The era of micro and nano systems in the biomedical area: bridging the research and innovation gap.

The area of Micro and Nano systems (MNS) focuses on heterogeneous integration of technologies (e.g. electronics, mechanics and biotechnology) and implementation of multiple functionalities (e.g. sensing, processing, communication, energy and actuation) into small systems. A significant amount of MNS activities targets development and testing of systems enabling biomedicine and personal health solutions. Convergence of micro-nano-bio and Information & communication technologies is being leading to enabling innovative solutions e.g. for in-vitro testing and in vivo interaction with the human body for early diagnosis and minimally invasive therapy. Of particular interest are smart wearable systems such as smart textiles aiming at the full integration of sensors/actuators, energy sources, processing and communication within the clothes to enable non-invasive personal health, lifestyle, safety and emergency applications. The paper presents on going major R&D activities on micro-nano-bio systems (MNBS) and wearable systems for pHealth under the European Union R&D Programs, Information and Communication Technologies (ICT) priority; it also identifies gaps and discusses key challenges for the future.

Wearable smart systems: from technologies to integrated systems.

Wearable technology and integrated systems, so called Smart Wearable Systems (SWS) have demonstrated during the last 10-15 years significant advances in terms of, miniaturisation, seamless integration, data processing & communication, functionalisation and comfort. This is mainly due to the huge progress in sciences and technologies e.g. biomedical and micro & nano technologies, but also to a strong demand for new applications such as continuous personal health monitoring, healthy lifestyle support, human performance monitoring and support of professionals at risk. Development of wearable systems based of smart textile have, in addition, benefited from the eagerness of textile industry to develop new value-added apparel products like functionalized garments and smart clothing. Research and development in these areas has been strongly promoted worldwide. In Europe the major R&D activities were supported through the Information & Communication Technologies (ICT) priority of the R&D EU programs. The paper presents and discusses the main achievements towards integrated systems as well as future challenges to be met in order to reach a market with reliable and high value-added products.

Converging micro-nano-bio technologies towards integrated in-vitro testing systems: Current activities and future challenges under the EU-Information & communication technologies program.

Interdisciplinary research towards integrated systems and their applications based on emerging convergence of information & communication technologies, micro-nano and bio technologies is expected to have a direct impact in healthcare, ageing population and well being. Micro-Nano-Bio Systems (MNBS) research and development activities under the European Union's R&D Programs, Information & Communication Technologies priority address miniaturised, smart and integrated systems for in-vitro testing (e.g. lab-on-chips) and systems interacting with the human (e.g. autonomous implants, endoscopic capsules and robotics for minimally invasive surgery). Projects addressing in-vitro testing focus on research, development and testing of technology building blocs (e.g. sample preparation technique, ultra sensitive detection technique, chemistry process for molecular recognition and microfluidics) and their integration into smart and miniaturised systems e.g. DNA & protein arrays, biochips, Lab on Chip and Lab on Card. Current challenges and developed solutions as well as open issues to fully meet technological and socioeconomic needs are presented in this paper as background introductory information to the mini-symposium on "MNBS in-vitro testing". Relevant examples of R&D within the group will be presented in the mini-symposium.

Smart fabrics and interactive textile enabling wearable personal applications: R&D state of the art and future challenges.

Smart fabrics and interactive textiles (SFIT) are fibrous structures that are capable of sensing, actuating, generating/storing power and/or communicating. Research and development towards wearable textile-based personal systems allowing e.g. health monitoring, protection & safety, and healthy lifestyle gained strong interest during the last 10 years. Under the Information and Communication Programme of the European Commission, a cluster of R&D projects dealing with smart fabrics and interactive textile wearable systems regroup activities along two different and complementary approaches i.e. 'application pull' and 'technology push'. This includes projects aiming at personal health management through integration, validation, and use of smart clothing and other networked mobile devices as well as projects targeting the full integration of sensors/actuators, energy sources, processing and communication within the clothes to enable personal applications such as protection/safety, emergency and healthcare. The integration part of the technologies into a real SFIT product is at present stage on the threshold of prototyping and testing. Several issues, technical as well user-centred, societal and business, remain to be solved. The paper presents on going major R&D activities, identifies gaps and discuss key challenges for the future.

