Towards an All-Polymer Biosensor for Early Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is quickly evolving into one of the biggest and most costly health issues in Europe and the United States. AD is a protein misfolding disease, caused by accumulation of abnormally folded β-amyloid and tau protein in the brain. The build-up of protein is believed to degenerate the brain tissue literally shrinking the brain. This slowly destroys function of these parts of the brain. It has been discovered that the concentration of A42 in cerebrospinal fluid (CSF) is a biomarker for this disease. It is therefor of great interest to develop quick and low cost methods for measuring this. Lab-on-a-chip biosensors are one of the fastest growing technologies for in vitro diagnostics. The combination of microfluidics and biosensing offers exciting possibilities for producing extremely sensitive and low cost applications for medicine and diagnostics.This thesis include studies on self-assembly of peptide structures. An investigation into the fibrillation of Aβ42 was conducted with the purpose of using in vitro formed fibrils for pre-concentrating Aβ42. Diphenylalanine (phe-phe) has previously been described as the key recognition motif of the amyloid fibrillation. This thesis also presents a thorough study of the physical and chemical properties of self-assembled Tert-butoxycarbonyl-Phe-Phe-OH peptide structures.Conductive polymer nanowires has recently been suggested as an alterneative to silicon nanowire. In this work we have demonstrated a rapid fabrication of polymerized p-toluenesulfonate doped poly(3,4-ethylenedioxythiophene) (PEDOT:TsO) nanowires. The PEDOT:TsO nanowires are demonstrated to be promising temperature sensors. We also show that the nanowires can be gated with a backgating potential, which is a requirement for using it as a biosensor. The nanowires were also shown to be able to measure changes in larger biological samples as cells. This shows a promise for utilizing the PEDOT:TsOnanowires as Aβ42 biosensors.A prototype for a lab-on-a-chip system consisting of a double assay sorting channel and a electrochemical impedance spectroscopy coulter counter were developed. It was shown that the coulter counter could measure a polystyrene bead concentration with 97% accuracy.<br/