Impedimetric array in polymer microfluidic cartridge for low cost point-of-care diagnostics

International audienc

Foil-based Lab-on-Chip technologies for advanced Point-of-Care molecular diagnostics

Infectious diseases pose a serious threat to global health. Molecular diagnostics provide solutions for effective control and prevention of infections, however suffers from expensive laboratory equipment, and infrastructure to be fully implemented at point of care (POC), especially at low-resource settings. Lab-on-a-chip that aims to integrate complex biochemical analyses into automated systems is promising for POC analysis. A major challenge is the integration of a complete molecular diagnostic assay, generally translating into complex microfluidics, with the requirement of low fabrication cost. This thesis explores the use of flexible electronics, plastic foils and roll-to-roll manufacturing to enable low-cost microfluidic systems, for molecular diagnostic assays especially targeted towards infectious diseases. Many biochemical assays rely on heat; hence a first aspect in this thesis is the integration of a microheater into microfluidics. In a first project a system for SNP-genotyping is presented using solid phase melting curve analysis to discriminate mutations at a single base resolution. Starting with a glass based concept (paper I) which is further developed to a foil based system (paper II), detection of the polymorphism in the neuropeptide Y associated with increased risk of type II diabetes is demonstrated as a proof of principle. Further development and optimization of the microheater concept has enabled roll-to-roll manufacturing compatibility and multiplexing of targets (paper III). A bacterial sub-typing and multiresistance detection in clinical Staphylococcus Aureus samples is demonstrated for applications in infectious diseases diagnostics. Finally, the microheater concept is further developed to enable μPCR (paper IV). Detection of genomic HIV-1 is demonstrated and a portable detection setup based on an LED light source and low cost CMOS camera for detection was developed. A second aspect of this thesis is integration of light sources and optical detection (paper V-VI). A multilayer system integrating an electroluminescent light source, reactive sensor dyes and organic semiconductor transistor for detection is demonstrated. The system could be used for amine detection in gases (paper V). System was made further roll-to-roll compatible. The system uses an external LED light source and a photodetector processed in only one screen printing- and one dispensing step (paper VI). As a proof of principle, absorbance based DNA hybridization was detected. Collectively, roll-to-roll manufacturing compatible “lab on foil” systems have the potential to improve our ability to diagnose at POC especially at resource-limited settings.QC 20170426</p

Three dimensional Slipdisc aimed at HIV viral load detection

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 magnetic bead based isolation of RNA from sample, followed by release of RNA in an elution buffer, followed by amplification of the initial concentration of RNA in an elution buffer. The novelty is the extraction method which is a one step method and involves using magnetic beads attached to sample DNA to pass through an immiscible oil phase2 for one step washing.QC 20190819</p

Three dimensional Slipdisc aimed at HIV viral load detection

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 magnetic bead based isolation of RNA from sample, followed by release of RNA in an elution buffer, followed by amplification of the initial concentration of RNA in an elution buffer. The novelty is the extraction method which is a one step method and involves using magnetic beads attached to sample DNA to pass through an immiscible oil phase2 for one step washing.QC 20190819</p

Three dimensional Slipdisc aimed at HIV viral load detection

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 magnetic bead based isolation of RNA from sample, followed by release of RNA in an elution buffer, followed by amplification of the initial concentration of RNA in an elution buffer. The novelty is the extraction method which is a one step method and involves using magnetic beads attached to sample DNA to pass through an immiscible oil phase2 for one step washing.QC 20190819</p

Staphylococcus aureus sub-typing and detection of MRSA on a microfluidic lab-on-foil device

Emerging antibiotic multi-resistance, increased travel and trade, and environmental changes have contributed to the prevalence of infectious diseases and rapid changes in the efficiency of therapeutics. We report detection of multi-resistant Staphylococus aureus and S. aureus strain sub-types using a microfluidic detection module with integrated thin film heater and DNA microarray, which enables surface-bound melting curve analysis. Successful discrimination between clinical S. aureus strain sub-types and between methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) was demonstrated. The microfluidic detection module is constructed completely on a plastic foil using roll-to-roll compatible fabrication methods that yield a very low-cost system.</p