Photovoltaics, plasmonics, plastic antibodies and electrochromism combined for a novel generation of self-powered and self-signalled electrochemical biomimetic sensors.

This work describes further developments into the self-powered and self-signalled biosensing system that merges photovoltaic cells, plastic antibodies and electrochromic cells into a single target. Herein, the plasmonic effect is introduced to improve the photoanode features of the photovoltaic cell, a dye sensitized solar cell (DSSC), and better electrocatalytic features are introduced in the electrode containing the sensing element. In brief, the DSSC had a counter-electrode of poly(3,4-ethylenedioxythiophene) on an FTO glass modified by a plastic antibody of 3,4-ethylenedioxythiophene and pyrrol. The photoanode had dye sensitized TiO2 modified with gold nanoparticles (AuNPs) to increase the cell efficiency, aiming to improve the sensitivity of the response of hybrid device for the target biomarker. The target biomarker was carcinoembryonic antigen (CEA). The response of the hybrid device evidenced a linear trend from 0.1 ng/mL to 10 µg/mL, with an anionic slope of 0.1431 per decade concentration. The response of the plastic antibody for CEA revealed great selectivity against other tumour markers (CA 15-3 or CA 125). The colour response of the electrochromic cell was also CEA concentration dependent and more sensitive when the hybrid device was set-up with a photoanode with AuNPs. A more intense blue colour was obtained when higher concentrations of CEA were present. Overall, this improved version of the self-powered and self-signalled set-up has zero-requirements and is particularly suitable for point-of-care analysis (POC). It is capable of screening CEA in real samples and differentiating clinical levels of interest. This concept opens new horizons into the current cancer screening approaches.

Microfluidic immunosensor for rapid and highly-sensitive salivary cortisol quantification.

This paper presents a novel poly(dimethylsiloxane) (PDMS) microfluidic immunosensor that integrates a complementary metal-oxide-semiconductor (CMOS) optical detection system for a rapid and highly-sensitive quantification of salivary cortisol. The simple and non-invasive method of saliva sampling provides an interesting alternative to the blood, allowing a fast sampling at short intervals, relevant for many clinical diagnostic applications. The developed approach is based on the covalent immobilization of a coating antibody (Ab), a polyclonal anti-IgG, onto a treated PDMS surface. The coating Ab binds the capture Ab, an IgG specific for cortisol, allowing its correct orientation. Horseradish peroxidase (HRP)-labelled cortisol is added to compete with the cortisol in the sample, for the capture Ab binding sites. The HRP-labelled cortisol, bonded to the capture Ab, is measured through the HRP enzyme and the tetramethylbenzidine (TMB) substrate reaction. The cortisol quantification is performed by colorimetric detection of HRP-labelled cortisol, through optical absorption at 450nm, using a CMOS silicon photodiode as the photodetector. Under the developed optimized conditions presented here, e.g., microfluidic channels geometry, immobilization method and immunoassay conditions, the immunosensor shows a linear range of detection between 0.01-20ng/mL, a limit of detection (LOD) of 18pg/mL and an analysis time of 35min, featuring a great potential for point-of-care applications requiring continuous monitoring of the salivary cortisol levels during a circadian cycle.

Evaluation of the successive approximations method for acoustic streaming numerical simulations.

This work evaluates the successive approximations method commonly used to predict acoustic streaming by comparing it with a direct method. The successive approximations method solves both the acoustic wave propagation and acoustic streaming by solving the first and second order Navier-Stokes equations, ignoring the first order convective effects. This method was applied to acoustic streaming in a 2D domain and the results were compared with results from the direct simulation of the Navier-Stokes equations. The velocity results showed qualitative agreement between both methods, which indicates that the successive approximations method can describe the formation of flows with recirculation. However, a large quantitative deviation was observed between the two methods. Further analysis showed that the successive approximation method solution is sensitive to the initial flow field. The direct method showed that the instantaneous flow field changes significantly due to reflections and wave interference. It was also found that convective effects contribute significantly to the wave propagation pattern. These effects must be taken into account when solving the acoustic streaming problems, since it affects the global flow. By adequately calculating the initial condition for first order step, the acoustic streaming prediction by the successive approximations method can be improved significantly.

Improving acoustic streaming effects in fluidic systems by matching SU-8 and polydimethylsiloxane layers.

This paper reports the use of acoustic waves for promoting and improving streaming in tridimensional polymethylmethacrylate (PMMA) cuvettes of 15mm width×14mm height×2.5mm thickness. The acoustic waves are generated by a 28µm thick poly(vinylidene fluoride) - PVDF - piezoelectric transducer in its ß phase, actuated at its resonance frequency: 40MHz. The acoustic transmission properties of two materials - SU-8 and polydimethylsiloxane (PDMS) - were numerically compared. It was concluded that PDMS inhibits, while SU-8 allows, the transmission of the acoustic waves to the propagation medium. Therefore, by simulating the acoustic transmission properties of different materials, it is possible to preview the acoustic behavior in the fluidic system, which allows the optimization of the best layout design, saving costs and time. This work also presents a comparison between numerical and experimental results of acoustic streaming obtained with that ß-PVDF transducer in the movement and in the formation of fluid recirculation in tridimensional closed domains. Differences between the numerical and experimental results are credited to the high sensitivity of acoustic streaming to the experimental conditions and to limitations of the numerical method. The reported study contributes for the improvement of simulation models that can be extremely useful for predicting the acoustic effects of new materials in fluidic devices, as well as for optimizing the transducers and matching layers positioning in a fluidic structure.

