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This paper reports on the development of a fluorescent label-free aptamer assay integrated in a lab-on-chip (LoC) system for the detection of Ochratoxin A (OTA). The detection system relies on the integration, on a single glass substrate, of an array of amorphous silicon photosensors and a long pass interferential filter. The aptamer assay, integrated into the microfluidic network, is an aptasensor having affinity versus OTA, selected as a case study. The fluorescent molecule is a "light switch" complex [Ru(phen)

This work reports on the development of a large-area thin film heater for lab-on chip applications. The device is a chromium/aluminum/chromium stacked structure with a spiral shape fabricated on a $5\times 5\text{cm}^{2}$ glass substrate through microelectronic technologies. Its geometry has been designed and optimized by COMSOL Multiphysics in terms of pitch and line width to achieve a uniform temperature distribution. Measurements performed with a thermo-camera show temperature variation below 1.5°C over 5cm2 area in excellent agreement with numerical modeling. To our knowledge, this is the largest area with such temperature uniformity achieved with a single heater in lab-on-chip systems. This opens the route for large-area thermal treatments as multiple-well DNA amplification or cell culture.

Highlights • An adequate Physical Activity level can help patients to maintain good glycemia control. • People with type 1 diabetes reduced their Physical Activity level during quarantine. • People with type 1 diabetes increased mean glycemic values. • Specific suggestions on home training manage should be given to people with type 1 diabetes., Aims Coronavirus disease (Covid-19) could lead persons with pre-existing medical conditions to severe respiratory infections. The Italian Government introduced quarantine to limit viral transmission. This measure could lead people with type 1 diabetes (PWT1D) to disrupt daily care routine including PA practice with difficulties in glycemia management. This study aims to explore PA level in PWT1D before and during quarantine and to describe variation in glycemia values. Methods An online survey investigating medical factors and the perceived and PA level in pre-established period before and after the introduction of quarantine was developed. Comparison between pre and post quarantine was assessed by Wilcoxon Signed Ranks test for continuous variables. Results A total of 154 subjects satisfied the eligibility criteria (54.5% males, 44.8±12.5 years). We found a decrease of PA level (Godin Scale Score 25±1.7vs38.6±1.7 points), steps number and minutes of exercise (respectively 12.606±5026vs4.760±3.145 and 66±4vs38±3) and an increase of glycemia values (142.1± 25.4 mg/dLvs150.8±29.4 mg/dL) Conclusions PWT1D reported a decrease in exercise and worst glycemia. Although PWT1D tried to remain active, their PA level was inadequate to prevent glycemia rising. The difficult to maintain a glycemic control could expose patients to diabetes complications and to an higher risk to counteract infections.

Innovative materials for the integration of aptamers in Lab-on-Chip systems are important for the development of miniaturized portable devices in the field of health-care and diagnostics. Herein we highlight a general method to tailor an aptamer sequence in two subunits that are randomly immobilized into a layer of polymer brushes grown on the internal surface of microfluidic channels, optically aligned with an array of amorphous silicon photosensors for the detection of fluorescence. Our approach relies on the use of split aptamer sequences maintaining their binding affinity to the target molecule. After binding the target molecule, the fragments, separately immobilized to the brush layer, form an assembled structure that in presence of a “light switching” complex [Ru(phen)2(dppz)]2+, emit a fluorescent signal detected by the photosensors positioned underneath. The fluorescent intensity is proportional to the concentration of the target molecule. As proof of principle, we selected fragments derived from an aptamer sequence with binding affinity towards ATP. Using this assay, a limit of detection down to 0.9 µM ATP has been achieved. The sensitivity is compared with an assay where the original aptamer sequence is used. The possibility to re-use both the aptamer assays for several times is demonstrated.