Converging micro-nano-bio technologies towards integrated biomedical systems: state of the art and future perspectives under the EU-information & communication technologies program.

Research and development at the convergence of microelectronics, nano-materials, biochemistry, measurement technology and information technology is leading to a new class of biomedical systems and applications e.g. molecular imaging, point of care testing, gene therapy and bionics (including on and inside the body sensors and other miniaturised smart systems) which are expected to revolutionise the healthcare provision and quality of life. In particular they are expected to identify diseases at the earliest possible stage, intervene before symptomatic disease becomes apparent and monitor both the progress of the diseases and the effect of intervention and therapeutic procedures. The group of EC-funded projects on Micro-Nano-Bio Convergence Systems, "so-called" MNBS, is made by projects developing systems that use a vast array of technologies to integrate across traditional boundaries between the micro-nano-bio, and info worlds, enabling a wide range of applications from health care to food quality monitoring. It includes mainly two sub-groups, one dealing with systems for in vitro molecular diagnosis and biological/biochemical analysis and the other is dealing with systems for in vivo interaction with the human body. Current status of development and future challenges, technological and socioeconomic, are briefly presented in this paper as background introductory information to the mini-symposium on MNBS. Relevant examples of R&D within the group will be presented in the mini-symposium.

Wearable health systems: from smart technologies to real applications.

The interest in wearable health systems (WHS) originates initially from the need to extend health services out of the hospital and monitor patients over extensive periods of time. Intelligent WIS are integrated systems in contact with or near the body able to sense, process and communicate biomedical,biochemical and physical parameters - and even carry out actions if necessary. Research and development (R&D) in WHS is mainly driven by two different, but complementary,approaches. The first one is "application-pull", stemming from an increased user demand for new solutions in healthcare. The second one is "technology-push", in which technological innovations lead to new systems and products for healthcare solutions. In both approaches, inter-disciplinarity is a key issue. Synergies across multiple domains like biomedical technologies,micro- and nano-technologies, materials engineering, and Information and Communication Technologies (ICT), enable new approaches to support personal health and well-being. These include, for example, unobtrusive personal health monitoring and point-of-care biochemical testing for disease prevention and early diagnosis, as well as follow-up of treatments. This article presents the state-of-the-art on wearable health systems, outlines current research achievements and indicates research trends and challenges in line with these two approaches.

Wearable health systems and applications: the contribution of information & communication technologies.

The interest for wearable health systems originates mainly from the need to extend health services out of the hospital and monitor patients over extensive periods of time. Smart Wearable Health Systems (SWHS) are integrated systems in contact with or near to the body able to sense, (and/or act), process and communicate biomedical and physical parameters. Significant advances in biomedical technology, materials engineering, micro/nanotechnologies and Information and Communication Technologies (ICT) lead to new possibilities for increasing miniaturisation, communication capabilities and system "intelligence". The new possibilities for wearable monitoring are mainly provided at the level of microsensors, wrist and other body worn devices, and smart biomedical clothing. Research and development in these areas has been strongly supported through public funding and private investments worldwide. In Europe the major R&D activities were promoted and supported by the European Commission, Information Society Technologies (IST) programme, mainly through health telematics (telemedicine, e-Health) and micro-nano technologies activities. The aim of these projects was the development and testing of innovative integrated user-friendly systems, environments and scenarios of use that could lead to market exploitation in a short to mid term future (3-5 years). This paper presents the rationale and the results of research on wearable health systems in Europe and comments on the current challenges and futures perspectives in the field.

Expiratory flow limitation and intrinsic positive end-expiratory pressure at zero positive end-expiratory pressure in patients with adult respiratory distress syndrome.

