SPR (Surface Plasmon Resonance) Chemical Sensing Microsystems

1

An Introduction to Chemical and Biological
Sensors Denise Wilson, Associate
Professor Department of Electrical
Engineering University of Washington NSF/RISE
Workshop/Short Course Development and Study of
Advanced Sensors and Sensor Materials July 10,
2006
2
Outline

• Classes of Chemical and Biological Sensors
• Single Stage Transduction (Solid State I)
• Multiple Stage Transduction (Solid State II)
• Single Stage Transduction (Optical I)
• Multiple Stage Transduction (Optical II)
• Performance Metrics
• Steady-state, short term
• Steady-state, long term
• Transient

3
Single Stage Transduction (Solid State I)

• Class Definition Biochemical Activity/Energy is
  directly converted to Electrical Energy
• Electrochemical Sensors Ion interaction
  (chemical signal) with a functionalized
  (partially or fully selective) material induces a
  separation of charges (electrical signal)
• Basic Electrochemical Cell
• Potentiometric voltage is measured at zero
  current draw
• Amperometric current is measured at constant
  voltage
• Variations on the Electrochemical Cell
• FET (Field Effect Transistor) Based Devices
• LAPs (Light addressable potentiometric sensors)
• Conductivity Based Sensors (Chemiresistors)
  adsorption or absorption of molecules onto a
  functionalized (partially or fully selective)
  material induces a change in resistance

4
Single Stage Transduction (Solid State I)

• Basic Electrochemical Cell

• Basic Operation
• Ions exchange electrons with the metal electrode
• With the reference electrode in a controlled
  and constant way
• With the working electrode in a manner
  dependent on analyte concentration
• The separation of charges is the electrical
  signal that represents the (bio) chemical signal
  at the electrode(s)

5
Single Stage Transduction (Solid State I)

• Basic Electrochemical Cell Signal Measurement
• Potentiometric In the presence of zero current,
  the voltage induced by the separation of charges
  (between working and reference electrode) is
  measured.
• Governed by the Nernst Equation
• Voltage E1o - E2o (RT/nF) ln (C1/C2)
• E1o standard electrode potential of ion
  interacting with electrode 1
• E2o standard electrode potential of ion
  interacting with electrode 2
• C1 concentration of ion 1 at electrode 1
• C2 concentration of ion 2 at electrode 2
• Demonstrates no scaling penalty (same sensitivity
  for smaller devices)
• Reference electrode materials and surrounding
  solutions are chosen for stability (eg. Ag/AgCl)
• Working electrode materials are designed or
  chosen for analyte selectivity
• Selectivity controlled through electrode design
  or permeable membranes

6
Single Stage Transduction (Solid State I)

• Basic Electrochemical Cell Signal Measurement
• Amperometric In the presence of a controlled
  voltage, the current between working and
  reference electrodes is measured.
• Ions are consumed in the measurement process
  (non-equilibrium)
• Current
• Dependent on conductivity of solution
• Responds only to ions whose redox potential lt
  applied potential
• Possesses inherent scaling (miniaturization)
  penalty that reduces sensitivity and sensor
  performance.
• Reference and working electrode materials chosen
  on same basis as potentiometric operation
• Selectivity controlled through
• Electrode design or permeable membranes or
  applied voltage

Current
Applied Potential
7
Single Stage Transduction (Solid State I)

• Variations on the Basic Electrochemical Cell
  ChemFET
• Potentiometric measurement is inherent in FET
  structure (zero gate current)
• Ions interact with interface between gate and
  insulator layer
• Induced charge is seen as field effect in
  underlying FET channel
• Conductive gate is used to provide an
  electrical reference electrode
• Example
• NMOSFET
• Analyte of interest negative ion
• Increased concentration higher induced negative
  surface charge which must be overcome for FET to
  conduct current higher threshold voltage

Conductive Gate
Negative Ions
FET Insulator

n
n
Drain
Source
p
Positive (induced) charge
8
Single Stage Transduction (Solid State I)

• Variations on the Basic Electrochemical Cell
  ISFET
• Gate/Insulator combination layers that provide
  desired selectivity are limited to a few analytes
  (e.g. palladium/oxide for measuring hydrogen)
• A wider selection of insulator layers with
  desired selectivity is possible.
• Removal of the gate reintroduces need for a
  reference electrode
• Reference electrode in same sensing solution
  introduces instability
• Vulnerability of insulator layer to trapped
  charge introduces drift.
• Example
• N-ISFET with a negative ion of interest (same
  basic operation as ChemFET)

