School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] NANOBIOSENSOR RESEARCH The Challenges PROGRAM OVERVIEWPROGRAM OVERVIEW Attain a fundamental understanding of nanoscale biosensing phenomena. Design and fabricate biologically active sensing interfaces: DNA, proteins, cells, tissues, other. Design and fabricate solid-state based transducer structures capable of simultaneous detection of multiple biological substances and processes: biosensor chips, biosensor arrays, other. Novel theoretical and experimental tools for a rapid development of the NanoBiosensor technology. Integration of biological, physical (mechanical, optical, acoustic) and electronic components into multifunctional biosensor systems: novel immobilization techniques; solid-state transducer nano/microfabrication technologies; microfluidic systems; IC circuits for signal conditioning and processing; smart biosensors and biosensor systems. Sedimentation, adhesion, and proliferation of endothelial cell proliferation Deposition of super collagen on the gold surface in 0.1 mol of HCl solution Time in Minutes Amplitude in dB Time (min) Sedimentation Adhesion Spreading Magnitude (dB) Faculty: Ryszard M. Lec, PhD, Drexel University. Spreading of Endothelial Cell

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] NANOBIOSENSOR RESEARCH Development of Piezoelectric NanoBiosensor Technology Platform PROGRAM OVERVIEWPROGRAM OVERVIEW Important Features: Multidomain Piezoelectric Sensing Mechanisms: mass, viscosity, elasticity, electric conductivity, and dielectric constants. Real-time Piezoelectric Monitoring of Interfacial Biological Phenomena: the depth of monitoring ranges from a single to hundreds nanometers with the time resolution of milliseconds. Piezoelectric Biotransducer Technology: IC compatible, MEMS/NEMS; sensing and actuating; multiple-sensing- wave transducers, piezo-bio-chips and arrays, other. Bio-Piezo-Interfaces: design and synthesis of surfaces at the atomic level to produce sensing interfaces with desired properties and functions. Integrated Electronic Signal Processing and Display Technologies: fast, miniature, inexpensive, reliable. Smart Biosensors: self-calibration, self-diagnostic, self-repair, other. 10 MHz 100 MHz 1 GHz Piezo-Bio-Array PNBS Frequency 1 MHz 100 MHz 1 GHz PNBS Frequency 500 MHz 980 nm 98 nm 28 nm Penetration Depth 37 nm Shear-Mode Piezo-Biosensor (Fundamental)Shear-Mode Piezo-Biosensor (Harmonics) Faculty: Ryszard M. Lec, PhD, Drexel University.

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] NANOBIOSENSOR RESEARCH Novel Applications of Piezoelectric NanoBiosensor Technology PROGRAM OVERVIEWPROGRAM OVERVIEW DNA sensors/chips: genetic screening and diseases, drug testing, environmental monitoring, biowarfare, bioterrorism, other. Immunosensors: HIV, hepatitis, other viral diseases, drug testing, environmental monitoring, biowarfare, bioterrorism, other. Cell-based sensors: functional sensors, drug testing, environmental monitoring, biowarfare, bioterrorism, other. Point-of-care sensors: blood, urine, electrolytes, gases, steroids, drugs, hormones, proteins, other. Bacteria sensors (E-coli, streptococcus, other): food industry, medicine, environmental, other. Enzyme sensors: diabetics, drug testing, other. Market: clinical diagnostic, environmental monitoring, biotechnology, pharmaceutical industry, food analysis, cosmetic industry, other. – Immunosensors: about 1 billion annually. – DNA probes: about 1.5 billion annually. Vector Voltmeter System Impedance Meter Time Domain Analyzer Control SignalProcessing Data Acquisition and Control Computer Magnitude Display Phase Display Signal Receiver -1.20E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E+06 Portable Measurement System Oscillator, Phase Lock Loop System (T, RH,C0 2, pH, etc.) Measurement Signal Out Liquid Chamber Piezoelectric Crystal Electronic Compartment Liquid Flow System Signal Generator Network Analyzer -1.20E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E+06 Measurement Cell 2 Temperature Signal InSignal Out Liquid Chamber Piezoelectric Crystal Electronic Compartment - antigen - antibody Integrated laboratory system for testing and calibration of piezoelectric biosensors. Faculty: Ryszard M. Lec, PhD, Drexel University.