Hemodynamic and respiratory factors that influence the opening of patent foramen ovale in mechanically ventilated patients.

BACKGROUND: Patent foramen ovale (PFO) is an anatomic variant that may lead to several pathological conditions, notably right to left shunt, paradoxical embolism, hypoxemia, and cerebral fat embolism. Mechanical positive pressure ventilation may increase the prevalence of PFO opening in Intensive Care Unit (ICU) patients; however, the respiratory and hemodynamic determinants of PFO opening have been poorly investigated. Contrast-enhanced transesophageal echocardiogram (ce-TEE) is considered the gold standard for PFO detection. We prospectively performed a multicenter study using ce-TEE in order to determine the respiratory and hemodynamic factors that may lead to PFO opening. METHODS: One hundred and eight consecutive ICU adult patients under mechanical ventilation from three tertiary care hospitals, were included in the study. A standard multiplane ce-TEE was performed, and the dimensions and function of the right and left ventricle were studied. In each patient, the right ventricle (RV) end-diastolic area, RV end-systolic area, left ventricle (LV) end-diastolic area, and LV ejection fraction were measured using the modified Simpson's rule and the four-chamber view. At least three bubble tests were performed to detect PFO opening. Ventilatory parameters such as tidal volume, plateau pressure, static lung compliance, and positive end-expiratory pressure were recorded during the bubble test. RESULTS: Data for 81 men and 27 women were analyzed. PFO was detected in 27 % of the study population. Statistical significance was found between the presence of PFO and plateau pressure (odds ratio 3.421, 95 % CI: 1.2-9.4, p =0.017). Additionally, the presence of right ventricular dilatation (RV>LV) was strongly associated with PFO opening (odds ratio 3.163, 95 % CI: 1.2-8.075, p =0.018). CONCLUSIONS: In this group of mechanically ventilated, critically ill adult patients, right ventricular dilatation and plateau pressure above 26 mmHg were significantly associated with foramen ovale opening. Hippokratia 2016, 20(3): 209-213.

Design and fabrication of SiO2/TiO2 and MgO/TiO2 based high selective optical filters for diffuse reflectance and fluorescence signals extraction.

This paper presents the design, optimization and fabrication of 16 MgO/TiO2 and SiO2/TiO2 based high selective narrow bandpass optical filters. Their performance to extract diffuse reflectance and fluorescence signals from gastrointestinal tissue phantoms was successfully evaluated. The obtained results prove their feasibility to correctly extract those spectroscopic signals, through a Spearman's rank correlation test (Spearman's correlation coefficient higher than 0.981) performed between the original spectra and the ones obtained using those 16 fabricated optical filters. These results are an important step for the implementation of a miniaturized, low-cost and minimal invasive microsystem that could help in the detection of gastrointestinal dysplasia.

Measurement of ultrasonic diaphragmatic motion.

The motion characteristics of the diaphragmatic muscle may provide useful information about normal and abnormal diaphragmatic function and indicate diaphragmatic weakness. The objective of this paper was to introduce a simple system for the quantitative analysis of ultrasonic diaphragmatic motion. The measurements routinely carried out by the experts were computed and these include: (i) excursion, (ii) inspiration time (Tinsp) and (iii) cycle duration (Ttot). The system was evaluated on four simulated videos and one real video. Manual and automated measurements were very close. Further work in a larger number of videos is needed for validating the proposed method.

Development of an automatic electronic system to human blood typing.

Blood typing has a vital contribution to the success of life-saving procedures, such as blood transfusions, and it can be critical, especially in emergency situations. For that, in this paper the main principles to the development of a miniaturized, low cost, portable and automatic system to human blood typing, in emergency situations, are presented. In a previous study, the authors validated a general experimental protocol to be applied in the automatic system. Now, the implementation of a specific light source system by using standard Light Emission Diodes (LEDs) was studied. Moreover, the specification of all electronic components to be used in the prototype device was performed.

Spectroscopic detection of gastrointestinal dysplasia using optical microsensors.

The detection of dysplasia in the gastrointestinal tract can be performed using optical microsensors based on thin-film optical filters and silicon photodiodes. This paper describes two optical microsensors that can be used for spectroscopy data collection in two different spectral bands (one in the violet/blue region and the other in the green region) for which two optical filters were designed and fabricated. An empirical analysis of gastrointestinal spectroscopic data using these specific spectral bands is performed. The obtained results show that it is possible to accurately differentiate dysplastic lesions from normal tissue, with a sensitivity and specificity of 77.8% and 97.6%, respectively. Therefore, the developed filters can be used as a tool to aid in diagnosis. The small size of the optical microsensors can enable, in the future, integration in endoscopic capsules.

Fluorescence and diffuse reflectance spectroscopy for early cancer detection using a new strategy towards the development of a miniaturized system.