Reference Electrode
Negative Ions
FET Insulator

n
n
Drain
Source
p
Positive (induced) charge
9
Single Stage Transduction (Solid State I)

• Variations on the Basic Electrochemical Cell
  ENFET
• Immobilized enzyme attached to surface of
  insulator in ISFET structure
• Increases sensitivity (through catalytic enzyme
  activity)
• Increases selectivity (through inherent
  functionalization of selected enzyme)
• Insulator is partially protected from trapped
  charge (by enzyme layer)
• ENFET retains many of the disadvantages of the
  ISFET structure

Reference Electrode
Ions of interest
Immobilized Enzyme
FET Insulator

n
n
Drain
Source
p
Induced Charge
10
Single Stage Transduction (Solid State I)

• Variations on the Basic Electrochemical Cell
  LAPs
• Light, rather than the FET, structure is used to
  amplify the induced charge from electrochemical
  interactions at the sensor surface
• Requires an external light source and optics for
  operation
• Eliminates need for drain and source electrodes
• A single gate is required for an entire array
  of sensors
• Active sensing area is determined by illumination
  area.

AC Light Source
11
Single Stage Transduction (Solid State I) pH
ChemFETs
The sensors are designed and fabricated in a
standard CMOS process (1.5 micron AMI). Various
combinations of Silicon Nitride and Aluminum
oxide, native to the CMOS process are used for pH
sensitivity. These designs are extensions of
designs and results initially presented by J.
Bausells, J. Carrabina, A. Errachid, A. Merlos,
Ion-sensitive field-effect transistors
fabricated in a commercial CMOS technology,
Sensors Actuators B Chemical, 7 Sept 1999,
B57(1-3), 56-62.
pH Sensor (8 Total)
12
M2FETThe M2FET uses the second layer of aluminum
in a standard CMOS process for pH sensitivity.
Aluminum oxide grows on top of the aluminum layer
when exposed to an oxygen environment, providing
a pH sensitive layer that is then measured via
the underlying field effect (MOS) structure
Single Stage Transduction (Solid State I) pH
ChemFETs
13
M2FETThe results show sub-microamp differences
between the drain currents of the FET when
operated in the linear (ohmic) region.These
changes in drain current reflect changes in
threshold voltage of the FET induced by
accumulation of charge (OH- ions) on top of the
aluminum oxide layer.
Single Stage Transduction (Solid State I) pH
ChemFETs
14
Single Stage Transduction (Solid State I) pH
ChemFETs
These sensors use the overlying passivation layer
(Silicon Nitride) as the pH sensitive layer (the
bottom structure is an interdigitated version of
the top structure)
15
Single Stage Transduction (Solid State I)

• Conductivity-Based Sensors (Chemiresistors)
• Composite Polymer
• Combination of stable, conductive material (e.g.
  carbon black) and
• Chemically sensitive, insulating material
• Molecule in sensing environment adsorbs into
  polymer sensor
• Carbon black molecules stretch
• Conductivity decreases resistance increases
• Highly sensitive to humidity (caused polymer to
  swell)

http//nsl.caltech.edu/resnose.html
16
Single Stage Transduction (Solid State I)

• Conductivity-Based Sensors (Chemiresistors)
• Metal-Oxide Sensors
• Composed of metal-oxide and a catalyst to enhance
  selectivity
• Oxygen naturally binds to the sensor surface
• Binding processes extract electrons from the bulk
• Analytes of interest in the sensing environment
  bind with Oxygen
• Electrons are re-injected into the bulk
• Conductivity increases (resistance decreases)
• Type of oxygen (and resulting sensitivity) is
  dependent on temperature
• Sensors are highly sensitive to humidity (which
  blocks binding sites)

O2- O2- O2- O2- O2- O2-
O2- O2-
Tin-Oxide with no Analyte Present
Tin-Oxide with Analyte Present
17
Multiple Stage Transduction (Solid State II)

• Class Definition Biochemical Activity/Energy is
  converted to an intermediate form of energy
  before being converted to Electrical Energy
• Example Acoustic Wave Devices
• Basic Operation Input path
• an AC voltage is used to piezoelectrically
  convert
• Electrical energy to
• Mechanical energy (a pressure wave) propagating
  through a material
• Basic Operation Output path
• Loss (attenuation) and
• Delay (phase changes) of mechanical energy (the
  pressure wave) are affected by
• Viscoelastic properties of the material and
• Overall mass of the active sensing area which is
• Responsive to Biochemical binding and events on
  the surface of the sensor
• Altered mechanical energy is converted back to
  Electrical Energy

