ADVANCED BIOSENSING FOR MOLECULAR AND CELLULAR BIOMARKERS

目前的医学试验主要是在有条件的实验室中由训练有素的人员进行的，这些人员有稳定的电力和持续的试剂供应。然而，在许多情况下，具有分析点或护理点功能是有价值的。例如，环境因素最好在现场进行评估

Present medical tests are largely performed in conditioned laboratories by highly trained personel with access to stable power and a constant supply of reagents. In many situations, however, it is valuable to have point-of-analysis or point-of-care capabilities. For example, environmental factors may best be evaluated onsite to avoid transportation of samples, to provide a real-time warning, when working in third world countries, or when working in challenging and hostile environments. The long term aim of this project is to develop a paradigm for a fully integrated platform for performing complex protein assays in the field. The system consists of a programmable microfluidic sample processing device called a cellular automaton coupled to a novel Hall-effect electrical sensor. This analysis system will be developed to detect PAH-protein adducts that mutagenic and carcenogenic challenges. However, the development of this general platform for immunodetection of targets will also find wide application in biomedical research, pathogen and infectious disease detection. Our overall goal will be addressed by the following specific aims: 1. A microfluidic automaton will be developed that is a programmable microfluidic device for performing fluidic and sample preparation operations at the nanoliter scale. This device will be developed and tested to perform the operations necessary to do basic optically detected ELISA analyzes of PAH-protein adducts. 2. In parallel, the Boser group will design and fabricate a set of advanced Hall Sensor chips that are optimized for mating with the automaton and detecting the immunoassay process. 3. The next step will demonstrate the integration of the automaton sample preparation with the Hall sensor for the detection of PAH-protein adducts. Once the assays are demonstrated to be compatible, the Hall sensor will be directly coupled with the automaton to form a prototype integrated analysis system. In the final aim a fully integrated electronic interface and low-cost disposable microfluidic cartridges and instrument will be developed to perform sample preprocessing, incubation, mixing with reagents, and detection of the analyte automatically in the cartridge. This project leverages microfluidic sample preparation and state-of-the-art detection with the PAH assay developed in Project 1 of this proposal. These technologies will lead to devices and methods for early detection and better information that will lead to more accurate diagnosis and targeted treatments.