and Chemical Biochemical Microsystems
1. Chemical Sensors 2. Chemical Actuators 3. Bioelectric Devices 4. Example: Electronic Nose
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Generally, chemical microsystems are used to interact with and measure composition and/or concentration of reagents in the ambient. Application areas: - environmental monitoring, e.g., air pollution or water quality control; - security systems, e.g., combustible gas analyzers, explosives detectors; - pharmaceutical industry, i.e., drug discovery, drug delivery (immunoassays); - medical diagnostics, i.e., blood analysis, HIV and hepatitis testing, DNA tests (Alzheimers, heart failure, stroke, sepsis); - food industry, i.e., quality monitoring (pH meters); - medical implants (Cochlea implants, neural probes). Issues: 1) Direct exposure to the environment by definition, there always is a part of chemical microsystem exposed to the environment. It causes signal drift and enhanced noise; 2) Selectivity (any kind of ions can be adsorbed whereas we usually need sensitivity to one species only); 3) Chemical stability and biocompatibility (if chemical reactions occur, sensor corrodes whereas multiple sensing operations over long time would be preferred in most (C) Andrei Sazonov 2005, 2006 cases).
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Example: ISFET (Ion Sensitive Field Effect Transistor). Applications: - pH meters (water quality testing, acidity testing for the food industry milk, cheese, juices, soft drinks, wine, ).
Principle: - the channel area of a FET is exposed to the ambient (solution). The concentration of H+ ions in the solution changes the FET drain current at fixed Vds. The feedback adjusts Vgs to keep the Id constant. Hence Vgs is proportional to [H+] and therefore to pH. Fabrication: - surface micromachining (c-Si or glass).
suspended gate passivation
Vgs
S p-Si substrate
D
Vds
gate SiO2 reference ISFET FET (C) Andrei Sazonov 2005, 2006
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Passive (chemiresistors, chemicapacitors)
Electrochemical (pH-meters)
Chemical sensors
Acoustic wave based (SAW)
Work function based (ISFET, CHEMFET)
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Biosensors
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Chemical sensors. Sensing mechanism:
Environment
Sensor parameter
Signal
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Passive sensors. 1. Chemiresistor. Resistance of the sensitive layer between two electrodes is modified depending on the concentration of the analyzed chemical in the environment. To obtain high sensitivity, the electrodes are interdigitated. Example 1: NH3 and NO2 sensor. Au electrodes (50 interdigitated pairs) 25 m wide, 7.25 mm overlap length, 25 m interelectrode gap. Deposited on top of SiO2 coated c-Si substrate. Coated with 45 layers of polymer (phtalocyanine), each layer 2.5 nm thick. Sensitivity: 0.5-2 ppm. Response time: 1 min. Chemically sensitive layer (polymer) Metal (Au) SiO2
Substrate (C) Andrei Sazonov 2005, 2006
(c-Si, glass)
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Metal electrodes should form ohmic contacts with selective layer. Gold is the best option. Signal: can be DC or AC. In AC mode (about 1 kHz), signal-to-noise ratio can be improved. The signal drift can be eliminated by using passivated reference resistor. Applications: gas sensors (NH3, NO2, Hg vapor). Problems: poor selectivity, non-linearity, long response time.
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Example 2: Metal-oxide gas sensor. Gases adsorbed on the surface of conductive metal oxides (SnO2, ZnO, TiO2) change the resistance. Generally, adsorbed oxygen atoms trap electrons reducing the resistance: O2 + 2e- 2O-. Combustible gases react with oxygen to form H2O and release electrons; resistance decreases: H2 + O- H2O + e-, 2H + O- H2O + e-, CO + O- CO2 + e-. Thus, the change in the resistance depends on the change in the concentration of oxygen (CO) or combustible gases. SnO2 gas sensor detects CO and H2. The concentration range detectable: > 1000 ppm in air. Respective resistance ratio (Rs/R0): < 1 (air level ~ 5). Sensor is non-selective. SnO2 Metal contacts SiO2 Poly-Si heater 2005,membrane (C) Andrei Sazonov Si 2006
104 10
2
G, Ohm-1 105
PCO, kPa
8
103
104
2. Chemicapacitor. Dielectric constant of the sensitive layer varies with analyte concentration. Design may be similar to that for chemiresistor interdigitated electrodes, polymer layer on top, insulating substrate. C, pF The response is non-linear. Applications: humidity sensing, CO, CO2, CH4.