Concrete has been one of the most common building materials used in construction in the world for many centuries. The manufacturing of concrete plays an important role in the generation of global warming emissions and waste and causes non-renewable resource depletion. This research assesses the environmental impacts of the use of supplementary cementitious materials (SCMs) and engineered nanomaterials (ENMs) (i.e., by-products) as partial replacement of ordinary Portland cement in concrete. It also evaluates the structural performance of the use of construction and demolition waste as partial replacement of natural aggregate in concrete in terms of compressive strength and durability. Results show that the use of SCMs and ENMs reduces the global warming impact (GWI) and the cumulative energy demand (CED) of concrete production without reducing strength and durability. In some cases, it enhances durability and strength. However, there is a tradeoff between durability and strength improvement with the use of reengineered by-products resulting in increased GWI and CED. Although they produce almost the same GWI and CED as those of OPC concrete, improving the use of recycled aggregates as a partial natural aggregate replacement can reduce the use of virgin materials.

The study and quantification of the effects of the space environment on human body is a primary task for future manned deep space missions. The risk models for radiation exposures incurred by astronauts beyond low-Earth orbit, have different limitations due to the difficulty to have terrestrial parallels on which to base risk estimates. Indeed, no terrestrial sources fully reproduce the deep space energy spectrum and the multi directional flux of the cosmic radiation. In situ analysis would therefore be fundamental in order to enable reliable studies about the effects of the radiation environment on living organisms as well as to evaluate customized radiological countermeasures for astronauts. A micro-incubator suitable for cubesat missions for studying in situ the effects of the space environment on cellular cultures is presented. The device is based on lab-on-chip technology with integrated thin-film sensors and actuators for the active control of the environmental conditions of the cell culture and for the monitoring of its metabolic status. In particular, the device includes an incubation chamber connected to a microfluidic network for the supply of nutrients and/or pharmaceuticals. A second network is used for the distribution of carbon dioxide through a thin gas-permeable membrane. On-chip on-demand production of carbon dioxide can be eventually achieved from the pyrolysis of sodium bicarbonate stored in a separate reservoir with a dedicated thin film heater. The same network can be used to supply a controlled atmosphere from a pressurized tank. The on-chip hydrogenated amorphous silicon photodiodes are used to measure the light emitted by genetically-modified cell cultures that express a bio-luminescent behavior when subjected to given stress conditions. Accurate temperature control is achieved by means of additional on-chip thin-film diodes and a transparent indium-tin-oxide heater located beneath the incubation chamber. From technological point of view, the system relies on the combination of different thin- and thick-film fabrication technologies jointly used with the aim to achieve a compact, automated and low-power device that represents a viable solution for biological experiments aboard cubesat satellites.

This work presents an equivalent electrical circuit of hydrogenated amorphous silicon diodes. It is constituted by four diodes and two resistances. Each element is directly related to the physical behavior of the thin film structure and models the different conduction regimes of the device.Results show a very good fitting of the experimental current-voltage characteristic up to several hundreds of millivolts in both forward and reverse bias conditions and demonstrate the suitability of the developed model for designing the diode fabrication parameters for specific application.

The integration of systems for real-time monitoring of DNA amplification reactions is rather limited, because the heating system, the temperature control and the detection system are usually realized with separate modules. In this work, a lab-on-a-chip system for real-time monitoring of the multiple displacement amplification reaction (MDA) is presented. The amplification and detection unit consists of a system-on-glass (SoG) coupled to a microfluidic chip. The SoG includes thin film metallic resistors and amorphous silicon temperature sensors to control the temperature, as well as amorphous silicon photosensors and an interference filter for fluorescence detection on a single glass plate. The amplification reaction is carried out in the microfluidic chip made of cyclic olefin copolymer (COC). By using this setup, the multiple displacement amplification reaction can be monitored in real-time using the fluorophore [Ru(phen)2(dppz)]2+.

