Clinical Evaluation of Respiratory Rate Measurements on COPD (Male) Patients Using Wearable Inkjet-Printed Sensor.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease that causes long-term breathing problems. The reliable monitoring of respiratory rate (RR) is very important for the treatment and management of COPD. Based on inkjet printing technology, we have developed a stretchable and wearable sensor that can accurately measure RR on normal subjects. Currently, there is a lack of comprehensive evaluation of stretchable sensors in the monitoring of RR on COPD patients. We aimed to investigate the measurement accuracy of our sensor on COPD patients. METHODOLOGY: Thirty-five patients (Mean ± SD of age: 55.25 ± 13.76 years) in different stages of COPD were recruited. The measurement accuracy of our inkjet-printed (IJPT) sensor was evaluated at different body postures (i.e., standing, sitting at 90°, and lying at 45°) on COPD patients. The RR recorded by the IJPT sensor was compared with that recorded by the reference e-Health sensor using paired T-test and Wilcoxon signed-rank test. Analysis of variation (ANOVA) was performed to investigate if there was any significant effect of individual difference or posture on the measurement error. Statistical significance was defined as p-value less than 0.05. RESULTS: There was no significant difference between the RR measurements collected by the IJPT sensor and the e-Health reference sensor overall and in three postures (p > 0.05 in paired T-tests and Wilcoxon signed-rank tests). The sitting posture had the least measurement error of -0.0542 ± 1.451 bpm. There was no significant effect of posture or individual difference on the measurement error or relative measurement error (p > 0.05 in ANOVA). CONCLUSION: The IJPT sensor can accurately measure the RR of COPD patients at different body postures, which provides the possibility for reliable monitoring of RR on COPD patients.

Clinical evaluation of stretchable and wearable inkjet-printed strain gauge sensor for respiratory rate monitoring at different measurements locations.

The respiration rate (RR) is a vital sign in physiological measurement and clinical diagnosis. RR can be measured using stretchable and wearable strain gauge sensors which detect the respiratory movements in the abdomen or thorax areas caused by volumetric changes. In different body locations, the accuracy of RR detection might differ due to different respiratory movement amplitudes. Few studies have quantitatively investigated the effect of the measurement location on the accuracy of new sensors in RR detection. Using a stretchable and wearable inkjet-printed strain gauge (IPSG) sensor, RR was measured from five body locations (umbilicus, upper abdomen, xiphoid process, upper thorax, and diagonal) on 30 healthy test subjects while sitting on an armless chair. At each location, reference RR was simultaneously detected by the e-Health sensor, and the measurement was repeated twice. Subjects were asked about the comfortableness of locations. Based on Levene's test, ANOVA was performed to investigate if there is a significant difference in RR between sensors, measurement locations, and two repeated measurements. Bland-Altman analysis was applied to the RR measurements at different locations. The effects of measurement site and measurement trials on RR difference between sensors were also investigated. There was no significant difference between IPSG and reference sensors, between any locations, and between the two measurements (all p > 0.05). As to the RR deviation between IPSG and reference sensors, there was no significant difference between any locations, or between two measurements (all p > 0.05). All the 30 subjects agreed that diagonal and upper thorax positions were the most uncomfortable and most comfortable locations for measurement, respectively. The IPSG sensor could accurately detect RR at five different locations with good repeatability. Upper thorax was the most comfortable location.

Experimental Characterization of Inkjet-Printed Stretchable Circuits for Wearable Sensor Applications.

This paper introduces a cost-effective method for the fabrication of stretchable circuits on polydimethylsiloxane (PDMS) using inkjet printing of silver nanoparticle ink. The fabrication method, presented here, allows for the development of fully stretchable and wearable sensors. Inkjet-printed sinusoidal and horseshoe patterns are experimentally characterized in terms of the effect of their geometry on stretchability, while maintaining adequate electrical conductivity. The optimal fabricated circuit, with a horseshoe pattern at an angle of 45°, is capable of undergoing an axial stretch up to a strain of 25% with a resistance under 800 Ω. The conductivity of the circuit is fully reversible once it is returned to its pre-stretching state. The circuit could also undergo up to 3000 stretching cycles without exhibiting a significant change in its conductivity. In addition, the successful development of a novel inkjet-printed fully stretchable and wearable version of the conventional pulse oximeter is demonstrated. Finally, the resulting sensor is evaluated in comparison to its commercially available counterpart.

