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Andreas Hierlemann* and Henry Baltes

Physical Electronics Laboratory, ETH Zurich, Hnggerberg, HPT H 4.2, CH-8093 Zurich,
Switzerland. E-mail: hierlema@iqe.phys.ethz.ch; Fax: +41 1 633 1054; Tel: +41 1 633 3494

TUTORIAL REVIEW

THE

CMOS-based chemical microsensors

ANALYST

I-SECTION

www.rsc.org/analyst

Received 2nd September 2002, Accepted 14th November 2002


First published as an Advance Article on the web 4th December 2002
1
2
3
3.1
3.2
4
4.1
4.1.1
4.1.2
4.2
4.2.1
4.2.2
4.3
4.3.1
4.4
4.4.1
4.4.2
4.4.3
4.4.3.1
4.4.3.2
4.5
4.5.1
4.5.2
5
6
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Introduction
CMOS technology
Micromachining techniques
Bulk micromachining
Surface micromaching
CMOS-based chemical sensors
Chemomechanical or mass-sensitive sensors
Flexural-plate-wave or Lamb-wave devices
Resonating cantilevers
Thermal sensors
Catalytic thermal sensors (pellistors)
Thermoelectric or Seebeck-effect-based sensors
Optical sensors
Bioluminescent bioreporter integrated circuits
(BBIC)
Electrochemical sensors
Voltammetric/amperometric sensors
Potentiometric sensors (chemotransistors)
Conductometric sensors
Chemoresistors
Chemocapacitors
Monolithic integration of different transducers
CMOS multiparameter biochemical sensor
CMOS single-chip gas microsensor system
Outlook
Acknowledgements
References

1 Introduction
The rapid development of integrated circuit (IC) technology
during the past decades has initiated many initiatives to
fabricate chemical sensors on silicon or CMOS substrates

Andreas Hierlemann received a Diploma in Chemistry


in 1992 and a PhD in Physical Chemistry in 1996
from the University of Tbingen, Germany. After
working as a Postdoc at Texas A&M University,
College Station, TX (1997), and Sandia National
Laboratories,
Albuquerque,
NM (1998), he moved to
ETH Zurich in Switzerland
where he is currently a
member
of
the
technical
staff. The focus of his research activities is on CMOS
transducers, chemical sensors
and interfacial design.

(CMOS: Complementary Metal Oxide Semiconductor).1,2 The


largely two-dimensional integrated circuit and chemical sensor
structures processed by combining lithographic, thin film,
etching, diffusive and oxidative steps have been recently
extended into the third dimension using micromachining or
MEMS (MEMS: MicroElectro-Mechanical Systems) technologiesa combination of special etchants, etch stops and
sacrificial layers.39 A variety of micromechanical structures
including cantilever beams, suspended membranes, freestanding bridges, etc. have been produced.39 The realization of
microelectronics and micromechanics (MEMS-structures) on a
single chip allows for on-chip control and monitoring of the
mechanical functions as well as for data preprocessing such as
signal amplification, signal conditioning, or data reduction.312
CMOS- or CMOS-MEMS-technology, therefore, provides
excellent means to meet some of the key criteria of chemical
sensors such as miniaturization of the devices, low power
consumption, rapid sensor response characteristics, or batch
fabrication at industrial standards and low costs. Additional
advantages come from the possibility of monolithic cointegration of circuitry and transducers. These include improved
sensor signal-to-noise characteristics due to on-chip signal
processing and analog/digital conversion, or the realization of
smart features on the sensor chip. Drawbacks of using CMOS
technology encompass a limited selection of materials (see
CMOS technology section) and a predefined fabrication process
for the CMOS part. Sensor-specific or transducer-specific
materials and fabrication steps have to be introduced as postprocessing after the CMOS fabrication.13
After a short introduction to CMOS and basic micromachining technologies, we will give an overview on different
types of chemical sensors fabricated in CMOS and CMOSMEMS technology.

Henry Baltes received a DSc degree from ETH Zurich in 1971.


He has held faculty positions at Freie Universitt Berlin and
University of Dsseldorf, Germany, University of Waterloo,
Canada and EPF Lausanne, Switzerland. He worked for Landis
& Gyr Zug, Switzerland (19741982), directing the SolidState Device Laboratory; he held
the Henry Marshall Tory Chair at
the University of Alberta, Edmonton, Canada (19831988), where
he directed a research program in
microsensors; he was a Director of
LSI Logic Corporation of Canada
(19861988), and since 1988 he
has been Professor of Physical
Electronics at ETH Zurich and
Director of the Physical Electronics Laboratory active in silicon
integrated micro-systems.