The detection of life markers is a high priority task in the exploration of the Solar System. Biochips performing in-situ multiplex immunoassays are a very promising approach alternative to gas chromatography coupled with mass spectrometry. As part of the PLEIADES project, we present the development of a chemiluminescence-based, highly integrated analytical platform for the detection of biomarkers outside of the Earth. The PLEIADES device goes beyond the current lab-on-chip approaches that still require bulky external instrumentation for their operation. It exploits an autonomous capillary force-driven microfluidic network, an array of thin-film hydrogenated amorphous silicon photosensors, and chemiluminescence bioassays to provide highly sensitive analyte detection in a very simple and compact configuration. Adenosine triphosphate was selected as the target life marker. Three bioassay formats have been developed, namely (a) a bioluminescence assay exploiting a luciferase mutant with enhanced thermal and pH stability and (b and c) binding assays exploiting antibodies or functional nucleic acids (aptamers) as biospecific recognition elements and peroxidase or DNAzymes as chemiluminescence reporters. Preliminary results, showing limits of detection in the nanomolar range, confirm the validity of the proposed approach.

This paper reports the development of a miniaturized lab-on-glass,suitable for the on-chip detection of living cell bioluminescence and their on-chip thermal treatments. The glass substrate hosts, on one side, hydrogenated amorphous silicon diodes, working as both temperature sensors and photosensors, and, on the other side, transparent thin films acting as heating sources. The main challenge of the work is the determination of the correct fabrication recipes in order to satisfy the compatibility of different microelectronic steps. The measured uniformity of temperature distribution, sensitivity of the temperature sensors, reverse dark current and spectral response of the photosensors demonstrate the successful technological integration and the suitability of the developed lab-on-glass to control the cell temperature and detect the BL emission with high sensitivity.

The paper proposes a part of an extended research devoted to the application of Lab-on-Chip systems for the detection of viral infections. The focus is on accurate lumped element modeling, simulation and experimental characterization of the thermal behavior of an integrated glass micro-heater, useful for the design and simulation of dedicated electronic controlling systems. A lumped three-compartment model for the analysis of the thermal behavior of a heater has been proposed and discussed. The mathematical model was extensively simulated, and the associated parameters have been chosen in order to minimize the L2 norm of the error with respect to experimental data collected though an experiment campaign.

This work reports on design and fabrication of a compact lab-on-chip system, based on detection of electrochemiluminescence (ECL) through thin film sensors. The proposed system couples an optoelectronic platform to a disposable microfluidic chip. The optoelectronic platform includes amorphous silicon photosensors for detection of ECL, while the microfluidic chip contains the ECL electrodes and the biological solutions to be analyzed. Optoelectronic characterization of photosensors and preliminary test on the ECL electrodes by cycling voltammetry show the suitability of these devices for the achievement of low-noise and high sensitive system.

Lab-on-chip are analytical systems which, compared to traditional methods, offer significant reduction of sample, reagent, energy consumption and waste production. Within this framework, we report on the development and testing of an optoelectronic platform suitable for the on-chip detection of fluorescent molecules. The platform combines on a single glass substrate hydrogenated amorphous silicon photosensors and a long pass interferential filter. The design of the optoelectronic components has been carried out taking into account the spectral properties of the selected fluorescent molecule. We have chosen the [Ru(phen)2(dppz)]2+ which exhibits a high fluorescence when it is complexed with nucleic acids in double helix. The on-glass optoelectronic platform, coupled with a microfluidic network, has been tested in detection of double-stranded DNA (dsDNA) reaching a detection limit as low as 10 ng/µL.

This work presents the development and testing of an integrated system for on-chip detection of thermochemiluminescent biomolecules. The activation energy of the reaction is provided by a transparent structure of thin film heaters deposited on one side of a glass substrate. Light, passing through the substrate, reaches an array of amorphous silicon differential structure deposited on the opposite side of the glass substrate. The structure is designed to perform differential current measurements between a light- shielded diode, whose current is sensitive only to temperature, and a photosensor, sensitive to both incident light and temperature. The device therefore balances the thermal variations of the photodiode current and reduces the dark-current noise. These features make the presented system very appealing as highly miniaturized micro-analytical devices for biosensing applications.

