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Lecture 16: Biosensors

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Lecture 16: Biosensors Lecture 16: Biosensors 498Bio: Introduction to Biophysics MOS Capacitor p = NA in neutral bulk - + Threshold voltage: the volume density of electrons in the inversion layer is the same as the volume density of holes in the body MOSFET OFF ON Modes of operation Cut-off or Sub-threshold V GS < Vth: Limited by carriers Linear Region: VGS > Vth and VDS < ( VGS - Vth) Limited by VDS Saturation Mode, VGS > Vth and VDS > ( VGS - Vth) ) Limited by carriers (pinch-off near the drain) Field-effect gating of ionic current Nanotubes are 40–50 nm in inner diameter and 15 µm in length PRL 95:086607 gate voltage Vg shifts the distribution of the electrostatic potential in a nanotube Doping: p-type n-type Protein transistor Neutral surface, charged protein 30nm gap in transistor Avidin (positive charge) [avidin] = 30µM [KCl] 10µM λD=30-100nm Gate potential modulates diffusion Protein transistor 1V (off) 1V (off) -1V (on) -1V across the channel; Modulate potential of the left gate, keep the right gate at 0 Applied Physics Letters 88, 123114 Ion-Sensitive Field Effect Transistor pH sensor Sufficiently positive bias induces an n-type inversion layer in the channel between source and drain. Upper layer of the gate Insulator can bind specific analytes The drain current is determined by the effective electrical resistance of the surface inversion layer and the voltage between source and drain EnFET ImmunoFET Requires very low salt concentrations Measures surface charge Dynamics measurements changing ion concentration Bio FEDs Capacitive EIS (electrolyte- insulator-semiconductor) sensor Bio FEDs Light-Addressable Potentiometric Sensor By sweeping the applied voltage, inversion to accumulation transition happens at the semiconductor Inversion surface Accumulation Cell/FET hybrids “Glucose sensor” Metabolic activity changes pH Neurons on chips Action potential modulates source-drain current Small 1 (2005) 206-210 Label-free detection of DNA hybridization Hybridization effectively modulates the charge applied to the gate Alters capacitance, threshold voltage source-drain current Questions: Why less DNA gives more signal? How can it work without the reference electrode? Electroanalysis 18:1893 Taste Sensor Sourness: H+of HCl, acetic acid, citric acid and so on; Saltiness: NaCl; Bitterness: quinine, caffeine, L-tryptophan and MgCl2; Sweetness: sucrose, fructose, glucose, L-alanine and so on; Umami (Japanese for deliciousness’): monosodium glutamate (MSG) in seaweeds, disodium inosinate (IMP) in meat and fish and disodium guanylate (GMP) in mushrooms. Meas. Sci. Technol. 9 (1998) 1919–1936. Taste Sensor Taste-sensing FET (TSFET) Does is work? Coffee Beer “Carbon dioxide in the standard beer was removed by stirring it for one night” Sake Miso Simple physical model of FET sensor Nanowires Further examples Electronic Detection of Biopolymers PRE 70, 031906 ID = f(USD, US) Fix point measurement: keep ID, USD constant by varying US Theoretical model Nanowires Charles M. Lieber, Harvard U. Nanowire electronics Making nanowires Produced using metal clusters as catalysts via a vapour-liquid-solid process from an eutectic mixture Can be only 3 nm in diameter High aspect ratio 5 nm J. Phys. D: 39:R387 Heterogeneous nanowires A change in the reactant leads to either (c) axial heterostructure growth or (d) radial heterostructure growth Nanowire FET Top gated FET Source and drain are metal Assembly Langmuir-Blodgett assembly Fluidic flow-directed assembly The pattern depends on the flow Uniaxially compress NW-surfactant Monolayer (aqueous subphase) Nanowires can be used as bioFET Nanomedicine 1:51 What is so great? They are 1D! No label, electronic read out, watch as it binds Drug design Electronically monitor competitive binding of a drug Chronic leukemia drug PNAS 102:3208 Does it work? 500 nm 0.1 3 20 nM ATP Gleevec is less charged than ATP Electronic detection of DNA M W Goal: Distinguish F508 mutation (cystic fibrosis) Nano Lett. 4:51 Protein detection antibodies p-type n-type 0.9, 0.9, 0.009, 0.0009, 5 ng/ml Nat. Biotech. 23:1294 Prostate specific antigen (PCA) Protein detection PSA CEA mucin-1 1: 0.9 ng/ml PSA 2: 1.4 pg/ml PSA Multiplex, real-time, label-free 3: 0.2 ng/ml CEA marker protein detection 4: 2 pg/ml CEA 5: 0.5 ng/ml mucin-1 Femtomolar sensitivity 6: 5 pg/ml mucin-1 Compete selectivity Nat. Biotech. 23:1294 Electrical detection of viruses PNAS 101:14018 Carbon Nanotubes ChemPhysChem 5:1084 Fullerene Discovery: 1985 Water soluble fullerene C60 Kroto, Curl, and Smalley were awarded the 1996 Nobel Prize in Chemistry Fundamentals Rolling up a (10,10) nanotube armchair zigzag chiral (10,10) (15,0) (12,7) z Ch Shigeo Maruyama, University of Tokyo r =na+mb Metallic: n-m=3p, where p is integer Semiconductor: all other Band gap is proportional to the diameter a roll-up vector r and a chiral angle θ Multiwall CWNT A) SWCNTs with a triangular cross- section fabricated in a porous alumina template B) SEM images of the a carbon bulb and flask (by means of explosion) Synthesis Techniques: Arc discharge between graphite electrodes the method first nanotubes were produced (1991) Laser abilation (vaporize graphite with a laser pulse) produces primarily single-walled carbon nanotubes Chemical vapor deposition (really long tubes) Wendy Beckman, U of Cincinnati Use for electronics STM image of band structure Electrical conductivity up to a 1000 times greater than copper Cees Dekker, Delft Kink junction (metal-semiconductor). Acts as a molecular nonlinear diod Nanotube transistor Nanotube is bucked as a straw Nano-RAM (NRAM) Nanotube is pulled into ON state by an electric field Van der Waals interactions are sufficient to stabilize the the ON state Reverse potential switches the state back to OFF Functionalizing CNT Covalent noncovalent hybrid More in Nanotechnology 18:412001 Field-effect immuno-sensor presence absence Cees Dekker Biological Applications as Biosensors Biological systems are known to be highly transparent to 700- to 1,100-nm near-infrared (NIR) light. Change in the emission spectra indicates DNA damage produced by interaction with melphalan (chemotherapeutic agent) Courtesy of the Strano group Gene delivery + plasmid DNA = vaccination Intracellular protein transport 1. Nonspecific adsorption of proteins to SWCN 2. Transport through cell wall via endocytosis: i. uptake ii. break away from endosomes 3. Release using chloroquine cytochrom-c induced apoptosis JACS 127:6021 Nanobombs (new cancer treatment) folate moiety is for selective internalization by tumor cells 5 x 2 minute pulses kill cancerous cells normal cells live Toxicity ?.
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