Low Cost Lab on Chip for the Colorimetric Detection of Nitrate in Mineral Water Products.

The diagnostics of health status and the quality of drinking water are among the most important United Nations sustainable development goals. However, in certain areas, wars and instability have left millions of people setting in refugee camps and dangerous regions where infrastructures are lacking and rapid diagnostics of water quality and medical status are critical. In this work, microfluidic testing chips and photometric setups are developed in cheap and portable way to detect nitrate concentrations in water. The performed test is designed to work according to the Griess procedure. Moreover, to make it simple and usable in areas of low resource settings, commercially available Arduino mega and liquid crystal display (LCD) shield are utilized to process and display results, respectively. For evaluation purposes, different local products of tap water, bottled drinking water, and home-filter treated water samples were tested using the developed setup. A calibration curve with coefficient of determination (R²) of 0.98 was obtained when absorbance of the prepared standard solutions was measured as a function of the concentrations. In conclusion, this is the first step towards a compact, portable, and reliable system for nitrate detection in water for point-of-care applications.

Characterization of oxygen transfer in vertical microbubble columns for aerobic biotechnological processes.

This paper presents the applicability of a microtechnologically fabricated microbubble column as a screening tool for submerged aerobic cultivation. Bubbles in the range of a few hundred micrometers in diameter were generated at the bottom of an upright-positioned microdevice. The rising bubbles induced the circulation of the liquid and thus enhanced mixing by reducing the diffusion distances and preventing cells from sedimentation. Two differently sized nozzles (21 × 40 µm(2) and 53 × 40 µm(2) in cross-section) were tested. The gas flow rates were adjustable, and the resulting bubble sizes and gas holdups were investigated by image analysis. The microdevice features sensor elements for the real-time online monitoring of optical density and dissolved oxygen. The active aeration of the microdevice allowed for a flexible oxygen supply with mass transfer rates of up to 0.14 s(-1). Slightly higher oxygen mass transfer rates and a better degassing were found for the microbubble column equipped with the smaller nozzle. To validate the applicability of the microbubble column for aerobic submerged cultivation processes, batch cultivations of the model organism Saccharomyces cerevisiae were performed, and the specific growth rate, oxygen uptake rate, and yield coefficient were investigated.

An in-line photonic biosensor for monitoring of glucose concentrations.

This paper presents two PDMS photonic biosensor designs that can be used for continuous monitoring of glucose concentrations. The first design, the internally immobilized sensor, consists of a reactor chamber, micro-lenses and self-alignment structures for fiber optics positioning. This sensor design allows optical detection of glucose concentrations under continuous glucose flow conditions of 33 µL/h based on internal co-immobilization of glucose oxidase (GOX) and horseradish peroxidase (HRP) on the internal PDMS surface of the reactor chamber. For this design, two co-immobilization methods, the simple adsorption and the covalent binding (PEG) methods were tested. Experiments showed successful results when using the covalent binding (PEG) method, where glucose concentrations up to 5 mM with a coefficient of determination (R2) of 0.99 and a limit of detection of 0.26 mM are detectable. The second design is a modified version of the internally immobilized sensor, where a microbead chamber and a beads filling channel are integrated into the sensor. This modification enabled external co-immobilization of enzymes covalently onto functionalized silica microbeads and allows binding a huge amount of HRP and GOX enzymes on the microbeads surfaces which increases the interaction area between immobilized enzymes and the analyte. This has a positive effect on the amount and rate of chemical reactions taking place inside the chamber. The sensor was tested under continuous glucose flow conditions and was found to be able to detect glucose concentrations up to 10 mM with R2 of 0.98 and a limit of detection of 0.7 mM. Such results are very promising for the application in photonic LOC systems used for online analysis.

Monitoring Symptoms of Infectious Diseases: Perspectives for Printed Wearable Sensors.

