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30. 25. -32.40. 20. Sedimentation. -32.45. Amplitude in dB. 15. Adhesion. -32.50. 10. Magnitude (dB). Spreading. -32.55. 5. -32.60. 0. 0. 50. 100. 150. 200. 250. 300. -32.65. Time in Minutes. 50. 60. 0. 10. 20. 30. 40. Time (min).
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30 25 -32.40 20 Sedimentation -32.45 Amplitude in dB 15 Adhesion -32.50 10 Magnitude (dB) Spreading -32.55 5 -32.60 0 0 50 100 150 200 250 300 -32.65 Time in Minutes 50 60 0 10 20 30 40 Time (min) Sedimentation, adhesion, and proliferation of endothelial cell proliferation Deposition of super collagen on the gold surface in 0.1 mol of HCl solution Spreading of Endothelial Cell NANOBIOSENSOR RESEARCH P R O G R A M O V E R V I E W The Challenges • 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. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
100 MHz 1 GHz 10 MHz Piezo-Bio-Array PNBS Frequency 1 MHz 100 MHz 1 GHz 980 nm 98 nm 28 nm PNBS Frequency 500 MHz Penetration Depth 37 nm Shear-Mode Piezo-Biosensor (Fundamental) Shear-Mode Piezo-Biosensor (Harmonics) NANOBIOSENSOR RESEARCH P R O G R A M O V E R V I E W Development of Piezoelectric NanoBiosensor Technology Platform • 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. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
Portable Measurement System Oscillator, Phase Lock Loop System Vector Voltmeter System Time Domain Analyzer Impedance Meter Network Analyzer Signal Signal Magnitude Display Receiver Generator Phase Display Data Acquisition Signal Processing and Control Computer Control - antibody Liquid - antigen Flow System Liquid Chamber Liquid Chamber Temperature Piezoelectric Crystal Piezoelectric Crystal Measurement Electronic Electronic Compartment Compartment Signal In Signal Out Signal Out Measurement Cell (T, RH,C0 , pH, etc.) 2 2 0.00E+00 0.00E+00 -1.00E+01 -1.00E+01 -2.00E+01 -2.00E+01 -3.00E+01 -3.00E+01 -4.00E+01 -4.00E+01 -5.00E+01 -5.00E+01 -6.00E+01 -6.00E+01 -7.00E+01 -7.00E+01 -8.00E+01 -8.00E+01 4.97E+06 4.97E+06 4.98E+06 4.98E+06 4.99E+06 4.99E+06 5.00E+06 5.00E+06 5.01E+06 5.01E+06 5.02E+06 5.02E+06 5.03E+06 5.03E+06 5.04E+06 5.04E+06 1.00E+02 1.00E+02 8.00E+01 8.00E+01 6.00E+01 6.00E+01 4.00E+01 4.00E+01 Integrated laboratory system for testing and calibration of piezoelectric biosensors. 2.00E+01 2.00E+01 0.00E+00 0.00E+00 4.97E+06 4.97E+06 4.98E+06 4.98E+06 4.99E+06 4.99E+06 5.00E+06 5.00E+06 5.01E+06 5.01E+06 5.02E+06 5.02E+06 5.03E+06 5.03E+06 5.04E+06 5.04E+06 -2.00E+01 -2.00E+01 -4.00E+01 -4.00E+01 -6.00E+01 -6.00E+01 -8.00E+01 -8.00E+01 -1.00E+02 -1.00E+02 -1.20E+02 -1.20E+02 NANOBIOSENSOR RESEARCH P R O G R A M O V E R V I E W Novel Applications of Piezoelectric NanoBiosensor Technology • 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. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
100 MHz 1 GHz 10 MHz Fig. 1 - PINBS operating at the fundamental frequency Fig. 4 - A PINBS Biochip Fig. 3 - Probing depth of the PNBS as a function of frequency Fig. 2 - PINBS operating at the harmonic frequencies A NOVEL PIEZOELECTRIC MICROARRAY BIOSENSOR: LABORATORY-ON-A-CHIP P R O J E C T O V E R V I E W Piezoelectric Interfacial NanoBioSensor (PINBS) - I 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. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
PLAGA Nanofiber-based Biosesnor Interface Endothelial Cell on PLAGA Nanofiber Interface( initial stage) and after 2 hours ( nicely spread). NOVEL INTERFACES FOR PIEZOELECTRIC INTERFACIAL NANOBIOSENSORS P R O J E C T O V E R V I E W Piezoelectric Interfacial NanoBioSensor (PINBS) - II This research is focused for development of artificial nanofiber-based interfaces for cell-based functional biosensors. The PINBS response To the nanofiber loading. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
High Frequency Excitation Piezoelectric Sensor Piezoelectric Sensor Piezoelectric Sensor Nano-Microparticle-Cell m – mass k – effective elasticity representing interfacial bonding energy r – dissipative losses k r Nano-Microparticle-Cell on the surface of the sensor Piezoelectric Sensor: M – mass k – elasticity r – dissipative losses Piezoelectric Sensor R Equivalent Electromechanical System Amplitude f Reference Sensor Response Sensor Response with a Nanoparticle 10.00000 10.10000 Frequency (MHz) PIEZOELECTRIC BIOSENSOR FOR MONITORING INTERACTION OF A SINGLE PARTICLE & CELL WITH SOLID SURFACES: ENDOTHELIAL CELL ON A GOLD SURFACE P R O J E C T O V E R V I E W Micro-nano Particle Size Distribution Sensor 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. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
PINBS FOR MONITORING INTERFACIAL PROCESSES INVOLVING CELLS AND VARIOUS SURFACES P R O J E C T O V E R V I E W Endothelial Cell Properties Such As Sedimentation, Adhesion, Proliferation, and Fixation Sedimentation, adhesion and proliferation profile of endothelial cells as a function of time measured using 25 MHz piezoelectric resonant sensor. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu
Deposition of Collagen on the gold surface (50ul of Collagen in 0.1mol of Hcl) Frequency Response at Fundamental Frequency 10.015 10.01 10.005 10 9.995 9.99 Frequency in MHz 9.985 9.98 9.975 9.97 PNBS Frequency 10 MHz Probing Depth 178 nm 0 50 100 150 200 250 300 Decay of Acoustic Shear Wave (Envelope) y Time in Minutes x Displacement Deposition of Collagen on the gold surface (50ul of Collagen in 0.1mol of Hcl) Electrode Excitation Voltage Piezoelectric Quartz Phase Variation at Fundamental Frequency Electrode Solid/Liquid Interface (Boundary Conditions) 100 80 60 Phase in Degree 40 20 0 0 50 100 150 200 250 300 Time in Minutes MONITORING THE KINETICS OF THIN BIOLOGICAL FILM FORMATION IN REAL TIME P R O J E C T O V E R V I E W Phase Transitions of Thin Biological Films The purpose of this project is the development of a sensitive technique for measuring phase transitions of thin biological films. • Faculty:Ryszard M. Lec, PhD, Drexel University. • E-mail: r.lec@coe.drexel.edu