0.05 1 kHz 10 kHz 100 kHz 0.01 1 2 Pp, kPa 0.1 100 Hz
Example: integrated humidity/temperature sensor. c-Si substrate, p-n junction diode as temperature sensor, metal capacitor with spin coated polymer dielectric, which absorbs the moisture. The signal is AC (1kHz range). The response time is 1-2 s.
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3. Work function based sensors. The work functions at the interfaces of metal-insulator-semiconductor structure can be modified. ADFET. FET with very thin gate oxide (< 5 nm) and air gap. Gas molecules adsorb on the oxide surface and modulate drain current. Drawbacks: - no selectivity; - high noise level; - poor stability (SiO2 degrades); - properties drift due to native oxide growth. Air gap and suspended gate design improves noise and selectivity (sensitive layer can be attached to the gate).
optional S G sensitive D layer SiO2 p-Si substrate
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Pd gate MOS. Hydrogen adsorbs well onto Pd surface, decomposes: H2 2H, diffuses through Pd and adsorbs on Pd/SiO2 interface. Pd gate This decreases flat-band voltage and thus reduces VT. D Application: hydrogen sensors.
+ S ----p-Si substrate
VT =
SiO2
N
0
Pd
SiO2
p-Si Ec EF Ev
H
VT threshold voltage shift; dipole moment of interfacial hydrogen ( = qd, d oxide thickness); N surface density of adsorption sites (for Pd, N = 1.67x1019 m-2); fraction of surface sites covered (01).
Example: calculate VT for 25m x 500m MOS with 50nm oxide and 10 ppm H2 concentration. 1.6 *1019 Andrei 8 * 1.67 *1019 * 2 * 105 (C) * 5 * 10 Sazonov 2005, 2006 11 VT = = 0.06V = 60mV Solution: 12
8.85 * 10
Ion sensitive MOS ISFET and CHEMFET. In ISFET, gate dielectric is directly exposed to the environment. Therefore, drain current is modulated by ion concentration on the oxide surface. The gate electrode is located nearby to provide constant Vgs. The gate current is modulated by both Vgs and ions, and by keeping Id constant, we get linear relationship between Vgs and pH. CHEMFET responds to specific ions. CHEMFET = ISFET + ion-specific membrane (organic).
reference FET gate
ISFET
passivation
passivation
organic layer
S p-Si substrate
D
S p-Si substrate SiO2
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D
ISFET
CHEMFET
SiO2
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VT, mV 3 mm +100 S 15 m D 3 mm 0 100 0 5 pH 10
gate
reference FET
ISFET
The output signal may be non-linear; linearization is required. Sensitivity: 50-100 mV/pH Linear range: 1-13 pH Precision: 0.05 pH (2.5-5 mV)
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Electronic Nose concept, design, fabrication and applications.
1. Why do we need E-nose? 2. How to make E-nose? 3. Chemical sensor array a core of E-nose. 4. Fabrication of E-nose. 4. Applications: - food processing; - explosives detection; - alcohol detection; - hazardous chemical detection.
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What is an e-nose?
Electronic nose is a microsystem that recognizes a compound or a combination of compounds in a gaseous environment.
Why do we need e-nose?
1) To avoid unnecessary casualties (environment control in areas with potential chemical hazard); 2) To increase the productivity in chemical industry, food processing, etc.); 3) For security purposes (airport security, subway security, etc.).
E-nose:
1) Sensitive; 2) Versatile.
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Electronic nose: principle of operation
Issue: each chemical sensor is usually either non-selective or selective to one compound only. Solution approach: Use of array of sensors, each of which is coated with different sensitive layer. Each sensitive layer may be sensing several chemicals (say, sensor 1 may be sensitive to CO2, H2O, NH3; sensor 2 to H2O; sensor 3 to CO, CO2; sensor 4 to NH3, H2O; etc.) The pattern recognition program analyzes the response of the array and extracts the information on the nature and the concentration of unknown chemical. analyte analyte
1
sensors: 2 3
n
Chemical 1
Chemical 3 Chemical n
Pattern recognition
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Output signal
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Chemical 2
Components of an e-nose:
1) Chemical sensor array; 2) Micropump microfluidic + channels for sampling control; 3) Computer/PDA with pattern recognition software; 3) Robotic vehicle (optional) for autonomous/remote operation.