Infectious diseases possess a serious threat to the world's population, economies, and healthcare systems. In this review, we cover the infectious diseases that are most likely to cause a pandemic according to the WHO (World Health Organization). The list includes COVID-19, Crimean-Congo Hemorrhagic Fever (CCHF), Ebola Virus Disease (EBOV), Marburg Virus Disease (MARV), Lassa Hemorrhagic Fever (LHF), Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), Nipah Virus diseases (NiV), and Rift Valley fever (RVF). This review also investigates research trends in infectious diseases by analyzing published research history on each disease from 2000-2020 in PubMed. A comprehensive review of sensor printing methods including flexographic printing, gravure printing, inkjet printing, and screen printing is conducted to provide guidelines for the best method depending on the printing scale, resolution, design modification ability, and other requirements. Printed sensors for respiratory rate, heart rate, oxygen saturation, body temperature, and blood pressure are reviewed for the possibility of being used for disease symptom monitoring. Printed wearable sensors are of great potential for continuous monitoring of vital signs in patients and the quarantined as tools for epidemiological screening.

High-Efficiency Small Sample Microparticle Fractionation on a Femtosecond Laser-Machined Microfluidic Disc.

The fabrication and testing of microfluidic spinning compact discs with embedded trapezoidal microchambers for the purpose of inertial microparticle focusing is reported in this article. Microparticle focusing channels require small features that cannot be easily fabricated in acrylic sheets and are complicated to realize in glass by traditional lithography techniques; therefore, the fabrication of microfluidic discs with femtosecond laser ablation is reported for the first time in this paper. It could be demonstrated that high-efficiency inertial focusing of 5 and 10 µm particles is achieved in a channel with trapezoidal microchambers regardless of the direction of disc rotation, which correlates to the dominance of inertial forces over Coriolis forces. To achieve the highest throughput possible, the suspension concentration was increased from 0.001% (w/v) to 0.005% (w/v). The focusing efficiency was 98.7% for the 10 µm particles and 93.75% for the 5 µm particles.

Development of Active Centrifugal Pump for Microfluidic CD Platforms.

The continuous emerging of microfluidic compact disc (CD) platforms for various real-life applications motivates researchers to explore new innovative ideas towards more integrated active functions. However, microfluidic CDs have some drawbacks, including the unidirectional flow that limits the usable space for multi-stepped biological and chemical assays. In this work, a novel active and bidirectional centrifugal pump is developed and integrated on microfluidic CDs. The design of the developed pump partially replicates the designs of the conventional centrifugal pumps with a modification in the connecting channels' positions that allow the developed pump to be reversible. The main advantage of the proposed centrifugal pump is that the pumping speed can be accurately controlled during spinning or while the microfluidic CD is stationary. Performance tests show that the pumping speed can reach up to 164.93 mm3/s at a pump rotational speed (impellers speed) of 4288 rpm. At that speed, 1 mL of water could be pumped in 6.06 s. To present a few of the potential applications of the centrifugal pump, flow reciprocation, bidirectional pumping, and flow switching were performed and evaluated. Results show that the developed centrifugal pump can pump 1096 µL of liquid towards the CD center at 87% pumping efficiency while spinning the microfluidic CD at 250 rpm. This novel centrifugal pump can significantly widen the range of the applicability of microfluidic CDs in advanced chemical processes and biological assays.

Sheath-less high throughput inertial separation of small microparticles in spiral microchannels with trapezoidal cross-section.

Various mechanisms of different designs have emerged for the purpose of microparticle separation and cell sorting. The main goals behind such designs are to create high throughput and high purity sample isolation. In this study, high efficiency, high throughput and precise separation of microparticles under inertial lift and drag forces induced by trapezoidal curvilinear channels are reported. This work is the first to focus and recover 2 from 5 µm and 2 from 10 µm particles in spiral channels in a sheath-less flow device, which reduces the overall complexity of the system and allows for higher throughput. The new microfluidic chip design is fabricated in glass using femtosecond laser ablation. In addition, mathematical force calculations were conducted during the design phase of the microfluidic channels and compared with experiments. The results show a close prediction of the equilibrium position of the tested microparticles.

Fabrication and Evaluation of a Novel Non-Invasive Stretchable and Wearable Respiratory Rate Sensor Based on Silver Nanoparticles Using Inkjet Printing Technology.