This article presents the successful design, fabrication and testing of a miniaturized system integrating capillarity and electrowetting-on-dielectric (EWOD) technology in a microfluidic network. In particular, the change in hydrophobicity occurring at the interphase between a capillary channel and a hydrophobic layer has been exploited using EWOD as a stop-go fluid valve. The combination of capillary forces and EWOD technology to control the fluid movement opens the possibility to implement a wide variety of microfluidic configurations to perform different biomedical assays with a low-power consumption process. These assays could be easily and inexpensively integrated in lab-on-chip systems featuring small size and high-throughput characteristics.

This paper presents the development of a compact optoelectronic device suitable for on-chip detection of fluorescent molecules. In order to obtain a highly integrated device, a long-pass multi-dielectric filter has been integrated with thin-film amorphous silicon photosensors on a single glass substrate. Filter rejects the excitation light, allowing the reduction of the distance between the source and the fluorescent site and avoiding the use of external optical component. The compatibility of the technological processes determined the materials and the temporal sequence of the device fabrication. The developed device has been designed for the fluorescence detection of ruthenium complex based molecules and tested, as a proof of concept, for the detection of double-stranded DNA down to 0.5 ng. Results demonstrate the correct operation of the integrated system in both rejecting the excitation light and in detecting the fluorescent signal, demonstrating the suitability of this optoelectronic platform in practical biomedical applications.

In this paper, we present an optoelectronic system-on-glass (SoG), suitable for detection of fluorescent molecule. It integrates, on the same glass substrate, an array of amorphous silicon (a-Si:H) photosensors and a thin film interferential filter. The system can be directly coupled with another glass substrate hosting a polydimethylsiloxane based microfluidic network where the fluorescent phenomena occur. The compatibility of the different technological steps to attain on the same glass substrate the photosensors and the filter determined the sequence, the selection of materials and the deposition parameters of the whole process. The electro-optical characterization of the photodiode, performed after the filter deposition, demonstrated the efficacy of the filter in reducing the excitation light. The system has been successfully tested using the ruthenium complex [Ru(phen)2(dppz)]2+, a fluorescent dye which works as DNA intercalating molecule. © Springer International Publishing AG 2018.

The present paper describes the development of an integrated lab-on-chip, in which viral DNA amplification with real-time on-chip detection is carried out under constant temperature of 65 °C. The lab-on-chip is composed of a disposable 10-μL polydimethylsiloxane reaction chamber which is thermally and optically coupled to a glass substrate that hosts a thin-film metallic resistive heater and thin-film amorphous silicon diodes which act as temperature and radiation sensors. A loop-mediated isothermal amplification (LAMP) technique was optimized to specifically amplify parvovirus B19 DNA and coupled with Bioluminescent Assay in Real Time (BART) technology to provide real-time detection of target DNA. The experimental results demonstrate the ability of the proposed device to discriminate among different concentrations of viral DNA with an excellent agreement with standard off-chip methods.

In this paper we present a compact technological demonstrator including on the same glass substrate an electrowetting-on-dielectrics (EWOD) system, a linear array of amorphous silicon photosensor and a capillary-driven microfluidic channel. The proposed system comprises also a compact modular electronics controlling the digital microfluidics through the USB interface of a computer. The system provides therefore both on-chip detection and microfluidic handling needed for the realization of a ‘true’ Lab-on-Chip. The geometry of the photosensors has been designed to maximize the radiation impinging on the photosensor and to minimize the inter-site crosstalk, while the fabrication process has been optimized taking into account the compatibility of all the technological steps for the fabrication of the EWOD system, the photosensor array and the microfluidics channels. As a proof of the successful integration of the different technological steps we demonstrated the ability of the a-Si:H photosensors to detect the presence of a droplet over an EWOD electrode and the effective coupling between the digital and the continuous microfluidics, that can allow for functionalization, immobilization and recognition of biomolecules without external optical devices or microfluidic interconnections.