DOI: 10.1039/b208563c

Analyst, 2003, 128, 1528


This journal is The Royal Society of Chemistry 2003

15

2 CMOS technology
CMOS is the dominant semiconductor technology for microprocessors, memories and application-specific integrated circuits (ASICs).1416 CMOS-chips generally consist of a layered
structure of aluminum, polysilicon, silicon (doped and undoped), silicon oxide and -nitride layers (Fig. 1), which are
fabricated in a defined sequence of material deposition, doping,
lithography and etching steps.1416
Semiconductors conduct electricity but not enthusiastically.
Semiconductor areas that are doped become conductors of
either extra electrons with a negative charge (phosphorusdoping) or of positive charge carriers (boron-doping). The
denomination complementary metal oxide semiconductor is
due to the fact that both, n-type and p-type transistors are
realized on the same substrate, for example on a lightly p-doped
wafer material, that exhibits n-doped areas (n-wells) (Fig. 1).
Both, n-type (NMOS) and p-type (PMOS) transistors are used
to realize logic functions. A CMOS-chip cross-section is shown
in Fig. 1. The p-substrate exhibits n-well areas created by
implantation. Heavily p-doped structures (p+) in the n-well, and
n-doped structures (n+) in the p-substrate form transistor source
and drain. The transistor gate is made of polysilicon on top of
the gate oxide (SiO2). By applying a voltage to the gate via the
polysilicon, electrons or holes are accumulating in the surface
area (field effect) below the gate and thus create a conducting nor p-channel between source and drain. Variation of the gate
voltage thus modulates the source drain current: continuously
within a certain range in analog circuits, on/off in digital
circuits. Several metal layers (Fig. 1: metal 1 and metal 2,
aluminum) are used to wire the transistors. Dielectric layer such
as field oxide, contact oxide, and intermetal oxide (SiO2) serve
as electrical insulation between conducting areas. The silicon
nitride on top serves as passivation and provides electrical and
mechanical/chemical protection of the circuitry. Silicon nitride
and to a lesser extent silicon oxide (or silicon with a native oxide
layer) are durable in case of liquid exposure and are biocompatible, which allows for using CMOS chips also with cells or
living material. CMOS aluminum is neither stable in liquids (or
in air at higher temperatures) nor is it biocompatible, and,
consequently, has to be covered with precious metal coatings
such as gold or platinum. For more details on semiconductor
technology, see, e.g., the standard textbooks of Sze.15,16

acid/hydrofluoric acid lead to isotropic etching (same etch rate


in all directions), others like potassium hydroxide lead to
anisotropic etching, i.e., preferentially etch away the silicon
along certain crystal planes while preserving it in other
directions (Fig. 2a). Typical structures obtained by, e.g.,
anisotropic wet etching through the complete bulk silicon of a
CMOS wafer include membranes consisting of the remaining
dielectric CMOS layers. The thermal oxide serves as an etchstop layer. The resulting membrane structures can be used for
sensors requiring excellent thermal insulation, such as calorimetric chemical sensors or metal oxide-covered microhotplates.
Another technique is dry etching. Again, there is isotropic
etching performed by using, e.g., xenon difluoride or anisotropic etching by reactive-ion-etching (RIE). RIE can be used to
release cantilevers or create bridge structures from preformed
membranes.18
3.2 Surface micromachining
Surface micromachining comprises a number of techniques to
produce microstructures from thin films previously deposited
onto a substrate and is based on a sacrificial layer method (Fig.
2b). In contrast to bulk micromachining, surface micromachining leaves the substrate intact. A sacrificial layer is
deposited and patterned on a substrate. After that, a structural
thin film, in most cases polysilicon, is deposited and patterned,
which will perform the mechanical or electrical functions in the
final device. A selective etchant then removes exclusively the
sacrificial layer material. The thickness of the sacrificial layer
determines the distance of the structural parts from the substrate
surface. Common sacrificial layer materials include silicon
oxide etched by hydrogen fluoride and aluminum etched by a
mixture of phosphoric, nitric and acetic acid.
Clamped beams, microbridges, or microchannels can be
fabricated this way, microrotors and even microgears can be
realized by repeated layer deposition and etching.37,17

4 CMOS-based chemical sensors

One approach to enhance the functionality of IC-based


substrates includes micromachining the bulk substrate, which in
most cases consists of silicon. Silicon can be dry or wet etched
by various techniques.37,17 Some wet etchants such as nitric

Chemical sensors usually consist of a sensitive layer or coating


and a transducer.1925 Upon interaction with a chemical species
(absorption, chemical reaction, charge transfer etc.), the
physicochemical properties of the coating, such as its mass,
volume, optical properties or resistance etc. reversibly change.
These changes in the sensitive layer are detected by the
respective transducer and translated into an electrical signal
such as frequency, current, or voltage, which is then read out
and subject to further data treatment and processing.
A variety of transducers based on different physical principles have been devised. We will follow a classification scheme

Fig. 1 Cross-section of a CMOS-chip. The different layers and materials


include metals (aluminum), silicon oxides, silicon nitride, and polysilicon
on a p-doped silicon wafer with n-well implanted areas.