The respiration rate (RR) is a key vital sign that links to adverse clinical outcomes and has various important uses. However, RR signals have been neglected in many clinical practices for several reasons and it is still difficult to develop low-cost RR sensors for accurate, automated, and continuous measurement. This study aims to fabricate, develop and evaluate a novel stretchable and wearable RR sensor that is low-cost and easy to use. The sensor is fabricated using the soft lithography technique of polydimethylsiloxane substrates (PDMS) for the stretchable sensor body and inkjet printing technology for creating the conductive circuit by depositing the silver nanoparticles on top of the PDMS substrates. The inkjet-printed (IJP) PDMS-based sensor was developed to detect the inductance fluctuations caused by respiratory volumetric changes. The output signal was processed in a Wheatstone bridge circuit to derive the RR. Six different patterns for a IJP PDMS-based sensor were carefully designed and tested. Their sustainability (maximum strain during measurement) and durability (the ability to go bear axial cyclic strains) were investigated and compared on an automated mechanical stretcher. Their repeatability (output of the sensor in repeated tests under identical condition) and reproducibility (output of different sensors with the same design under identical condition) were investigated using a respiratory simulator. The selected optimal design pattern from the simulator evaluation was used in the fabrication of the IJP PDMS-based sensor where the accuracy was inspected by attaching it to 37 healthy human subjects (aged between 19 and 34 years, seven females) and compared with the reference values from e-Health nasal sensor. Only one design survived the inspection procedures where design #6 (array consists of two horseshoe lines) indicated the best sustainability and durability, and went through the repeatability and reproducibility tests. Based on the best pattern, the developed sensor accurately measured the simulated RR with an error rate of 0.46 ± 0.66 beats per minute (BPM, mean ± SD). On human subjects, the IJP PDMS-based sensor and the reference e-Health sensor showed the same RR value, without any observable differences. The performance of the sensor was accurate with no apparent error compared with the reference sensor. Considering its low cost, good mechanical property, simplicity, and accuracy, the IJP PDMS-based sensor is a promising technique for continuous and wearable RR monitoring, especially under low-resource conditions.

Enhanced inertial focusing of microparticles and cells by integrating trapezoidal microchambers in spiral microfluidic channels.

In this work, manipulating width and equilibrium position of fluorescent microparticles in spiral microchannel fractionation devices by embedding microchambers along the last turn of a spiral is reported. Microchambers with different shapes and sizes were tested at Reynolds numbers between 15.7 and 156.6 (100-1000 µL min-1) to observe focusing of 2, 5 and 10 µm fluorescent microparticles. This paper also discusses the fabrication process of the microfluidic chips with femtosecond laser ablation on glass wafers, as well as a particle imaging velocimetry (µPIV) study of microparticle trajectories inside a microchamber. It could be demonstrated with an improved final design with inclined microchamber side walls, that the 2 µm particle equilibrium position is shifted towards the inner wall by ∼27 µm and the focusing line's width is reduced by ∼18 µm. Finally, Saccharomyces cerevisiae yeast cells were tested in the final chip and a cell focusing efficiency of 99.1% is achieved.

Optimization of Geometry Parameters of Inkjet-Printed Silver Nanoparticle Traces on PDMS Substrates Using Response Surface Methodology.

Inkjet printing is an emerging technology with key advantages that make it suitable for the fabrication of stretchable circuits. Specifically, this process is cost-effective and less complex compared to conventional fabrication technologies. Inkjet printing has several process and geometry parameters that significantly affect the electromechanical properties of the printed circuits. This study aims to optimize the geometry parameters of inkjet-printed silver nanoparticle traces on plasma-treated polydimethylsiloxane (PDMS) substrates. The optimization process was conducted for two printed shapes, namely straight line and horseshoe patterns. The examined input factors for the straight line traces were: the number of inkjet-printed layers and line width. On the other hand, the number of cycles and amplitude were the examined input parameters for the horseshoe shape. First, the optimal number of layers and line width were found from the straight line analysis and subsequently were used in the optimization of the horseshoe pattern parameters. The optimization of the input parameters was carried out using the response surface methodology (RSM), where the objective of the optimization was to maximize the breakdown strain of the traces while maximizing the gauge factor and minimizing the ink cost. The results indicate that a 1.78 mm line width and one layer are the optimal geometry parameters for the straight line traces, while for the horseshoe pattern, the optimal parameters are one layer, a line width of 1.78 mm, amplitude of 4 mm and one cycle. The optimal straight line was designed to sustain up to 10% strain while the horseshoe pattern was designed to sustain up to 15% strain.