This work reports on the design, simulation and fabrication of an autonomous microfluidic network. It is a part of a highly integrated, new analytical platform for the multiparametric detection of bio-organic molecules in extra-terrestrial environment. The proposed microfluidic system, made in SU-8 3050, allows to obtain an autonomous microfluidic network able to have simultaneous capillary filling and fresh solution into each site of detection avoiding cross-contamination among different sites. Computational Fluid Dynamics (CFD) simulations have been carried in order to verify the proper operation of the designed microfluidic network and to optimize it. Technological processes have been refined and adapted in order to ensure good adhesion, using low-temperature and low-pressure bonding avoiding the risk of breaking the glass slides. Experiments have been conducted to verify the autonomous capillary filling of the entire network and its rinsing with buffer solution. The experimental results are in good agreement with the simulations.

In this paper, we present an improved microfluidic network based on polydimethylsiloxane (PDMS) and thin film heaters for thermal treatment of biomolecules in lab-on-chip systems. It relies on the series connection of two thermally actuated valves, at both inlet and outlet of the network, in order to reduce leakage of sample when its process temperature approaches 100 °C. The spatial arrangement of valves and microfluidic channels in between has been optimized using COMSOL Multiphysics, through the investigation of the system thermal behavior. Taking into account the simulation results, the geometries of the heaters have been defined following standard microelectronic technologies and the microfluidic network has been fabricated by soft lithography. The experiments demonstrate that with the proposed configuration the liquid evaporation is strongly reduced since more than 80% of the sample is recovered after a practical thermal treatment experiment.

This work combines a lab-on-chip device with an electronic system for the achievement of a small-scale and low-cost thermal treatment of biomolecules. The lab-on-chip is a 1.2 mm-thick glass substrate hosting thin film resistor acting as heater and, on the other glass side, amorphous silicon diodes acting as temperature sensors. The electronic system controls the lab-on-chip temperature through a Proportional-Integral-Derivative algorithm. In particular, an electronic board infers the temperature measuring the voltage across the amorphous silicon diodes, which are biased with a constant forward current of 50 nA, and drives the heater to achieve the set-point temperature. The characterization of the whole system has been carried out implementing the thermal cycles necessary in the polymerase chain reaction technique for amplification of DNA. To this purpose, the lab-on-chip has been thermally coupled with another glass hosting a microfluidic network made in polydimethilsiloxane, and the time evolution of temperature has been carefully monitored. The measured performances in terms of heating rate, cooling rate and settling time demonstrate that the proposed system completely fulfills the requirements of the investigated biological application.

This work presents a miniaturized lab-on-chip system suitable for monitoring the activity of living cells through the on-chip detection of their bioluminescence emission. The system integrates amorphous silicon diodes, acting as temperature and light sensors, and indium tin oxide film, acting as heater, on a single glass substrate. During its operation, the glass is thermally and optically coupled to the investigated cells and electrically connected to an electronic board, which controls the lab-on-chip temperature and monitors the sensor photocurrents. The proposed lab-on-chip is particularly attractive for the development of portable cell-based biosensors useful for biological activity monitoring as well as for cell cytotoxicity evaluation.

Lab-on-Chip are miniaturized systems able to perform biomolecular analysis in shorter time and with lower reagent consumption than a standard laboratory. Their miniaturization interferes with the multiple functions that the biochemical procedures require. In order to address this issue, our paper presents, for the first time, the integration on a single glass substrate of different thin film technologies in order to develop a multifunctional platform suitable for on-chip thermal treatments and on-chip detection of biomolecules. The proposed System on-Glass hosts thin metal films acting as heating sources; hydrogenated amorphous silicon diodes acting both as temperature sensors to monitor the temperature distribution and photosensors for the on-chip detection and a ground plane ensuring that the heater operation does not affect the photodiode currents. The sequence of the technological steps, the deposition temperatures of the thin films and the parameters of the photolithographic processes have been optimized in order to overcome all the issues of the technological integration. The device has been designed, fabricated and tested for the implementation of DNA amplification through the Polymerase Chain Reaction (PCR) with thermal cycling among three different temperatures on a single site. The glass has been connected to an electronic system that drives the heaters and controls the temperature and light sensors. It has been optically and thermally coupled with another glass hosting a microfluidic network made in polydimethylsiloxane that includes thermally actuated microvalves and a PCR process chamber. The successful DNA amplification has been verified off-chip by using a standard fluorometer.

