Microfluidic Sensing Platforms for Medicine and Diagnostics

In: Kiilerich-Pedersen , K 2013 , Microfluidic Sensing Platforms for Medicine and Diagnostics . Technical University of Denmark , Kgs. Lyngby .

Open Access

Abstract

Infektiøse sygdomme udgør en stadig større global udfordring når det kommer til diagnostik, behandling og offentlig sundhedspolitik. Biosensorer er en af de hurtigst voksende teknologier indenfor in vitro diagnostik. De sofistikerede mikrosystemer åbner op for spændende decentraliserede kliniske anvendelsesmuligheder i medicin og diagnostik. Billige elektrokemiske plastiksensorer til grundforskning, diagnostik af virusinfektioner og opdagelse af nye lægemidler blev udviklet og evalueret i dette ph.d. projekt. Med en udviklet biosensor chip kunne tidlige tegn på virusinfektion måles elektrisk i cellekultur. Systemet registrerede en infektion i humane celler indenfor et par timer. Dette er en betydelig tidsbesparelse i forhold til traditionel viruskultur, som stadig er den gyldne standard i laboratoriet til diagnosticering af virusinfektioner. Biosensorplatformen blev tilpasset til selektivt at fiske intakte viruspartikler fra kropsvæske ved hjælp af overfladefunktionalisering med aptamerer. Viruspartiklerne bandt til aptamer prober, der var immobiliserede på ledende polymerelektroder, og interaktionen kunne hurtigt og let måles elektrisk. Sensoren svarede hurtigt og udviste høj sensitivitet og specificitet. Klinisk relevante koncentrationer af influenzavirus i spytprøver blev påvist indenfor femten minutter. Apparatet kan potentielt udformes til et omkostningseffektivt diagnostisk point of care system til brug i felten - et sted hvor de fleste etablerede teknikker fejler. Mikrofluide cellemigrationsplatforme - der imiterer in vivo forhold - blev udviklet med succes. De kan forbedre den eksperimentelle in vitro forsøgsopsætning til grundforskning og opdagelse af nye lægemidler. Plastic biosensorer har nået et nyt niveau og medicinsk diagnostik kan drage fordel af integrering af elektriske sensorer i billige plastik mikrosystemer til påvisning af patogener, og bane vejen for point of care undersøgelser. De præsenterede platforme kan potentielt masseproduceres og let tilpasses andre opgaver indenfor området. ; New and emerging infectious diseases pose a growing global challenge for patient diagnosis and treatment, and for public health responses. Biosensors are one of the fastest growing technologies for in vitro diagnostics, and the sophisticated microsystems offer exciting opportunities for decentralized clinical applications in medicine and diagnostics. In this PhD project, low cost electrochemical plastic sensors for basic research, diagnosis of viral infections or drug discovery were developed and evaluated. In the developed biosensor chip, early signs of virus infection in cell culture could be detected electrically using a cell based biosensing platform. The system responded for the infection of human cells within a few hours. This is a highly competitive time frame compared to viral culture, which is still the golden standard for laboratory diagnosis of viral infections. The biosensing platform was adapted to selectively fish out virions from body fluid by aptamer functionalization. The intact virus particles were captured by immobilized aptamer probes on conductive polymer electrodes, allowing fast and easy electrical detection. The sensor responded rapidly, and showed high sensitivity and specificity. Influenza virus in saliva specimen was detectable within fifteen minutes at a clinically relevant concentration. The device has potential for miniaturization into a cost effective field ready point of care diagnostic system, where the majority of established techniques fail to function outside the specialized laboratory. Microfluidic cell migration devices, imitating in vivo conditions were developed with success, improving the in vitro experimental setup for basic research and drug discovery. Polymer biosensors have reached a new level of maturity, and pathogen detection could benefit from the integration of electrical sensors into low cost plastic microdevices pioneering point of care testing. The presented biosensing platforms have potential for scaling up towards high throughput screening, and are adaptable to other applications in medicine and diagnostics, and other fields.