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1.Overview Our group is focused on development of electronic sensors for sensitive, rapid, low cost and on-site applicable detection of diseases/illness. These devices that are based on electrochemical and electromagnetic signal detection are currently under investigation using bio-affinity reagents such as Antibodies, Aptamers and recombinant proteins. Electrochemical devices have shown a dynamic detection range spanning 6-7 orders of target analyte concentrations, in general ranging from 0.01ng/mL to 10ug/mL based on the target molecules. On the other hand the electromagnetic sensor has shown a dynamic detection range spanning 8-9 orders of applied magnetic field, thus these sensors are expected to be much more sensitive as compared to electrochemical devices, where non-specific signal limits the sensitivity to around low ng/mL range 1-2. 5.Electromagnetic Biosensor platform 2.Electrochemical Biosensor platform Electrochemical biosensing is based on the perturbation of charge transfer dynamics at the surface of the metal electrode by the bioactive layer and the observed impedance change can be correlated with biomolecular activity. Electrochemical Impedance Spectroscopy can be used to monitor both fast events (electron transfer) at high frequencies and slow events (biomolecular diffusion) at low frequencies 1. PrA Immobilized Binding with IgG Regeneration Native e-e- e-e- + - L G W W G H -ve +ve X Y Distance from electrode C dl R ct ZwZw Electrode R sol Z (imaginary) Z (Real) Diffusion Layer Double Layer Bulk Solution R sol R sol + R ct Mass transfer control Electron transfer control Decreasing Frequency Fig. 1 shows the typical layout and geometrical parameters for IDEs Randles equivalent electrical circuit (REEC) can be related to the interfacial EIS parameters and the experimental data using Nyquists plots. The electrodes are sensitive to the electrochemical environment (redox probe). The biomolecular layer impedes the electron flow between the electrode and ions in solution and is observable by change in diameter of semicircular portion of the Nyquists Plot and quantifiable by fitting data in a Randles circuit Electromagnetic biosensing is based on magnetoresistance i.e., change in resistance of a material in response to a small externally applied electromagnetic field. This effect is significant in some multilayer systems where a large change in resistance of up to 80% have been reported 3-4. This phenomenon, which is based upon the quantum mechanical exchange coupling between nm thin layers of magnetic materials (Fe/Co/Ni) that are separated by comparably thin layers of nonmagnetic materials (Cu), is known as giant magnetoresistance (GMR) 3-4. TargetApplication areaDetection RangeSensitivity (IC50) C-Reactive Protein 1 Cardiovascular 1 100pg-1ug/mL4.82ng/mL AntiTG-Abs 2 Gluten Allergy 2 10pg-10ug/mL35.6ng/mL Ryaonidine Receptor - Fk506 Muscular (drug-protein) (Ca++ channel) 0.01-100nM15.86nM HE4Ovarian Cancer1-100ng/mL5.03ng/mL Atrazine / 2,4-DPesticides/Environment0.05ppb-500ppbTo be determined 3.Electrochemical Device status 6.Electromagnetic Device status G/W/H=480/1522/200nm Fig. 2 IDEs were designed for different combinations of gap (G), width (W) and height (H) of the electrode digits the length (L) was considered constant and >> G/W/H. It was observed that device sensitivity increased significantly with G < 800nm (Singh et al. 2010). Optimized IDE design with G=500nm, H=200nm, W=1500nm and L=180um arranged in an 8 electrodes linear array in a SD card format with a microfluidic chamber determined on top of the electrodes. The graph shows results of gluten allergy biomarker using IDEA chip and EIS as detection technique. Fig_4 A 15 electrode (3X5) GMR sensor chip designed in XD card format. Initial Measurement setup showing external magnetic coils for horizontal biasing and magnetization of bound NPs. AFM of surface bound PrA-NPs on IgG functionalized chip. A graph showing relative change in impedance of GMR chip functionalized with IgG Abs upon binding of PrA-MNPs at different dilutions 0, 10 and 100x 4.Target applications 7.Biosensor systems Table 1: Performance of some of the biosensors that we have developed. Substrate +ve-ve Substrate +ve -ve NS NSNS Fig 3a. The magnetic microdomains are pinned unidirectionally during fabrication Fig 3b. MNPs cause microdomain reorientation and change the electrical signal Fig 3c. The GMR sensor is affected by horizontal component of externally applied electromagnetic field Fig 3d. The GMR sensor signal is proportional to the externally applied Horizontal magnetic field Blood Separation Matrix(removes large cells/RBCs) Plasma filtration Matrix NP-label Conjugate Release Matrix Waste/ Overflow GMR sensor Blood (5-50ul) Buffer/reagents (20- 100ul) + Control Ab Test Ab Fig 5. Schematic showing the components of a GMR biochip IDEA electrochemical biosensor platform capable of detection in the 1ng-10ug/mL. High non-specific signal at low concentrations (