It has been suggested that in patients with adult respiratory distress syndrome (ARDS), intrinsic positive end-expiratory pressure (PEEPi) is generated by a disproportionate increase in expiratory flow resistance. Using the negative expiratory pressure (NEP) technique, we assessed whether expiratory flow limitation (EFL) and PEEPi were present at zero PEEP in 10 semirecumbent, mechanically ventilated ARDS patients. Because bronchodilators may decrease airway resistance, we also investigated the effect of nebulized salbutamol on EFL, PEEPi, and respiratory mechanics in these patients, and in seven patients we measured the latter variables in the supine position as well. In the semirecumbent position, eight of the 10 ARDS patients exhibited tidal EFL, ranging from 5 to 37% of the control tidal volume (VT), whereas PEEPi was present in all 10 subjects, ranging from 0.4 cm H(2)O to 7.7 cm H(2)O. The onset of EFL was heralded by a distinct inflection point on the expiratory flow-volume curve, which probably reflected small-airway closure. Administration of salbutamol had no statistically significant effect on PEEPi, EFL (as %VT), or respiratory mechanics. EFL (%VT) and PEEPi were significantly higher in the supine position than in the semirecumbent position, whereas the other respiratory variables did not change. Our results suggest that in the absence of externally applied PEEP, most ARDS patients exhibit EFL associated with small-airway closure and a concomitant PEEPi.

Intrinsic positive end-expiratory pressure in mechanically ventilated patients with and without tidal expiratory flow limitation.

OBJECTIVE: To assess static intrinsic positive end-expiratory pressure (PEEPi,st) and expiratory flow limitation (FL) in 32 consecutive mechanically ventilated patients with acute respiratory failure (ARF), using a commercial ventilator with an incorporated device that allows the application of a negative expiratory pressure (NEP). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Thirty-two consecutive ventilated patients with ARF of various etiologies. INTERVENTIONS: Evaluation of respiratory mechanics, PEEPi,st, and FL from pressure, flow, and volume traces provided by the ventilator. MEASUREMENTS: Peak airway pressure, PEEPi,st, dynamic elastance, and interrupter resistance were measured in relaxed patients in a supine position. Comparison of tidal flow-volume curves before and during the application of an NEP of 5 cm H2O was used to assess tidal expiratory FL. RESULTS: Twelve of 32 patients studied exhibited tidal expiratory FL, which was detected by the absence of increase in expiratory flow despite application of an NEP over the entire or part of the baseline expiratory flow-volume curve. All patients exhibited PEEPi,st, which amounted to 1.2 +/- 0.9 cm H2O (mean +/- SD) in the 20 non-FL patients and 7.1 +/- 2.8 cm H2O in the 12 FL patients (p < 0.00001). The majority of patients with ARF resulting from underlying lung disease (11 of 13) had FL and a PEEPi,st > 4 cm H2O, whereas in patients with ARF of extrapulmonary origin, PEEPi,st was always < 4 cm H2O and only one grossly obese patient exhibited FL. Based on multiple regression analysis, in non-FL patients, PEEPi,st correlated significantly only with minute ventilation, whereas in FL patients PEEPi,st correlated significantly with peak airway pressure. CONCLUSIONS: Because all the patients exhibited PEEPi,st and 12 of 32 patients (38%) also had FL, the authors conclude that the assessment of these variables at the bedside could provide useful information concerning respiratory mechanics in mechanically ventilated patients.

Vital signs monitoring from home with open systems.

This study investigates the applicability of a novel codification scheme based on two healthcare informatics standards (namely the VITAL (ENV 13734) and DICOM Sup. 30 Waveform Interchange) in addressing the robust interchange of waveform and medical data in remote healthcare applications. To further address system validation and clinical acceptance issues, pilots were set-up between home-monitoring stations and a hospital-based telemedicine consultation center. The pilots focused in assessing applicability, technical feasibility and performance of the proposed codification scheme based on the two standards. This paper presents the system and services requirements as studied for a home-care application, the design goals for the preservation of security stature, the practical issues of validation and the results of integrating these codification schemes into a commercial patient connected device.

