Wireless colorimetric readout to enable resource-limited point-of-care

Patientennahe Diagnostik in Entwicklungsländer birgt spezielle Herausforderungen, die ihren Erfolg bisher begrenzen. Diese Arbeit widmet sich daher der Entwicklung eines in seiner Herstellung skalierbaren und vielseitig einsetzbaren funkbasierten Auslesegerätes für Laborteststreifen. Durch die Kombination einer wachsenden Auswahl an papierbasierten Teststreifendiagnostiken mit gedruckter Elektronik und unter Berücksichtigung des diagnostischen Alltags im südlichen Afrika wurde ein Gerät entwickelt, das Teststreifen zuverlässig ausliest und die Daten per Funk an eine Datenbank übertragen kann. Die Technik basiert auf RFID-Tags (radio frequency identification devices), welche auf verschiedene flexible Substrate gedruckt wurden, um die technische Umsetzbarkeit und Funktionalität zu evaluieren. Um den Preis für die geplante Anwendung niedrig zu halten, wurden unter anderem Papier und Karton als Substrate genutzt. Das Ergebnis dieser Studie sind passive RFID-Tags auf unterschiedlichen, meist günstigen Substraten, die über eine Distanz von über 75 mm betrieben und ausgelesen werden können. Basierend auf der über RFID bereitgestellten Energie und Datenübertragung wurde eine Ausleseeinheit für Standardpapierstreifentests entwickelt und integriert. Durch das Auslesen verschiedener Teststreifen wurde das Gerät evaluiert und in seiner Aussagekraft mit einer scanner-basierten Aufnahme und anschließender Bildanalyse (ImageJ), einem kommerziellen Auslesegerät sowie einer manuellen Auslesung mit Hilfe von Farbtabellen verglichen. Das Gerät kann die Streifen zuverlässig auslesen und die Daten über die RFID-Schnittstelle übertragen. Die funkbasierte Ausleseeinheit ist mit verschiedenen kommerziellen Teststreifen sowohl im biodiagnostischen (lateral flow tests) wie auch im chemischen Bereich (pH-Wert) kompatibel. Die modulare Lösung erlaubt ein breites Einsatzgebiet und führt dadurch zu reduzierten Trainingszeiten der Anwender und einer zuverlässigen Handhabung. Die vorgestellte Lösung ist äußerst kostengünstig und bedarf keiner Wartung, wodurch sie sich sehr gut für den Einsatz in abgelegenen Feldkrankenhäusern eignet. Es wurde ein skalierbarer Prototyp entwickelt, der auf konventionellen Herstellungsverfahren der Verpackungsindustrie aufbaut. Aktuell handelt es sich noch um einen bogenbasierten Prozess, der sich aber prinzipiell auch auf Rolle-zu-Rolle Maschinen übertragen lässt. Bei der Entwicklung des Geräts spielte die Möglichkeit der lokalen Herstellung in den Einsatzländern eine große Rolle. Diese hätte neben der Generierung von Arbeitsplätzen auch den Vorteil einer einfacheren Verteilung der Geräte in ländliche Regionen, in denen sie den größten Nutzen für die Diagnostik erzielen würden

MilkGuard: Low-Cost, Polymer-based Sensor for the Detection of Escherichia coli in Donated Human Breast Milk

Breast milk, the gold standard for infant nutrition, could prevent up to 13% of child deaths worldwide. However, many mothers are unable to breastfeed due to health conditions and other factors. Because of this, a network of more than 500+ human milk banks, which collect and distribute donated breast milk to infants, have emerged worldwide. However, operational costs to ensure the safety of this milk remain time-intensive and costly. There are no existing diagnostics for rapid and on-site detection of bacterial contaminants in donated milk. Currently, many milk banks send samples to outside laboratories for bacterial culturing tests, which take 24-48 hours to receive results. In contrast, MilkGuard is an on-site detection method which ensures results in hours rather than days. To determine whether or not E.coli is present in donated milk, a drop of milk is deposited onto the sensor. If the milk is contaminated, the sensor will turn a blue color due to an enzyme-substrate reaction of the bacteria. The goal of the project is to create a cost and rapid alternative to traditional bacterial culturing testing to screen for E. coli bacteria in donated human breast milk. This will allow users to ensure that milk samples are sterile enough to provide to young infants, while also providing breast milk banks an alternative that will allow them to screen more samples in a shorter amount of time

