CAREER: A Probe-less Large-Array Protein Sensor via MEMS Technology

Miniaturized protein sensors can be used for many applications where macro-sized instruments cannot reach, such as in medical implants, unmanned or unattended environment monitoring, and point-of-care health monitoring units. Despite their extensive development, diagnostic and prognostic approaches using miniaturized protein sensors have severe limitations partially because the specificity and selectivity of the sensor is completely dependent on molecular probes attached to a transducer. To address these limitations, the objective of this CAREER proposal is to study the competitive nature of protein adsorption/desorption and form a probe-less large-array protein sensor via MEMS (Micro-Electro-Mechanical-Systems) technology, aimed at highly-selective and sensitive protein detection up to a concentration of 0.039 ng/mL. Intellectual Merit: Existing MEMS-based biosensors that use a variety of transduction mechanisms have extremely high sensitivity. To achieve high selectivity, however, they use molecular probes (bio-receptors) such as nucleic acids, enzymes, immunoagents, and antibodies and are attached to transducer surfaces to capture specific target molecules. However, these probes impose many limitations: time-consuming complex preparation, sophisticated attachment protocols, expensive reagents, highly-educated technicians to operate, and above all it is impossible to find probes for all target molecules. The proposed research tackles these fundamental issues by leveraging natures competitive adsorption/desorption phenomena, namely the Vroman effect. This competitive nature of protein adsorption/desorption allows highly-selective and sensitive biosensors. By having a large array of different surfaces that are covered by proteins of known size, it is possible to have a miniaturized protein sensor without using molecular probes via MEMS technology. The proposed sensor is characterized by SPR (Surface Plasmon Resonance) and eventually interfaced with a high-Q FBAR (Film Bulk Acoustic Resonator) using integrated microfluidic channels. According to the performance analysis, it is possible to measure 0.039 ng/mL protein concentration, which is suitable to detect many regulatory proteins and bio-markers for various pathogens. The MEMS-based protein sensor is designed to be robust and field-deployable and to operate at wide temperature ranges without losing performance as a result of its unique wafer-level packaging technology. This packaging technology accommodates both electrical and fluidic feedthroughs from the bottom of the substrate, uses novel polymers to eliminate troublesome wet release, and is all wafer-level for a cost-effective solution. The MEMS-based protein sensor is evaluated using two target proteins for proof-of-concept of high and low concentration plasma proteins; fibrinogen and CEA (Carcino-embryonic Antigen), which are indicator proteins for cardiovascular diseases and colorectal cancer. Broader Impact: The outcome of the research will have a significant impact on the cost of biosensors through reduced complexity of design, while increasing their portability and, more importantly, enhancing the selectivity of the biosensor for protein detection applications. The proposed probe-less biosensor is a new concept, which can lead to new research areas in instruments for biological research. The generic feature of our micro-packaging methodology can be used for other types of MEMS-based devices. The packaging method will support both electric and fluidic feedthroughs, a desired requirement for lab-on-a-chip systems. The educational activities range from K-12 students and teachers to college students including under-represented minorities and women. Students will experience a quick experiment to understand fundamentals of proteins via the YES! Summer Program through the STEM (Science, Technology, Engineering, and Mathematics) center at ASU (Arizona State University). For sust

This is a request for an REU Supplement on an existing award, A Probe-less Large-array Protein Sensor via MEMS Technology. An ASU (Arizona State University) EE (Electrical Engineering) undergraduate student, Mr. Marco Carrillo, will participate the project to build a PCB design and characterization of the sensor system. He will be supervised by the PI, Junseok Chae.