Biosensors Initiative Collage

1. BiosensorsInitiative Collage Ryszard Lec Professor of Biomedical & Electrical Engineering Drexel University Philadelphia, PA www.biomed.drexel.edu

2. Nano-Biosensor Science, Engineering and Technology: 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 Nano-Biosensor 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. Endothelial Cell Proliferation Sedimentation Adhesion Proliferation Sedimentation, adhesion, and proliferation of Endothelial Cell Proliferation Deposition of super collagen on the gold surface in 0.1 mol of HCl solution

3. PNBS Frequency 1 MHz 100 MHz 1 GHz Nano-Biosensor Science, Engineering and TechnologyObjective: Development of Piezoelectric Nano-Biosensor Technology PlatformImportant Features: 980 nm 98 nm 28 nm PNBS Frequency 500 MHz Penetration Depth 37 nm • 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. Shear-Mode Piezo-Biosensor (Fundamental) Shear-Mode Piezo-Biosensor (Harmonics) 100 MHz 1 GHz 10 MHz Piezo-Bio-Array

4. 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 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 Nano-Biosensor Science, Engineering and TechnologyObjective: Novel Applications of Piezoelectric Nano-Biosensor 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 Integrated Laboratory System for Testing and Calibration of Piezoelectric Biosensors

5. Project Title: Sensing Principles of Piezoelectric Nano-Biochemical Sensors (PNBS) Nano-Biosensor Research Laboratory Michael Francois (Ph.D), Sun Jong Kwoun (MS Student) Advisors: Dr. Ryszard M. Lec, Dr. Kambiz Pourrezaei PNBS Frequency 1 MHz 100 MHz 1 GHz 980 nm 98 nm 28 nm PNBS Frequency 500 MHz 37 nm Fig. 1. PNBS operating at the fundamental frequency Fig. 2. PNBS operating at the harmonic frequencies 100 MHz 10 MHz 1 GHz Penetration Depth [nanometers] Fig. 3. Probing depth of the PNBS as a function of frequency Fig. 4. A PNBS Biochip

6. Project Title: A Novel Polymer Nanofiber Interface for Biochemical Sensor Applications Nano-Biosensor Research Laboratory Sun Jong Kwoun (MS Student) Advisors: Dr. Ryszard M. Lec (Biomed.), Dr. Frank K. Ko (Material Eng. Dept.) Fig. 2. SEM picture of the nanofiber film at 6000X magnifications. Fig. 1. Photograph of the TSM sensor with deposited nanofiber film. Fig. 3. Endothelial cell attached to the nanofiber matrix. NF Sensor Air Fig. 4. The S21 amplitude of the nanofiber deposited sensors in air as a function of frequency for five different deposition time (corresponding to different NF film thickness). Fig. 3. Cell growth on nano fibrous matrix (after 1 day).

7. Project Title: Piezoelectric Biosensor for Monitoring the Interaction of a single cell with solid surfaces: Endothelial Cell on Gold Surface Nano-Biosensor Research Laboratory Qiliang Zhang (Ph.D student) Advisors: Dr. Ryszard M. Lec (Biomed), Dr. Kambiz Pourrezaei (ECE) Nano-Microparticle-Cell on the surface of the sensor High Frequency Excitation Piezoelectric Sensor Piezoelectric Sensor Piezoelectric Sensor Nano-Microparticle-Cell m – mass k – effective elasticity representing interfacial bonding energy r – dissipative losses Amplitude f k r Reference Sensor Response Nano-Microparticle-Cell on the surface of the sensor Sensor Response with a Nanoparticle Piezoelectric Sensor: M – mass k – elasticity r – dissipative losses Piezoelectric Sensor R 10.10000 Frequency (MHz) 10.00000 Equivalent Electromechanical Circuit

8. Nano-Biosensor Research LaboratoryProject Title: Piezoelectric Nano-Biosensor for Monitoring Interfacial Cell Processes: Endothelial Cell Properties such as sedimentation, adhesion, proliferation and fixationStudents: Vadivel Devaraju, (PhD) and Joe Sorial, (MS)Faculty: Dr. Ryszard M. Lec and Dr. Kenneth Barbee Fixation Sedimentation 5MHz Attachment Proliferation Fixation 15MHz Figure 1. (a) Sedimentation, adhesion and proliferation profile of endothelial cells as a function of time measured using 25 MHz piezoelectric resonant sensor + the caption for the second picture

9. PNBS Frequency 10 MHz Probing Depth 178 nm Decay of Acoustic Shear Wave (Envelope) y x Displacement Excitation Voltage Electrode Piezoelectric Quartz Electrode Solid/Liquid Interface (Boundary Conditions) Nano-Biosensor Research LaboratoryProject Title: Piezoelectric Nano-Biosensor for Monitoring Interfacial Protein ProcessesStudent: Vadivel Devaraju, (PhD) Faculty: Dr. Ryszard M. Lec and Dr. Andrew Fertala

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