1. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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 0 5 10 15 20 25 30 050100150200250300 Time in Minutes Amplitude in dB -32.65 -32.60 -32.55 -32.50 -32.45 -32.40 010203040 5060 Time (min) Sedimentation Adhesion Spreading Magnitude (dB) Faculty: Ryszard M. Lec, PhD, Drexel University. E-mail: r.lec@coe.drexel.edu Spreading of Endothelial Cell

2. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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. E-mail: r.lec@coe.drexel.edu

3. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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+02 -1.00E+02 -8.00E+01 -6.00E+01 -4.00E+01 -2.00E+01 0.00E+00 2.00E+01 4.00E+01 6.00E+01 8.00E+01 1.00E+02 4.97E+064.98E+064.99E+065.00E+065.01E+065.02E+065.03E+065.04E+06 -8.00E+01 -7.00E+01 -6.00E+01 -5.00E+01 -4.00E+01 -3.00E+01 -2.00E+01 -1.00E+01 0.00E+00 4.97E+064.98E+064.99E+065.00E+065.01E+065.02E+065.03E+065.04E+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+02 -1.00E+02 -8.00E+01 -6.00E+01 -4.00E+01 -2.00E+01 0.00E+00 2.00E+01 4.00E+01 6.00E+01 8.00E+01 1.00E+02 4.97E+064.98E+064.99E+065.00E+065.01E+065.02E+065.03E+065.04E+06 -8.00E+01 -7.00E+01 -6.00E+01 -5.00E+01 -4.00E+01 -3.00E+01 -2.00E+01 -1.00E+01 0.00E+00 4.97E+064.98E+064.99E+065.00E+065.01E+065.02E+065.03E+065.04E+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. E-mail: r.lec@coe.drexel.edu

4. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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. E-mail: r.lec@coe.drexel.edu

5. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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. E-mail: r.lec@coe.drexel.edu

6. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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 10.00000 Amplitude 10.10000 Frequency (MHz) Sensor Response with a Nanoparticle Reference Sensor Response Micro-nano Particle Size Distribution Sensor PROJECTOVERVIEWPROJECTOVERVIEW Faculty: Ryszard M. Lec, PhD, Drexel University. E-mail: r.lec@coe.drexel.edu

7. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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. E-mail: r.lec@coe.drexel.edu

8. School of Biomedical Engineering, Science & Health Systems WWW.BIOMED.DREXEL.EDU 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. E-mail: r.lec@coe.drexel.edu