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Chemical sensor array:
An array of various chemiresistors (typically polymers filled with metal nanopartilces); Polymer film swells as it absorbs chemical resistance increases; Resistance is proportional to chemical concentration; Each polymer has its individual known response to each of chemicals to be detected; By comparing responses of all resistors (resistance pattern) with reference data (pattern recognition program), the chemical and its concentration are detected.
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E-nose parameters:
Fabrication: surface micromachining (metal electrodes spin coated with polymer films 10nm-1m thick); Sensitivity: depending on the chemical and the environment, could be as low as 0.1ppb. Typically 1 ppm. Response time: Depends on the polymer film thickness and on the sampling algorithm. Varies from < 0.1s to 100s. Response features: Like a mammal nose, e-nose is sensitive to differential signal (changes in the concentration) ambient odor is in the background); In case of mixed odor, individual concentrations can be subtracted by using pattern recognition program.
E-nose response diagram.
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4. Acoustic wave sensors. Acoustic waves propagated through the sensor area are changed by the adsorption of the analyte. Acoustic wave generation: usually piezoelectric. Applications: detection of chemicals. Example: Surface acoustic wave sensor. In SAW sensor, acoustic waves generated by voltage pulses applied to interdigitated electrodes are propagated along the surface and sensed by another set of electrodes. The sensor made of piezoelectric material operates at the resonant frequency. Ambient molecules bound to the surface shift this frequency:
f = kf02m/A,
k constant; f0 resonant frequency; m mass of surface-bound molecules; A - active area.
Drive/sense electrodes
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5. Biosensors. Any sensor that involves biologically derived molecules. Advantage: selectivity. Drawback: irreversibility.
Analyte
Biomolecule layer Sensor (ISFET, SAW,) Electrical output Biosensor
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Immobilization: - membrane entrapment (semipermeable polymer membrane e.g., polyimide membrane with 200nm pores is permeable to viruses or DNA but not to bacteria); - physical adsorption (sensor surface to favor adsorption of specific species e.g., proteins are attached well SiO2 but not to hydrogen plasma treated oxide); - matrix entrapment (porous encapsulation matrix is formed around the biomaterial); - covalent bonding (the surface contains the bonds to which specific biomaterial binds e.g., antibody coated Si).
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Example: ISFET with antibody coating. Principle: On the sensor surface, a layer of biomolecules is immobilized. Biomolecules are usually enzymes proteins well known as metabolism catalysts (oxidants, hydrolytes, etc.). Enzymes bind with specific target compound covalently. Enzymes can be engineered for specific targets (e.g., HIV virus or glucose molecule), thus making highly selective sensor.
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Example: Fluorescent Immunoassays. Principle: Immunoassay is a technology to identify and quantify organic and inorganic compounds. Specifically designed antibodies highly specific to target compound bind with it producing the output signal. Immunoassays are simple and quick to use. ELISA = Enzyme Linked ImmunoSorbent Assay
Detection limit: 1 ppt to 1ppm. absorption
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fluorescence
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Example: DNA microarray (DNA chip). Principle: On top of the substrate (transparent), various single stranded DNA parts labeled with fluorescent dyes are immobilized. Since DNA binds only with complementary pairs, standard DNA microarrays containing a variety of DNA parts are used to identify unknown DNA fragments. Fluorescence occurs only in case of complementary bonding.
Fluorescent microarray micromachined on top of LED.
Printed fluorescent DNA microarray.
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ENFET. This device uses covalent bonding of a molecule to which a specific receptor antibody then adsorbs.
reference electrode
Enzyme coated CHEMFET gate is able to bind antibodies. After that, target is added; the target bound by antibody changes pH proportionally to the amount bonded, which is sensed by CHEMFET.
passivation
enzyme layer
S p-Si substrate
D
SiO2
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Example: glucose level monitoring device. A Pt film has an enzyme called glucose oxydase (an oxydant) immobilized on its surface. Thin porous polymer membrane protects it. Glucose diffusing from solution through membrane is oxydized to gluconic acid, which in turn converts enzyme to its reduced form (oxygen removal).
Enzyme layer
Metal contacts
Blood oxygen then reacts with enzyme, and products inc...