS. Multivariate and quantitative HR‐MRS analyses on ex vivo tissue samples revealed Trab‐induced alterations in phospholipid and glucose metabolism identified as a decrease in phosphocholine and an increase in lactate. Collectively, these data identify Trab‐induced functional MRI and MRS alterations in EOC models as a possible basis for further developments of these non‐invasive imaging methods to improve the clinical management of EOC patients.     

The Pursuit of ES Cell Lines of Domesticated Ungulates

In contrast to differentiated cells, embryonic stem cells (ESC) maintain an undifferentiated state, have the ability to self-renew, and exhibit pluripotency, i.e., they can give rise to most if not all somatic cell types and to the germ cells, egg and sperm. These characteristics make ES cell lines important resources for the advancement of human regenerative medicine, and, if established for domesticated ungulates, would help make possible the improvement of farm animals through their contribution to genetic engineering technology. Combining other genetic engineering technologies, such as somatic cell nuclear transfer with ESC technology may result in synergistic gains in the ability to precisely make and study genetic alterations in mammals. Unfortunately, despite significant advances in our understanding of human and mouse ESC, the derivation of ES cell lines from ungulate species has been unsuccessful. This may result from a lack of understanding of species-specific mechanisms that promote or influence cell pluripotency. Thorough molecular characterizations, including the elucidation of stem cell “marker” signaling cascade hierarchy, species-appropriate pluripotency markers, and pluripotency-associated chromatin alterations in the genomes of ungulate species, should improve the chances of developing efficient, reproducible technologies for the establishment of ES cell lines of economically important species like the pig, cow, goat, sheep and horse. Mention of a trade name, proprietary product or vendor does not constitute a guarantee or warranty of the product by USDA or imply its approval to the exclusion of other suitable products or vendors.     

Biochip array-based analysis of plasma cytokines in HIV patients with immunological and virological discordance

Assessment of cytokines in body fluids or cells provides important information in understanding the disease process and designing treatment strategies. Recent introduction of antibody-based protein arrays have provided investigators simultaneous and specific detection of multiple analytes in a single sample using minimum volumes. In this study, we used a biochip array system capable of measuring 12 cytokines and growth factors (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1alpha, IL-1beta, IFN-gamma, TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF)) in HIV patients with immunological and virological discordance (discordant) to find out differences if any, in their plasma cytokine profiles when compared with concordant HIV-infected individuals. A sandwich chemiluminescent assay was performed with plasma specimens of 110 HIV patients (55 discordant, 55 concordant) and 22 normal healthy individuals followed by enzyme-linked immunosorbent assay (ELISA) to the confirm levels of cytokines and growth factors that showed significant differences in the two groups. The discordant HIV patients showed significantly higher levels of plasma VEGF (P = 0.001) and EGF (P = 0.034) levels when compared with concordant patients. Overall, the patients showed significantly higher levels of TNF-alpha, MCP-1 and VEGF when compared with the normal healthy controls (P < 0.05). ELISA for VEGF (P < 0.001) and EGF (P = 0.004) confirmed the comparison obtained with biochip array, between the discordant and concordant patients. The results of cytokine quantitation by biochip array and ELISA confirmed that this technology is not only comparable but also has a good potential in the future applications involving measurement of multiple cytokines with limiting specimens.     

Towards portable, real-time, integrated fluorescence microarray diagnostics tools

We present recent results on biochips slides with high fluorescence efficiency and their associated readout systems. To obtain the full performance made possible by such slides, the chemical surface functionalization has to be improved, as formerly unobservable defects of the functionalization are now made observable through the improved efficiency. The systems are based on the integration of the hybridization and readout functions into a single machine instead the usual two separate systems, quite cumbersome and expensive. Ultimate performance is reached with systems using standard imaging circuits, CCD or CMOS, as the biochip substrate. In this case, one can obtain a remarkable miniaturization of the full optical system and the integrated hybridization chamber/readout head can be reduced to the size of a webcam.     

The relevance of the transfer of molecular information between natural and synthetic materials in the realisation of biomedical devices with enhanced properties

Past and recent attempts to introduce in synthetic polymers molecular information from natural substances through simple blending, template polymerization and molecular imprinting are reviewed. The most promising approaches that can open the way to the realisation of new materials with improved biocompatibility, antibody- or enzyme-like performances are analysed more deeply. The realisation of bioartificial blends from natural and synthetic polymers, molecularly imprinted nanospheres or membranes that can act as recognition element in (bio)sensing devices, as synthetic enzymes or as key constituents of body fluids purification tools is presented in order to make the reader aware of the fascinating possibilities that these techniques make available to the biomedical science and engineering in the close future. The last part of the paper describes recent attempts to insert recognition elements for large molecules as proteins, DNA segments, viruses or whole cells in synthetic polymer systems, in order to develop new systems in the treatments of diseases and for tissue-engineering applications.     