The impact of printed electronics on product design

Printed electronics (PE) is a disruptive but growing technology that is beginning to integrate its way into viable applications for product design. However, the potential for future impact of the technology on product design and the designer s role and contribution to this has yet to be established. Interest is increasing in the potential for product designers to explore and exploit this technology. Technologies can be seen as being disruptive from both a business, and an adoption point of view. For a business, changing from one technology to another or incorporating a new technology and its production processes can be difficult if they already have their suppliers established and existing relationships in place. Understanding and adopting a new technology can be challenging for a business and individuals working within an established industry as it can cause many questions to be raised around its performance, and direct comparison with the technology they already have in place. However, there have been many technologies that could be seen as disruptive in the past, as they offered an alternative way of working or method of manufacture, such as Bluetooth, 3D printing, and automation (manufacturing/assembly/finishing), etc., and their success has been dictated by individual s perception and adoption of the technology, with their ability to see the worth and potential in the technology. Cost comparison is also an important aspect for a business to consider when choosing whether to change to a new technology or to remain with their existing technology, as changing can disrupt the manufacturing line assembly of a product, and direct cost comparisons of components themselves, such as the cost of buying silicon components in bulk verses printing the components. The new technology needs to offer something different to a product to be worth implementing it in a product, such as its flexible form or lightweight properties of printed electronics being of benefit to the product over what a silicon electronic component/circuit could offer (restricted to rigid circuit boards), the functionality/performance of the components themselves also need to be considered. Performance, availability and maturity of the technology are some of the essential aspects to consider when incorporating a new technology into a product and these can be evaluated using a Technology Readiness Level (TRL) scale. Interest in the stage of development for a technology lies not only with designers; industry and academia also contribute to knowledge by playing a central role in the process of determining a TRL scale that is universally recognised. However, a TRL separation issue occurs between academia (often the technology only reaching an experimental proof of concept stage, a lower number on the TRL scale indicating that the technology is at an early stage of development) and industry (not considering technology for commercialisation until it reaches a stage where there is a demonstration of pre-production capability validated on economic runs, a much higher number on the TRL scale - indicating that the technology is at a much more advanced stage of development). The aim of this doctoral research was to explore the contribution of PE to product design. The researcher experienced the scientific development of the technology first-hand, and undertook a literature review that covered three main topics: 1) printed electronics (the technology itself), 2) impact (approaches to assessing impact and methods of judging new technology) because together they will identify the state of the art of printed electronics technology, and 3) education - educational theories/methods for designers - studying how designers learn, explore different methods in educating them about new technologies, and start to find appropriate methods for educating them about printed electronics technology. A knowledge framework for PE technology was generated and utilised to produce a taxonomy and TRL scale for PE and confirmed by PE expert interview. Existing case studies in which PE technology had been presented to student designers were investigated through interviews with participants from academia and industry to solicit perception and opinions on approaches for the effective communication of PE knowledge to student designers within an educational environment. The findings were interpreted using thematic analysis and, after comparing the data, three main themes identified: technical constraints, designer s perspective, and what a designer is required to do. The findings from the research were combined to create an educational approach for knowledge transfer aimed specifically at meeting the needs of product designers. This resulted in the need for PE technology to be translated into both a visual and written format to create structure and direct links between the technological elements and their form and function in order to facilitate understanding by designers. Conclusions from the research indicate that the translation of this technology into an appropriate design language will equip designers with accessible fundamental knowledge on PE technology (i.e. electrical components: form, function, and area of the technology), which will allow informed decisions to be made about how PE can be used and to utilise its benefits in the design of products. The capabilities and properties of this technology, when paired with product design practice, has the capacity to transform the designs of future products in terms of form/functionality and prevailing/views towards design approaches with electronics. If exposed to a variety of PE elements ranging across different TRLs, designers have the capacity to bridge the TRL separation issue (the gap between academia and industry) through their ability to create design solutions for an end user and provide a commercial application for the technology

New Trends in 3D Printing

A quarter century period of the 3D printing technology development affords ground for speaking about new realities or the formation of a new technological system of digital manufacture and partnership. The up-to-date 3D printing is at the top of its own overrated expectations. So the development of scalable, high-speed methods of the material 3D printing aimed to increase the productivity and operating volume of the 3D printing machines requires new original decisions. It is necessary to study the 3D printing applicability for manufacturing of the materials with multilevel hierarchical functionality on nano-, micro- and meso-scales that can find applications for medical, aerospace and/or automotive industries. Some of the above-mentioned problems and new trends are considered in this book

30 years of microfluidics

Microfluidics provides a great opportunity to create devices capable of outperforming classical techniques in biomedical and chemical research. In this review, the origins of this emerging field in the microelectronics industry are detailed. We also appraise how factors such as government funding influenced the development of new materials and fabrication techniques. Current applications of microfluidics are also examined and we highlight areas where work should be focussed in the future to ensure that the technology realises its full potential

Application of Paper-Based Microfluidic Analytical Devices (µPAD) in Forensic and Clinical Toxicology: A Review

The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, μPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma- hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors

Development of a Dual-Modal Microfluidic Paper-Based Analytical Device for the Quantitative and Qualitative Detection of The Total Hardness of Water.