Lab on a Chip for the Colorimetric Determination of Nitrite in Processed Meat Products in the Jordanian Market.

Nitrite and Nitrate have been used extensively as additives in various meat products to enhance flavor, color, and to preserve the meat from the bacterial growth. High concentrations of nitrite can threat human health since several studies in the literature claim that nitrite is associated with cancer incidences, leukemia, and brain tumors. Therefore, it is vital to measure the nitrite concentrations in processed meat products. In this study, an in-lab miniaturized photometric detection system is fabricated to inspect the nitrite concentration in processed meat products in Jordan. The analytical performance of nitrite detection is evaluated based on three key statistical parameters; linearity, limit of detection, and limit of quantitation. Respectively, for the fabricated system, the three values are found to be equal to 0.995, 1.24 × 10-2 ppm, and 4.12 × 10-2 ppm. Adherence to Beer's law is found over the investigated range from 2.63 ppm to 96.0 ppm. The developed system is utilized for photometric detection of nitrite in processed meat products available in the Jordanian market like pastrami, salami, and corned beef. In all of the analyzed samples, the nitrite content is found to be lower than 150 ppm, which represents the maximum allowable nitrite limit.

Fabrication of Stretchable Circuits on Polydimethylsiloxane (PDMS) Pre-Stretched Substrates by Inkjet Printing Silver Nanoparticles.

Several research methodologies have recently been developed to allow for the patterning of conductive lines on elastomeric rubber substrates. Specifically, various conductive materials, substrates, and fabrication techniques were investigated to develop stretchable circuits. One promising technique recommends the application of axial strain on an elastomer substrate prior to patterning conductive lines on it. When the substrate is released, conductive lines buckle to form waves, making the circuit stretchable. However, the majority of applications of stretchable circuits require fitting them to two-dimensional surfaces, such as the human body. Hence, in this paper we propose the concept of radial pre-stretching of the substrates to enhance the stretchability of the fabricated circuits. In particular, straight silver conductive lines were deposited on a polydimethylsiloxane (PDMS) surface using inkjet printing technology, and subsequently tested under both axial and radial loads. Radial pre-stretching was compared to axial pre-stretching, resulting in an improved performance under radial loads. The optimal performance was achieved by pre-stretching the PDMS substrate with a radial strain of 27%. This resulted in stretchable circuits which could sustain radial loads with an average breakdown strain of approximately 19%. Additionally, horseshoe patterns were printed on radially pre-stretched PDMS substrates and their performance was compared to that of their straight line counterparts. Though these patterns are generally favorable for the fabrication of stretchable circuits, the optimal horseshoe pattern examined in this study could only sustain up to 16% radial strain on average when radially pre-stretched by 27%.

Spiral Microchannels with Trapezoidal Cross Section Fabricated by Femtosecond Laser Ablation in Glass for the Inertial Separation of Microparticles.

The fabrication and testing of spiral microchannels with a trapezoidal cross section for the passive separation of microparticles is reported in this article. In contrast to previously reported fabrication methods, the fabrication of trapezoidal spiral channels in glass substrates using a femtosecond laser is reported for the first time in this paper. Femtosecond laser ablation has been proposed as an accurate and fast prototyping method with the ability to create 3D features such as slanted-base channels. Moreover, the fabrication in borosilicate glass substrates can provide high optical transparency, thermal resistance, dimensional stability, and chemical inertness. Post-processing steps of the laser engraved glass substrate are also detailed in this paper including hydrogen fluoride (HF) dipping, chemical cleaning, surface activation, and thermal bonding. Optical 3D images of the fabricated chips confirmed a good fabrication accuracy and acceptable surface roughness. To evaluate the particle separation function of the microfluidic chip, 5 µm, 10 µm, and 15 µm particles were focused and recovered from the two outlets of the spiral channel. In conclusion, the new chemically inert separation chip can be utilized in biological or chemical processes where different sizes of cells or particles must be separated, i.e., red blood cells, circulating tumor cells, and technical particle suspensions.

New generation of spinning systems for robust active mixing on microfluidic CDs: oil/water emulsion as an evaluation test.