This work presents a miniaturized system combining, on the same microfluidic chip, capillarity and electrowetting-on-dielectric (EWOD) techniques for movement and control of fluids. The change in hydrophobicity occurring at the edge between a capillary channel and a hydrophobic layer is successfully exploited as a stop-and-go valve, whose operation is electronically controlled through the EWOD electrodes. Taking into account the variety of microfluidic operation resulting from the combination of the two handling techniques and their characteristic features, this work prompts the development of autonomous, compact and low-power consumption lab-on-chip systems.

In this paper, we present a device that minimizes the effects of the temperature on light detection in lab-on-chip systems. The device is based on hydrogenated amorphous silicon p-type/intrinsic/n-type junction, fabricated on a glass substrate using thin-film technologies. The device structure is constituted by two series-connected amorphous silicon diodes: a blind one acting as dark reference and a photosensitive one. The signal measured at the output node of each element is equal to the difference of the current of the two diodes. This allows to minimize the temperature-dependent dark current contribution. The design of the photolithographic masks has been carefully carried out to pursue a perfect technological symmetry between the two diodes of the differential structure. Experimental data obtained by current-voltage characteristics show the correct operation of the individual diodes as well as the effectiveness of the differential structure to reject the common-mode signal induced by temperature variations. This feature makes the device a suitable candidate for analytical systems based on optical detection that involve thermal treatments.

This paper presents the design, fabrication and characterization of a thin film heater functional for thermal treatments in lab-on-chip system. The spatial temperature distribution determined by different heater geometries has been studied through electro-thermal simulations by using COMSOL Multiphysics. The heater showing the more uniform temperature distribution has been subsequently fabricated and characterized. A very good agreement between modeled and measured data has been attained. Results show a spatial temperature distribution of about ±1°C over an area comparable to the heater area and a directly USB powered heater, demonstrating the suitability of the proposed device for lab-on-chip thermal applications.

In this paper, we present the design and fabrication of Polydimethylsiloxane based Lab-on-Chip system useful for polymerase chain reaction (PCR) application. The proposed system is fabricated on glass substrate, taking advantage of thermally conductive and electrically insulating substrate. On one side of glass microfluidic system having reaction chamber for PCR, microchannel for fluid handling and two thermally actuated valves for fluid control has been made. On the other side of glass three thin film heaters are integrated, two heaters located under valves actuate the valves membrane and allow the chamber isolation and the middle heater is dedicated to PCR thermal cycle. The design of the system, carried out by using COMSOL Multiphysics, involved the optimization of the system dimensions and the shape of microchannel used to completely close the channel. We have also study the thermal interaction between three heaters and optimize the design to minimize the interference. The system was fabricated and an experiment actuating the valves was performed verifying the closing of the microfluidic channel.

In this paper we present a system able to perform thermal treatments on lab-on-chip devices fabricated on glass substrates. The system includes a thin film resistor acting as heater and thin film hydrogenated amorphous silicon diodes acting as temperature sensors. An electronic system controls the lab-on-chip temperature through a Proportional-IntegralDerivative algorithm. In particular, an electronic board infers the system temperature measuring the voltage across the amorphous silicon diodes and drives the heater to achieve the set-point temperature. Taking into account the 16-bit ADC resolution and the sensors sensitivity, which is around 3.6 mV/oC, we estimate that our system is able to detect temperature variation as low as 3.5·10−3 oC. Furthermore, the experimental results show that the system is able to stabilize the system temperature with a precision better than 0.1 oC.