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] A NOVEL PIEZOELECTRIC MICROARRAY BIOSENSOR: LABORATORY-ON-A-CHIP Piezoelectric Interfacial NanoBioSensor (PINBS) technology offers a unique opportunity to develop a biochip in which both sensing and actuating (mixing, flowing, etc. ) are implemented using the same technology platform. Fig. 1 - PINBS operating at the fundamental frequency Fig. 3 - Probing depth of the PNBS as a function of frequency Fig. 2 - PINBS operating at the harmonic frequencies 10 MHz 100 MHz 1 GHz Fig. 4 - A PINBS Biochip Piezoelectric Interfacial NanoBioSensor (PINBS) - I PROJECTOVERVIEWPROJECTOVERVIEW Faculty: Ryszard M. Lec, PhD, Drexel University.

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] NOVEL INTERFACES FOR PIEZOELECTRIC INTERFACIAL NANOBIOSENSORS This research is focused for development of artificial nanofiber-based interfaces for cell-based functional biosensors. PLAGA Nanofiber-based Biosesnor Interface Endothelial Cell on PLAGA Nanofiber Interface( initial stage) and after 2 hours ( nicely spread). Piezoelectric Interfacial NanoBioSensor (PINBS) - II The PINBS response To the nanofiber loading. PROJECTOVERVIEWPROJECTOVERVIEW Faculty: Ryszard M. Lec, PhD, Drexel University.

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] PIEZOELECTRIC BIOSENSOR FOR MONITORING INTERACTION OF A SINGLE PARTICLE & CELL WITH SOLID SURFACES: ENDOTHELIAL CELL ON A GOLD SURFACE The objective of this project is to develop a technique for measuring particle size and binding energy between a particle (cell) and the solid interface. Piezoelectric Sensor High Frequency Excitation k r R Equivalent Electromechanical System Nano-Microparticle-Cell m – mass k – effective elasticity representing interfacial bonding energy r – dissipative losses Piezoelectric Sensor: M – mass k – elasticity r – dissipative losses Piezoelectric Sensor Nano-Microparticle-Cell on the surface of the sensor ff Amplitude Frequency (MHz) Sensor Response with a Nanoparticle Reference Sensor Response Micro-nano Particle Size Distribution Sensor PROJECTOVERVIEWPROJECTOVERVIEW Faculty: Ryszard M. Lec, PhD, Drexel University.

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] PINBS FOR MONITORING INTERFACIAL PROCESSES INVOLVING CELLS AND VARIOUS SURFACES Sedimentation, adhesion and proliferation profile of endothelial cells as a function of time measured using 25 MHz piezoelectric resonant sensor. Endothelial Cell Properties Such As Sedimentation, Adhesion, Proliferation, and Fixation PROJECTOVERVIEWPROJECTOVERVIEW Faculty: Ryszard M. Lec, PhD, Drexel University.

School of Biomedical Engineering, Science & Health Systems V 1.0 SD [030814] MONITORING THE KINETICS OF THIN BIOLOGICAL FILM FORMATION IN REAL TIME Electrode Piezoelectric Quartz x y Electrode Excitation Voltage PNBS Frequency 10 MHz Probing Depth 178 nm Decay of Acoustic Shear Wave (Envelope) Displacement Solid/Liquid Interface (Boundary Conditions) The purpose of this project is the development of a sensitive technique for measuring phase transitions of thin biological films. Phase Transitions of Thin Biological Films PROJECTOVERVIEWPROJECTOVERVIEW Faculty: Ryszard M. Lec, PhD, Drexel University.