人体运动分析的发展与应用回顾

运动分析是研究人体运动的一门学问。通过对运动过程的分析和研究,可以简化运动过程,方便运动标准化、提高运动效率。目前运动分析技术已广泛应用在医疗、运动科学、康复、娱乐等领域。从临床来说,运动分析己被运用于各种神经骨骼肌肉系统相关的疾病诊断、个性化治疗规划,也是评估治疗效果与医疗器材,包括骨科植入物、矫辅具以及康复器材的重要客观科学工具。未来运动分析方法的进步,将同时带动骨科、康复科、精准个体化医疗和医学工程等领域的进步。本文从骨科生物力学的角度,介绍运动分析的发展简史、现代常见的运动捕捉技术与设备、运动分析的临床应用与限制以及未来运动分析可能的发展方向。     

The development of a closed-loop controlled functional electrical stimulation (FES) in gait training

Introduction

The last couple of decades have witnessed a rapid development of control and systems theory. Parallel to these developments, advances in electronics and especially computers have resulted in many application areas of control theory, hitherto making do with their own methodologies, being strongly influenced by these developments, and thus adopting their methods. Clinical medicine, although basically a science apparently unrelated to control engineering, is being affected to such an extent that it is now possible to use available online control devices, especially during surgical operations and in intensive care units. This, on the other hand, is hardly surprising if one considers all the other application areas of control engineering, like mining, hazardous industry, air travel or nuclear power production, which have resulted in increased safety standards where human. lives are concerned.     

Polyamines as cancer markers: applicable separation methods

Spermine, spermidine, putrescine and cadaverine are aliphatic amines widely spread in the human body. Their concentrations together with their acetyl conjugates increase significantly in the biological fluids and the affected tissues of cancer patients. Their concentrations decrease with the improvement in the patient's condition on multiple therapy. Various chromatographic techniques are frequently used in monitoring concentrations of di- and polyamines in cancer. Among these techniques, thin-layer chromatography and liquid chromatography using pre- or postcolumn derivatization, separating on a reversed-phase or an ion-exchange column are the most commonly used. Besides, high-resolution capillary column gas chromatography (GC) is increasingly used over packed column GC, and in recent years, capillary zone electrophoresis has also gained some importance in polyamine determinations. The review examines the prospects and the limitations of polyamines as cancer markers using chromatographic and electrophoretic techniques.     

生物芯片技术与基础医学研究

典型的生化分析系统通常包括三个部分：样品制备、生化反应和结果检测。许多年来,如何使这三个部分成为有机的结合体一直是许多科学工作者和企业界人上的梦想。生物芯片——分子生物学和半导体工业的完美结合——使得这一梦想成为了现实。生物芯片是应用于生命科学和医学领域中作用类似于电子芯片的器件,是便携式生物化学分析器的核心技术。通过对微加工获得的微米结构做生物化学处理能使成千上万个与生命相关的信息集成在一块厘米见方的芯片上。生物芯片将生命科学中许多不连续的过程如样品制备、化学反应和结果检测步骤移植到芯片上并使…     

Non-invasive quantification of organ damage

Quantitative evaluation of organ damage can be achieved by non-invasive, direct or indirect methods. Direct methods include echography, tomography, scintigraphy and magnetic resonance. The accuracy of these imaging techniques has been demonstrated in human medicine. Most of them have not been validated in animals, however, and their use is limited by cost. Indirect methods are based on determination of the total release of intracellular markers (mainly enzymes) into body fluids. Quantification of organ damage depends on extracellular disposition of the marker. Thus, in the kidney, the marker is directly and totally leaked into the urine and is voided at each micturition. The amount of marker eliminated in this way allows easy quantification of organ damage occurring during the period preceding the micturition.Muscle markers with molecular weights exceeding 50 kDa reach the blood via the lymph. This results in (a) partial inactivation, (b) delay between cell damage and increased plasma concentration and (c) accumulation in the plasma as long as delivery into the plasma exceeds clearance. In such cases, quantitative evaluation requires pharmacokinetic tools and calculation of the area under the curve (concentration vs time) and of the plasma clearance. Comparison of the intensity and chronology of markers located in different cell compartments may contribute to the understanding of pathophysiological events.Originally presented at ECCP 95.     

Topographic approach to the study of the human body

Recent developments in medical imaging techniques such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) have been explosive. These modalities provide 3D information about the human body and assess tissue damage in various pathological conditions. To complement the diagnostic usefulness of these imaging techniques, we have designed a system of topographic coordinates based on the principles of global projection cartography in which lines of latitude and longitudes are assigned to the surface of the human body. We designated the median sagittal plane as corresponding to the Greenwich Meridian (zero longitude) in global cartography. From the median sagittal plane (M0), vertical lines of longitude or "great circles" divide the body into 12 zones that are 30 degrees apart. Parallel lines of latitude are assigned according to surface anatomy landmarks. Studying the 3D reconstruction of anatomical structures is important for: 1) devising a system of coordinates; 2) allowing biomedical measurements to be made; and 3) drawing maps that may be useful in some clinical procedures (e.g., biopsies).