Deep Vein Thrombosis and pulmonary embolism (DVT/PE) is one of the most common causes of unexpected death for hospital in-patients. D-dimer is used as a biomarker within blood for the diagnosis of DVT/PE. We report a low-cost microfluidic device with a conveniently biofunctionalised interdigitated electrode (IDE) array and a portable impedimetric reader as a point-of-care (POC) device for the detection of D-dimer to aid diagnosis of DVT/PE. The IDE array elements, fabricated on a polyethylenenaphtalate (PEN) substrate, are biofunctionalised in situ after assembly of the microfluidic device by electropolymerisation of a copolymer of polypyrrole to which is immobilised a histidine tag anti-D-Dimer antibody. The most consistent copolymer films were produced using chronopotentiometry with an applied current of 5μA for a period of 50 s using a two-electrode system. The quality of the biofunctionalisation was monitored using optical microscopy, chronopotentiometry curves and impedimetric analysis. Measurement of clinical plasma sample with a D-dimer at concentration of 437 ng/mL with 15 biofunctionalised IDE array electrodes gave a ratiometric percentage of sample reading against the blank with an average value of 124 ± 15 at 95% confidence. We have demonstrated the concept of a low cost disposable microfluidic device with a receptor functionalised on the IDE array for impedimetric detection towards POC diagnostics. Changing the receptor on the IDE array would allow this approach to be used for the direct detection of a wide range of analytes in a low cost manner.

Deep Vein Thrombosis and pulmonary embolism (DVT/PE) is one of the most common causes of unexpected death for hospital in-patients.D-dimer is used as a biomarker within blood for the diagnosis of DVT/PE.We report a low-cost microfluidic device with a conveniently biofunctionalised interdigitated electrode (IDE) array and a portable impedimetric reader as a point-of-care (POC) device for the detection of Ddimer to aid diagnosis of DVT/PE.The IDE array elements, fabricated on a polyethylenenaphtalate (PEN) substrate, are biofunctionalised in situ after assembly of the microfluidic device by electropolymerisation of a copolymer of polypyrrole to which is immobilised a histidine tag anti-D-Dimer antibody.The most consistent copolymer films were produced using chronopotentiometry with an applied current of 5A for a period of 50 seconds using a two-electrode system.The quality of the biofunctionalisation was monitored using optical microscopy, chronopotentiometry curves and impedimetric analysis.Measurement of clinical plasma sample with a Ddimer at concentration of 437 ng/mL with 15 biofunctionalised IDE array electrodes gave a ratiometric percentage of sample reading against the blank with an average value of 124±15 at 95% confidence.We have demonstrated the concept of a low cost disposable microfluidic device with a receptor functionalised on the IDE array for impedimetric detection towards POC diagnostics.Changing the receptor on the IDE array would allow this approach to be used for the direct detection of a wide range of analytes in a low cost manner.

In this study, we introduce a three dimensional Slipdisc1 based on slipchip technology, aimed to be used at detection of HIV-1 viral load in resource limited settings. This method is based on magne ...

We report on multiplexed detection of SNPs (Single Nucleotide Polymorphisms) in a low-cost foil-based microfluidic detection module using small multichannel Silicon Photomultiplier detectors (SiPM). The microfluidic module uses integrated DNA microarrays and thin-film microheaters to enable surface-bound melting curve analysis (MCA) for SNP scoring.

Point-of-Care (POC) diagnostics often fail to meet the market requirements of low cost and advanced functionality, and are often limited to lateral flow based serological diagnostics with reduced sensitivity and specificity. We report here on an integrated microfluidic absorbance measurement device fabricated by roll-to-roll (R2R) compatible manufacturing processes, suitable for low cost POC systems. It is a device exclusively made of foils and takes external light from a low cost LED and converts the point light source to a homogeneous light via a foil based optical filter at the bottom of the device. The light is converted to an electrical signal by an amorphous organic semiconductor (OSC) material, integrated with screen-printed carbon finger on top of the device for electrical measurement. As a proof of principle, we demonstrate DNA hybridization assay, where the target DNA is coupled to magnetic beads for absorbance measurement. The device successfully distinguishes between matched and mismatched DNA hybridization and can differentiate between 1 mu M, 50 nM and 2.5 nM DNA target concentrations. The inherent characteristics of the substrates and R2R fabrication concept significantly reduce the cost, making it suitable for POC applications at resource-limited settings. (c) 2017 Elsevier B.V. All rights reserved.