This paper describes the design of a miniature, cost-effective spectroscopy system for assessing tissue biochemical and morphological information using a few wavelengths. This instrument will integrate thin-film optical filters and silicon photodiodes, avoiding the use of a spectrograph and optical fibers. The components in the set-up design are described. The feasibility of using only 16 wavelengths to accurately extract tissue properties is confirmed on physical tissue models. Also, the suitable spectral performance of several optical filters for the selection of these wavelengths is demonstrated. The reduced size of this device will make possible its implementation in an endoscopic capsule.

Design and fabrication of piezoelectric microactuators based on ß-poly (vinylidene fluoride) films for microfluidic applications.

This paper reports a fabrication method for producing piezoelectric poly (vinylidene fluoride) films in their electroactive ß-phase that features controlled thickness, smooth and flat surface, and high transparency. These piezoelectric films are suitable for being used as integrated microactuators, such as piezoelectric pumps and/or mixers, in microfluidic applications. Their actuation circuit design is also reported. ATR-FTIR, UV-VIS transmittance spectroscopy and SEM techniques were used for calculating the ß-phase content, for determining the transparency and for evaluating the morphology of the produced ß-PVDF films, respectively. ß-PVDF films with a thickness of about 25 µm were deposited by spin-coating. It was concluded that the processing parameter that mostly affect the films quality was their drying temperature. Indeed, the drying temperature of 30 °C proved to be the most suitable for obtaining non-porous and transparent films, with a ß-phase content of approximately 75%.

Lab-on-a-chip with beta-poly(vinylidene fluoride) based acoustic microagitation.

This paper reports a fully integrated disposable lab-on-a-chip with acoustic microagitation based on a piezoelectric ss-poly(vinylidene fluoride) (ss-PVDF) polymer. The device can be used for the measurement, by optical absorption spectroscopy, of biochemical parameters in physiological fluids. It comprises two dies: the fluidic die that contains the reaction chambers fabricated in SU-8 and the ss-PVDF polymer deposited underneath them; and the detection die that contains the photodetectors, its readout electronics, and the piezoelectric actuation electronics, all fabricated in a CMOS microelectronic process. The microagitation technique improves mixing and shortens reaction time. Further, it generates heating, which also improves the reaction time of the fluids. In this paper, the efficiency of the microagitation system is evaluated as a function of the amplitude and the frequency of the signal actuation. The relative contribution of the generated heating is also discussed. The system is tested for the measurement of the uric acid concentration in urine.

Improving alternate flow mixing by obstacles located along a micro-channel.

An essential requirement for any practical fully integrated lab-on-a-chip device is the ability to mix two or more fluids thoroughly and efficiently, i.e., in a reasonable amount of time. This paper presents a way to improve mixing in microfluidic systems combining alternate flows with obstacles using passive mixers. Numerical simulations show that the layers of high and low solute concentration, created by the alternate flow, are split into smaller chunks of fluid, due to the obstacles inserted in the mixing channel, increasing the contact area between high and low concentration regions and decreasing the critical mixing length. This improvement can lead to shorter mixing channels and to low-cost mixers fabricated by planar lithographic technology.

Biological microdevice with fluidic acoustic streaming for measuring uric acid in human saliva.

The healthcare system requires new devices for a rapid monitoring of a patient in order to improve the diagnosis and treatment of various diseases. Accordingly, new biomedical devices are being developed. In this paper, a fully-integrated biological microdevice for uric acid analysis in human saliva is presented. It is based on optical spectrophotometric measurements and incorporates a mixture system based on acoustic streaming, that enhances the fluids reaction due to both heating and agitation generated by this effect. Acoustic streaming is provided by a piezoelectric beta-PVDF film deposited underneath the microfluidic die of the device. Further, it incorporates the electronics for the detection, readout, data processing and signal actuation. Experimental results proved that acoustic streaming based on this piezoelectric polymer is advantageous and reduces in 55% the time required to obtain the analysis results.

A lab-on-a-chip for spectrophotometric analysis of biological fluids.

This paper reports a lab-on-a-chip for application in clinical analysis, especially in the spectrophotometric analysis of biological fluids. It is composed of three parts: (1) a microfluidic system die containing the microchannels fabricated using SU-8 techniques; (2) an optical filtering system based on highly selective Fabry-Perot optical resonators using a stack of CMOS process compatible thin-film layers; (3) a detection and readout system fabricated in a CMOS microelectronic process. The system enables low-cost and selective measurement of the concentration of several biomolecules in biological fluids. Operation is based on optical absorption in a well-defined part of the visible spectrum, defined by the reaction of a specific reagent with a specific biomolecule. Signals proportional to the intensity of the light transmitted through the biological fluid are available at the output in the form of bit streams, which allows simple computer interfacing. Moreover, the optical filtering system enables the measurement using white light illumination, thus avoiding the use of a wavelength dependent light source. This characteristic makes the lab-on-a-chip portable and ensures that the analysis can be performed at any location with instantaneous results, without the use of complex and expensive analysis systems. The quantitative measurement of uric acid and total protein in urine is demonstrated.