Microfluidic CDs (or Lab-on-Disc) continue to emerge in various applications of real life sciences, including biomedical and pharmaceutical fields. However, microfluidic CDs with advanced and efficient unit operation tools, such as pumping, valving, and mixing, need to be implemented to achieve the required applications in these fields. In this work, a novel generation of a spinning system to perform robust active mixing is developed for microfluidic CDs. The developed system is equipped with a dual-motor and dual-CD configuration to perform magnetically driven active mixing. The results show that the developed spinning system can provide a wide range of mixing frequencies independent of the spinning speed of the microfluidic CD. To evaluate the performance of this system under extreme conditions, an emulsion process of oil and water was conducted. Although the oil produced high drag force on the mixing magnet, the emulsion process successfully reached a steady state of mixing within a few seconds (approximately 3.5 s), and the mixture became homogeneous at 75 seconds. To demonstrate one of the potential applications of the proposed developed spinning setup, microparticles were successfully extracted from water to oil using water/oil emulsion on the microfluidic CD. In conclusion, mixing can be performed without influencing the integrated microfluidic components such as valves or pumps. This improvement can widen the range of applicability of microfluidic CDs in multi-step and complex processes where mixing is essential.

LEGO Mindstorms NXT for elderly and visually impaired people in need: A platform.

This paper presents the employment of LEGO Mindstorms NXT robotics as core component of low cost multidisciplinary platform for assisting elderly and visually impaired people. LEGO Mindstorms system offers a plug-and-play programmable robotics toolkit, incorporating construction guides, microcontrollers and sensors, all connected via a comprehensive programming language. It facilitates, without special training and at low cost, the use of such device for interpersonal communication and for handling multiple tasks required for elderly and visually impaired people in-need. The research project provides a model for larger-scale implementation, tackling the issues of creating additional functions in order to assist people in-need. The new functions were built and programmed using MATLAB through a user friendly Graphical User Interface (GUI). Power consumption problem, besides the integration of WiFi connection has been resolved, incorporating GPS application on smart phones enhanced the guiding and tracking functions. We believe that developing and expanding the system to encompass a range of applications beyond the initial design schematics to ease conducting a limited number of pre-described protocols. However, the beneficiaries for the proposed research would be limited to elderly people who require assistance within their household as assistive-robot to facilitate a low-cost solution for a highly demanding health circumstance.

Vertical microbubble column-A photonic lab-on-chip for cultivation and online analysis of yeast cell cultures.

This paper presents a vertically positioned microfluidic system made of poly(dimethylsiloxane) (PDMS) and glass, which can be applied as a microbubble column (µBC) for biotechnological screening in suspension. In this µBC, microbubbles are produced in a cultivation chamber through an integrated nozzle structure. Thus, homogeneous suspension of biomass is achieved in the cultivation chamber without requiring additional mixing elements. Moreover, blockage due to produced carbon dioxide by the microorganisms-a problem predominant in common, horizontally positioned microbioreactors (MBRs)-is avoided, as the gas bubbles are released by buoyancy at the upper part of the microsystem. The patterned PDMS layer is based on an optimized two-lithographic process. Since the naturally hydrophobic PDMS causes problems for the sufficient production of microbubbles, a method based on polyelectrolyte multilayers is applied in order to allow continuous hydrophilization of the already bonded PDMS-glass-system. The µBC comprises various microelements, including stabilization of temperature, control of continuous bubble formation, and two optical configurations for measurement of optical density with two different sensitivities. In addition, the simple and robust application and handling of the µBC is achieved via a custom-made modular plug-in adapter. To validate the scalability from laboratory scale to microscale, and thus to demonstrate the successful application of the µBC as a screening instrument, a batch cultivation of Saccharomyces cerevisiae is performed in the µBC and compared to shake flask cultivation. Monitoring of the biomass growth in the µBC with the integrated online analytics resulted in a specific growth rate of 0.32 h(-1), which is almost identical to the one achieved in the shake flask cultivation (0.31 h(-1)). Therefore, the validity of the µBC as an alternative screening tool compared to other conventional laboratory scale systems in bioprocess development is proven. In addition, vertically positioned microbioreactors show high potential in comparison to conventional screening tools, since they allow for high density of integrated online analytics and therefore minimize time and cost for screening and guarantee improved control and analysis of cultivation parameters.