We report detection of single nucleotide polymorphisms (SNP) by melting curve analysis (MCA) on DNA microarrays in a plastic microfluidic system with integrated heaters using lamination foils. Thin-film copper microheaters were structured on polyethylene napthalate (PEN) foil and DNA microarrays were printed on the heater foil. The system was integrated in a microfluidic channel and successful detection of SNPs was demonstrated. Thermal and electrical characterization of the system was performed proving that the recently implemented low-cost heater encapsulation method using a simple single-sided adhesive foil has not affected the systems performance relative the previous Parylene C encapsulation.

We report on DNA genotyping by melting curve analysis (MCA) in a plastic foil-microfluidic system using silicon photomultiplier (SiPM) detectors. Matching and single base mismatching DNA oligonucleotides were immobilized on thin-film foil microheaters and integrated in microfluidic channels using lamination foils. Two SiPMs, each with a sensitive area of 1.2×1.2 mm were assembled in an optical measurement setup to monitor the decaying Cy3 fluorescence intensity of the hybridized DNA spots upon melting. Successful detection of single nucleotide polymorphisms (SNP) is demonstrated.

We report on genotyping of single nucleotide polymorphisms (SNP) by melting curve analysis (MCA) on DNA microarrays in a plastic microfluidic system with integrated heaters using lamination foils. ...

The recent technological advances in micro/nanotechnology present new opportunities to combine microfluidics with microarray technology for the development of small, sensitive, single-use, point-of-care molecular diagnostic devices. As such, the integration of microarray and plastic microfluidic systems is an attractive low-cost alternative to glass based microarray systems. This paper presents the integration of a DNA microarray and an all-polymer microfluidic foil system with integrated thin film heaters, which demonstrate DNA analysis based on melting curve analysis (MCA). A novel micro-heater concept using semi-transparent copper heaters manufactured by roll-to-roll and lift-off on polyethylene naphthalate (PEN) foil has been developed. Using a mesh structure, heater surfaces have been realized in only one single metallization step, providing more efficient and homogenous heating characteristics than conventional meander heaters. A robust DNA microarray spotting protocol was adapted on Parylene C coated heater-foils, using co-polymer poly(DMA-NAS-MAPS) to enable covalent immobilization of DNA. The heaters were integrated in a microfluidic channel using lamination foils and MCA of the spotted DNA duplexes showed single based discrimination of mismatched over matched target DNA-probes. Finally, as a proof of principle, we perform MCA on PCR products to detect the Leu7Pro polymorphism of the neutropeptide Y related to increased risk of Type II diabetes, BMI and depression.

In this paper, we report on a novel device that addresses the needs for an efficient, field deployable and disposable system in the field of bio-chemical sensors using organic semiconductors. The Fraunhofer Institute has enabled a complete roll-to-roll manufactured polymer-opto-chemical-electronic module on a foil substrate, wherein an electroluminescent light source has been hetero-integrated together with an organic TFT, working as a photo detector. A chemically sensitive, colour changing film is sandwiched in between the two elements to form an optical detection system for volatile analytes such as amines. The setup, henceforth referred to as the “PolyOpto” module, comprises of a dye coated layer that can detect specific chemical reactions by colour change inserted in between the EL light source and the OTFT photo-detector. A hole is laser cut through the system to allow the sensor layer to come in contact with the gases, which then through a chemical reaction, changes colour and initiates a different response in the output of the organic transistor. Hence, this allows for a disposable chemo-analytical system that can be used in various application fields. As compared to conventional systems, the advantage here lies in the direct integration of the different functionalities without any advanced assembly steps, simultaneous use of coatings for both components (transparent electrode and wiring layer) and roll-to-roll compatibility, thus rendering a disposable system. We believe that it aptly demonstrates the capabilities of polytronics in functional integration for low-cost bio-sensor manufacturing.