Brain eigenfrequency shifting as a sensitive index of cerebral compliance in an experimental model of epidural hematoma in the rabbit: preliminary study.

OBJECTIVE: To verify brain eigenfrequency shifting after the occurrence of a lesion producing mass effect into the cranial vault. DESIGN: Experimental animal study. SETTING: Laboratory of experimental surgery affiliated with a university critical care department. SUBJECTS: Six adult male New Zealand white rabbits. INTERVENTIONS: A Camino ICP monitor was placed in the parenchyma, and a 5-Fr balloon-tipped catheter and accelerometer were placed into the epidural space. MEASUREMENTS: Before and after the introduction of successive 0.1-mL increments of autologous blood into the balloon, intracranial pressure (ICP) was recorded along with the accelerometer signal obtained during free vibration of the skull triggered by a calibrated hammer. Fast Fourier transformation of the digitized signal provided the eigenfrequency spectrum. The eigenfrequency showing the sharpest decrease after the initial 0.1-mL volume addition was considered as the best frequency, and its variation in response to subsequent 0.1-mL increments represents the brain eigenfrequency shifting. MAIN RESULTS: Brain eigenfrequency shifting to lower values occurs for small blood volume increments (up to 0.2 mL). When volume addition becomes >0.3 mL, brain eigenfrequency shifting to higher values is exhibited. The decrease in best frequency after the initial introduction of 0.1 mL is statistically significant (p = .003), in a range of volume in which no significant intracranial pressure difference appears. The respective variation of ICP is explained using a quadratic curve. For volumes of 0 to 0.1 mL, the change in ICP is not statistically significant (p = .08). CONCLUSIONS: Changes of the brain's physical characteristics by mass addition in the cranial vault can be expressed by brain eigenfrequency shifting. The method seems advantageous because it reliably detects mass additions at low levels where no ICP change occurs. Additionally, it provides serial measurements, and it is less invasive than the currently used methods for intracranial compliance.

A decision support software package for medical treatment of I.C.U. patients.

Critically ill patients admitted in I.C.U. often have multiple complicated problems which necessitate the use of a large number of drugs. The multiple potential interactions between substances and underlying pathologies as well as between substances themselves, obviate the need for a decision support system. We therefore developed a software package for medical treatment support in I.C.U. environment which is based on Microsoft Visual Basic 3.0 and it is organised around the commercially available RDBMS Access 2.0. The database consist of: a) all available substances, b) all generic names of medications available in Greece for each substance, c) incompatibilities (2,300 cases), d) interactions (50,000 cases) and e) cost information for each drug. This system assures the safety of the administered treatment, helps to adjust the dose according to the situation of each patient (anthropometric data, laboratory result, prognostic/severity score e.t.c.) and screens for possible interactions and incompatibilities between the administered drugs. It could also be used for education, treatment algorithms application and it will serve cost-reduction policy. It is a useful and powerful tool for ICU staff which does not impose additional work to the daily practice routine and it is currently under evaluation in clinical settings.

Estimation of frequency-dependent attenuation based on parametric spectral analysis and correlation lags of the demodulated echo signal.

Two new methods for estimating frequency-dependent attenuation are proposed which improve the compromise between the estimation variance of this parameter and the analyzed tissue volume: 1) parametric spectral estimation of the demodulated signal, based on fast Kalman filtering (ARC), 2) implementation of a new mean frequency estimator derived from all the available autocorrelation lags (ACn) of the demodulated signal. Both methods are applied to simulated echo signals. The results are compared to those of other already existing estimators. Both ARC and ACn methods provide equivalent results and a better estimation of attenuation (accuracy ranging from 1.3 to 8%) than the previous methods do (accuracy ranging from 4 to 66%), for analysis windows ranging from 1.5 to 20 microseconds.