18
Multiple Stage Transduction (Solid State II)

• Classes of Acoustic Wave Sensors
• Bulk Acoustic Wave basic operation
• Wave moves parallel to the surface of the sensor
  and
• Permeates through the entire material
• Bulk Acoustic Wave characteristics
• Poor Sensitivity only surface wave responds to
  biochemical activity
• Stable on a quartz substrate
• Relatively Inexpensive
• Strong cross-sensitivity to temperature

Direction of Propagation
Electrodes
Direction of Motion
19
Multiple Stage Transduction (Solid State II)

• Classes of Acoustic Wave Sensors
• Surface Acoustic Wave basic operation
• Wave moves perpendicular to the surface of the
  sensor and
• Propagates only on the surface of the material
• Surface Acoustic Wave characteristics
• Frequencies of operation on the order of 100s of
  MHz and GHz
• High Sensitivity surface wave is large part of
  overall activity
• Poorly suited to measurement in liquid (due to
  perpendicular propagation)
• Relatively Expensive (high measurement overhead)

Direction of Motion
Electrodes
Direction of Propagation
20
Multiple Stage Transduction (Solid State II)

• Classes of Acoustic Wave Sensors
• Shear Horizontal Surface Acoustic Wave
• Wave moves parallel to the surface of the sensor
  and
• Propagates only on the surface of the material
• Difficult to fabricate requires careful control
  of cutting piezoelectric material
• Can be used in liquids
• Shear Horizontal Acoustic Plate Mode
• Electrodes on one side of a plate generate a
• Pressure wave that is guided through the bulk of
  the material
• To the other side of the plate where the sensing
  environment is located
• Across the plate and back down to the electrodes
  on the opposite side of the plate
• Wave moves parallel to the surface of the sensor
• Electrodes and electronics are protected from the
  sensing environment
• Moderate sensitivity active area is not
  optimal percentage of overall sensor volume
• Sample Application detect mercury levels in
  drinking water

21
Single Stage Transduction (Optical I)

• Class Definition Optical energy (which is
  directly related to biochemical behavior) is
  directly converted to Electrical Energy
• Luminescence Spectroscopy light emitted by a
  system is a function of biochemical
  activity/energy
• Chemiluminescence emission light represents
  biochemical reactions
• Fluorescence emission light quickly (on the
  order of ns) indicates presence of particular
  molecules
• Electrons are excited into singlet state (paired
  with opposite spin electron) by incoming light
  radiate energy in the form of light upon
  returning to ground state
• Phosphorescence emission light slowly (on the
  order of ms) indicates presence of particular
  molecules
• Electrons are excited into triplet states (paired
  with same spin electron) by incoming light
  radiate energy in the form of light on returning
  to ground state but take longer because the
  triplet state is forbidden.
• Fluorescence/Phosphorescence Spectroscopy
• Input Energy optical
• Output Energy optical converted to electrical
  through a photodetection system

22
Single Stage Transduction (Optical I)

• Fluorescence Analysis Systems
• Regardless of the color of light input, the
  output (emission) spectrum is the same.
• The spectrum (color) of the input light
  influences only efficiency of the emission

23
Single Stage Transduction (Optical I)

• Traditional Fluorescence Analysis Systems

Sample
Signal Processing
Photomultiplier Tube
Optical Dispersion
24
Single Stage Transduction (Optical I)

• Portable Fluorescence Analysis Systems

Sample
Signal Processing
Photodiode Array
Optical Dispersion
25
Single Stage Transduction (Optical I)
Fluorescence Analysis
Optimization Schemes for LED-based (miniaturized)
systems
In this case, input light is transmitted
(inadvertently) to the output path thus
optimization involves reducing the overlap
between excitation (input) light and the emission
spectrum. Optimization criteria depend on system
configuration and experimental constraints.
(a) Best Configuration
(b) Worst Configuration
26
Multiple Stage Transduction (Optical II)

• Class Definition Biochemical Activity/Energy is
  converted to Optical Energy before being
  converted to Electrical Energy
• Surface Plasmon Resonance
• Biochemical events/analytes of interest influence
  refractive index of the sensing environment very
  close (within 100nm) of the SPR surface (in the
  evanescent field).
• Refractive index influences how input light is
  reflected back to the output path (as a function
  of incidence angle or wavelength, depending on
  the system configuration.
• Transduction Path
• Light Energy is converted to
• Surface Charge Oscillations (surface plasmons)
• The unconverted Light Energy is then converted to
• Electrical Energy (via Photodetection) in the
  output path