This paper presents a multi-functional operational diagnostic lab-on-foil analysis system integrating electrical and optical devices by polytronic means. This functional polymer-opto-electronic module is completely integrated on a foil substrate, where an electroluminescent light source has been hetero-integrated together with an organic thin-film field-effect transistor (OTFT), working as a photodetector. This module is combined with a microfluidic channel also machined in plastics to form an optical detection system for analysis of fluids. The different components are fabricated on a PEN film substrate with coating and patterning steps, resulting in direct integration of the different functionalities without any assembly steps. Therefore a very cost-efficient way of fabricating such a module is achieved. Furthermore the use of plastic films as substrate opens the way to low-cost manufacturing with roll-to-roll processing. The module demonstrates in this way the capabilities of polytronics in functional integration for low-cost manufacturing.

This paper reports the development and characterisation of an assembly technology for a polymer lab-on-chip. The system consists of a 150 μm deep hot embossed microfluidic channel in polycarbonate and Au electrodes fabricated separately by photolithography on polyethylenenaphthalate. The system is designed for impedimetric immunoassay detection in whole blood. Electrode layer and microfluidic substrate are joined by means of a 50 μm thick double-sided medical grade adhesive tape, adjusted with an optical alignment system. The bond proved to be liquid tight at room temperature. An alignment accuracy of 34 μm (+/- 19 μm) evaluated over a set of 23 samples, was achieved. The effect of alignment accuracy of the intermediate adhesive film on whole blood flow properties in the device is studied. Already an alignment error of 70 μm increases the flushing out time of whole blood by approximately 20%.

Ein Mikrofluidikmodul zur Analyse von Fluiden weist ein einstuckiges Tragersubstrat mit einer ersten Hauptoberflache und einer gegenuberliegenden zweiten Hauptoberflache auf. Weiterhin weist das Mikrofluidikmodul eine Sensoranordnung auf, wobei ein erstes Funktionselement der Sensoranordnung an einem ersten Oberflachenbereich des Tragersubstrats angeordnet ist. Das Mikrofluidikmodul weist ferner eine Kanalstruktur auf, die mit der ersten Hauptoberflache des Tragersubstrats verbunden ist, so dass sich ein Kanalbereich zwischen dem ersten Oberflachenbereich des Tragersubstrats und einem, dem ersten Oberflachenbereich gegenuberliegenden zweiten Oberflachenbereich des Tragersubstrats ausbildet, der von der Kanalstruktur und dem Tragersubstrat umgeben ist.

This paper presents SNP scoring by DASH technology by employing dynamic heating of beads immobilized on a chip with integrated heater and sensor. The microfabricated chip designed for open-surface DNA analysis allows fast, well controllable temperature ramping and homogeneous temperature distribution over the entire heater area. Beads containing DNA duplexes are immobilized on the surface of the chip by microcontact printing using a PDMS stamp. All three possible variants of a SNP site of an oligonucleotide were accurately scored using the bead-based DASH approach. Using the chip, the total analysis time could easily be reduced by a factor 2 compared with the current DASH assay.

This paper presents genotyping on a novel microheater concept using semi-transparent copper microheaters manufactured by roll-to-roll and lift-off on polyethylene napthalate (PEN) foil. Using a mesh structure, heater surfaces have been realized in one single metallization step with a manufacturing robustness higher than conventional meander structures. The thermal distribution of the meshes, evaluated using thermochromic-liquid-crystals (TLC), produced more homogenous heating characteristics compared to meanders. Parylene coated heaters were functionalized using copolymer poly(DMA-NAS-MAPS) to enable covalent DNA immobilization and successful melting curve analysis was performed differentiating between match and mismatch oligonucleotides.