A dip-and-read microfluidic paper-based analytical device (μPAD) was developed for the qualitative and quantitative detection of the total hardness of water. To create well-defined hydrophobic barriers on filter paper, a regular office printer and a commercially available permanent marker pen were utilized as a quick and simple technique with easily accessible equipment/materials to fabricate μPAD in new or resource-limited laboratories without sophisticated equipment. After a wettability and barrier efficiency analysis on the permanent marker colors, the blue and green ink markers exhibited favorable hydrophobic properties and were utilized in the fabrication of the developed test devices. The device had five reaction and detection zones modeled after the classification given by the World Health Organization (WHO), so qualitatively it determined whether the water was ‘soft’, ‘moderately hard’, ‘hard’, or ‘very hard’ by changing color from blue to pink in about 3 min. The device was also used to introduce an alternative colorimetric reaction for quantitative analysis of the water hardness without the need for ethylenediaminetetraacetic acid (EDTA) and without compromising the simplicity and low cost of the device. The developed μPAD showed a calculated limit of detection (LOD) of 0.02 mM, which is at least 80% less than those of commercially available test strips and other reported μPADs, and the results of the real-world samples were consistent with those of the standard titration (with EDTA). In addition, the device exhibited stability for 2 months at room and frigid condition (4 °C) and at varying harsh temperatures from 25 to 100 °C. The results demonstrate that the developed paper-based device can be used for rapid, on-site analysis of water with no interferences and no need for a pipette for sample introduction during testing. A mathematical estimation of the flow of liquid water and blood serum on the fabricated paper device was computed using a geometrically modified version of the Lucas-Washburn equation to predict the signal time of the paper sensor during each test. The estimation correlated excellently with experimental data and observation, hence making the modification of the Lucas-Washburn equation valid specifically for the fabricated μPAD. Finally, all-inclusive pullulan tablets were fabricated as an alternative analytical platform to detect the total hardness of water. The assay was used to compute a calibration curve which can be used to quantify the total hardness of water in about five minutes by just dropping the required number of tablets in the water sample, and a limit of detection of 0.0140 mM was achieved

Inkjet printing of biological macromolecules for use in biology and medicine

This thesis presents an investigation into the viability of utilising piezoelectric drop on demand printing as a tool for the deposition of proteins for the rapid prototyping of biological sensors. The work has focussed on several main aspects; the effect of printing parameters on drop characteristics, the effect of printing parameters on protein survivability, the influence of surface characteristics on the drop formation at the surface of the sensor, and the electrochemical properties of the sensors after printing. The main objective of this study was to derive a method for the rapid prototyping of sensors using the piezoelectric drop on demand printer. The first section details the influence of waveform amplitude on the characteristics of the printed drop including droplet weight and volume. It was established that proteins were suitable for printing in both a Phosphate buffered saline solution and a sugar based carrier solution as supplied by AET. Protein survivability experiments suggested that there was some loss of activity during the printing process which required further investigation. Research into the effect of printing parameters on the viability of proteins, specifically Glucose Oxidase (GOX) has been categorised according to protein structure and protein conformation. No damage was found to occur to either protein conformation or structure after analysis of the samples using light scattering, analytical centrifugation and circular dichroism after printing at 40, 60 and 80V. Further analysis revealed that there was a loss of mass of protein after the printing process compared to a non printed sample. Surface analysis was employed to quantify the effect of the surface of the electrodes on the drop behaviour after printing through a piezoelectric drop on demand printhead. Proteins were printed onto different carbon surfaces for comparison in different holding solutions and the surfaces analysed for both the drop behaviour when wet and the form and size of the dried enzyme on the carbon surface. Printed samples were observed to spread best with surfactant present in the solution and some evidence of a 'coffee staining effect' was encountered. Further optimisation of the surfactant percentage and the drying conditions ameliorated these effects to produce optimal drying of the solution both on the surface and after drying. An electrochemical technique was also employed to optimise the number of units of enzyme deposited using the printing technique and to ensure that the current response required was achievable and repeatable. After optimisation, it was possible to demonstrate that the 3 unit sample provided a current response with an R2 value greater than 0.99, therefore demonstrating reproducible linearity in the current response. This therefore demonstrated that piezoelectric drop on demand printing techniques could be used for the rapid prototyping of biosensors, especially for use in the glucose sensing market.EThOS - Electronic Theses Online ServiceXaar PlcApplied Enzyme Technologies LtdGBUnited Kingdo

Cellulose-Based Biosensing Platforms

Cellulose empowers measurement science and technology with a simple, low-cost, and highly transformative analytical platform. This book helps the reader to understand and build an overview of the state of the art in cellulose-based (bio)sensing, particularly in terms of the design, fabrication, and advantageous analytical performance. In addition, wearable, clinical, and environmental applications of cellulose-based (bio)sensors are reported, where novel (nano)materials, architectures, signal enhancement strategies, as well as real-time connectivity and portability play a critical role