27
Multiple Stage Transduction (Optical II) SPR
When the wave vector from a white light source
closely matches that of the surface plasma wave
at the metal-sample interface on the probe,
reflected light is significantly attenuated
(compared to the attenuation in the reference
media where no analyte is present)
28
Multiple Stage Transduction (Optical II) SPR

• The Big Picture
• Why SPR?
• Highly sensitive (10-4 to 10-6 RI units)
• Very local (10-100nm from sensing surface)
• Directly indicative (of interactions between
  sensor and environment)
• Relatively unencumbered by sampling overhead
  (e.g. tagging, mixing, etc)
• Readily referenced to compensate for background
  fluctuations (e.g. drift)
• How is it used (SPR transduction mechanism)?
• Non-functionalized bulk refractive index
• Functionalized specific analytes
• The Full Spectrum of SPR-based instruments
• User-Intensive, Single Measurements Biacore
• User-Intensive, Single Field Measurements TI
  Spreeta (Chinowsky/Yee)
• Distributed and Autonomous, Multiple
  Measurements
• Insertion-based probes
• Compact signal processing
• Streamlined, robust optical path

29
Multiple Stage Transduction (Optical II) SPR

• Point of resonance can be detected at a
• Particular angle (constant wavelength
  interrogation)
• Particular wavelength (constant angle
  interrogation)
• Constant Angle
• Polychromatic light source at constant angle of
  incidence
• Constant Wavelength
• Monochromatic light source at different angles of
  incidence

Constant Angle is chosen here for inexpensive
light source, easy alignment, and simpler, more
compact configuration ( less overhead)
30
Multiple Stage Transduction (Optical II) SPR

• Sampling Options
• In-line
• Dip insertion-based probe

• The probe configuration is
• easily replaced, easy to use
• Less prone to sensor layer blocking,
• but can be
• more sensitive to ambient fluctuations
• more susceptible to fouling

31
Multiple Stage Transduction (Optical II) SPR
Increasing RI
Raw Data (background overwhelms resonance)
Referenced Data (Resonance is evident)
32
Multiple Stage Transduction (Optical II) SPR
Approach 1 (Traditional)
Software
High Resolution Photodetection
Approach 2 (Voltage-Mode, Partially Integrated)
Software
Integration Time Programming
Low Resolution Photodetection
Flatlining Reference Ratio
33
Multiple Stage Transduction (Optical II) SPR
34
Multiple Stage Transduction (Optical II) SPR
Approach 2
All Designs are mixed signal, fabricated in
standard CMOS
Approach 4
Approach 3
35
Multiple Stage Transduction (Optical II) SPR
15 pixel array fabricated on a 1cm2 die in the
1.5 micron AMI process through MOSIS
2mm
36
Multiple Stage Transduction (Optical II) SPR
Approach SOC Integration Size (l X l )
Traditional None Big
Voltage Mode Partial 200 X 1800
Pulse Mode Full 200 X 1200
Current Mode Full 200 X 1000
Approach Traditional Voltage Mode Pulse Mode Current Mode
Prediction Error 6.07 6.05 7.8
RI Resolution 5 X 10-4 2 X 10-4 6 X 10-4
37
Performance MetricsChemical and Biological
Sensors

• Steady State, Short Term
• Sensitivity Change in output/Change in Input
• Chemiresistor DR/DC
• SPR Dl/DRI
• Resolution
• Input smallest detectable change in input
  parameter
• Output smallest detectable change in output
  parameter
• Offset output in the presence of no input
• Detection limit minimum detectable change
• Dynamic range maximum - minimum detectable
  (input) signal
• Signal to Noise Ratio ratio of useful
  information to non-useful information at any
  given signal level
• Selectivity practical ratio of sensor response
  to (a) analyte of interest divided by response to
  (b) most significant interferent.

38
Performance MetricsChemical and Biological
Sensors

• Steady State, Long Term
• Stability Change in output for a constant input
  over a period of time several orders of magnitude
  greater than the response time of the sensor.
• Drift Loose term often used in place of
  stability -- means the non-monotonic change in
  sensor output over time in response to the same
  input conditions.
• Transient
• Hysteresis maximum difference in output
  obtained when sensor input is increased as
  compared to sensor input decreased.
• Response time
• Propagation delay how long before a change in
  the sensing environment is reflected in a change
  in the sensor output (delay between a 50 change
  in the input and a 50 change in the output of
  the sensor is typically chosen)
• Rise/Fall time time required for the sensor
  output to rise (or fall) from 10 of its final
  output to 90 of its final output.