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Microfluidic devices for biomolecular and cellular analysis

by Ari Hokkanen

Institution: Aalto University
Year: 2016
Posted: 02/05/2017
Record ID: 2071684
Full text PDF: https://aaltodoc.aalto.fi/handle/123456789/19856


Abstract

In this thesis microfluidic chips were developed for tissue sampling, chemical separation and electrical cell stimulation. Several fluorescence measurement systems were developed in order to enable small volume measurements in microchannels.  Microneedle sampling was developed for cancer tissue analysis. A novel two channel silicon microneedle structure was designed and fabricated. Silicon chip was glue bonded to polymer microfluidic part, which had microfluidic channels as fluid reservoirs and actuation membranes for a fluidic control. Phosphatidylcholine (PC) and phosphoethanolamine (PE) lipids were successfully extracted as biomarkers for breast cancer.  Microchip capillary electrophoresis (CE) was shown on silicon-glass chip, which had integrated thin film electrodes for high voltages (HV). This silicon-glass microchip was used for testosterone measurements with LIF detection. Another CE chip was made by hot embossing PMMA (polymethyl methacrylate). It was used to an antibiotic resistance measurement with mecA gene. Confocal four-colour laser induced fluorescence detection system was developed for roll-to-roll hot embossed PMMA chip.  Glass chip was developed for human embryonic stem cells stimulation. Titanium thin film electrodes were deposited on glass surface. The native beat cycle of embryonic stem cells could be altered from about 1 s to 800 ms with electrical stimulation.  Microfluidics makes fast healthcare analysis possible in doctor's office or even in home without time-consuming laboratory analysis. Treatment and medication could be started immediately without delay also avoiding unnecessary medication. Microfluidic devices require small sample amounts and low reagent consumption, which can lower cost of diagnosis; and tightly localized diagnosis and treatment, even at single cell level, enabling novel treatments. This is expected to bring major savings for healthcare system in future.; Tässä väistöstyössä kehitettiin syöpäkudosleikkeiden analysointiin mikroneulanäytteenottoa, johon suunniteltiin ja valmistettiin uusi kaksikanavainen piimikroneula. Mikroneulanäytteen nestesäiliöksi ja fluidistiikan hallintaan kehitettiin polymeerikanavisto, johon piimikroneula liitettiin liimaamalla. Mikroneulanäytteenoton toimivuus osoitettiin uuttamalla phosphatidylcholine (PC) ja phosphoethanolamine (PE) lipidejä, jotka toimivat biomarkkereina rintasyövälle.  Kapillaarielektroforeesiin perustuvaan molekyylien erotuksen kehitettiin pii-lasimikrokanavisto, jolle kasvatettiin amorfisesta piistä elektrodit sähkökentälle. Tätä pii-lasimikrokanavistoa käytettiin testosteronimittauksiin. Kapillaarielektroforeesiin kehitettiin myös kuumapuristettu polymethyl methacrylate (PMMA) kanavisto antibioottiresistanssin mittaamiseen mecA geenin avulla. Tälle PMMA kanavistolle rakennettiin fluoresenssimittaussysteemi, jossa käytettiin laseriin perustuvaa fluoresenssiviritystä ja konfokaalista nelivärimittausta.  Lisäksi väitöstyössä kasvatettiin lasialustalle titaanielektrodeja, joita käytettiin sydänkantasolujen… Advisors/Committee Members: Franssila, Sami, Prof., Aalto University, Department of Materials Science and Engineering, Finland (advisor).

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