Fig. 2 Micromachining techniques: (a) bulk micromachining, anisotropic


and isotropic etching, (b) surface micromachining with sacrificial layer,
structural layer and a subsequent etch step.

3 Micromachining techniques
3.1 Bulk micromachining

16

Analyst, 2003, 128, 1528

suggested by Janata20,21 to give an overview on CMOS-based


chemical sensors in the next sections of this review. This
scheme includes four principal categories distinguished with
regard to the transduction principle:20
1. Chemomechanical or mass-sensitive sensors (e.g., mass
changes due to absorption)
2. Thermal sensors (e.g., temperature changes through chemical
interaction)
3. Optical sensors (e.g., light intensity change by absorption)
4. Electrochemical sensors (e.g., potential or resistance changes
through charge transfer)
We will briefly introduce each of those four sensor categories
and then give examples of CMOS-based transducers and
devices. Typical chemically sensitive materials and sensor
applications will be mentioned in the context of the corresponding transducer structures.
4.1 Chemomechanical or mass-sensitive sensors
Chemomechanical or mass-sensitive sensors are in the simplest
case gravimetric sensors responding to the mass of species
accumulated in a sensing layer.2628 Some of the sensor devices
additionally respond to changes in a variety of other mechanical
properties of solid or fluid media in contact with their surface
such as changes of polymer elastic moduli, liquid density and
viscosity,2628 which will not be further discussed here.
Chemomechanical sensor, therefore, is a more appropriate
denomination. Any species that can be immobilized on the
sensor can, in principle, be sensed. As with most of the chemical
sensors, the measurements are taken at a thermodynamic
equilibrium state.
Mass changes can be monitored by either deflecting a
micromechanical structure due to stress changes or massloading (static measurements) or by assessing the frequency
changes of a resonating structure or a traveling acoustic wave
upon mass loading. Both deflection and resonance frequency
change in proportion to stress changes or mass loading on the
device.2628
The most common devices are the thickness shear mode
resonator (TSMR) or quartz microbalance (QMB), and the
Rayleigh surface acoustic wave (SAW) device, both based on
piezoelectric quartz substrates. Both will not be detailed here,
since they are not fabricated in CMOS technology. For more
details on those devices, see refs. 2628.
In the following, we will describe in more detail two CMOStechnology-based micromechanical structures for mass-sensitive devices, (1) flexural-plate-wave devices (FPWs), and (2)
micromachined cantilevers.
4.1.1 Flexural-plate-wave or Lamb-wave devices. The
chief advantage of flexural plate wave devices (FPW) is their
high sensitivity to added mass at a low operating frequency
(typically 310 MHz).29 FPW devices feature plates that are
only a fraction of an acoustic wavelength thick (typically 23
mm). The plates are composite structures (Fig. 3) consisting of
a silicon nitride layer, an aluminum ground plane, and a
sputtered zinc oxide piezoelectric layer, all of which are
supported by a silicon substrate.2632
The interdigital transducers (IDTs) on these devices generate
flexural waves (Lamb waves, Fig. 3) with retrograde elliptical
particle motions as in the SAW devices. The Lamb waves give
rise to a series of plate modes, one of which has a frequency that
is much lower than those of the other possible modes. The
velocity of this unique wave decreases with decreasing plate
thickness. The entire thickness of the plate is set in motion like
the ripples in a flag.2632 The confinement of acoustic energy in
the thin membrane results in a very high mass sensitivity. Since
the Lamb wave causes an elliptical particle movement at the
transducer surface (Fig. 3), the sensitive films are deformed.

The sensitive layer can be deposited on either side of the


membrane. Deposition on the backside (non-processed side of
the wafer) has the advantage, that on-chip-circuitry will not be
exposed to chemicals.2932
Fabrication sequences for monolithic integration of the Lamb
device with CMOS electronics are detailed in refs. 32 and 33.
A variant includes a magnetical FPW actuation scheme based
on Lorentz forces: A metal meander-line is patterned on the
membrane surface, alternating current (AC) is flowing in the
meander transducer and interacts with a static in-plane magnetic
field to generate time-varying Lorentz forces, which in turn
deform the membrane. Magnetic actuation requires an externally applied magnetic field, but eliminates the need for a
piezoelectric layer.34,35 Such layers frequently contain elements
(Zn etc.) that pose contamination problems in IC fabrication.34
Typical FPW applications include the detection of different
organic volatiles in the gas phase by using polymeric layers,31,35,36 or the use of an FPW-based immunoassay for the
detection of breast cancer antigens.37
4.1.2 Resonating cantilevers. A mass-sensitive cantilever
usually is a layered structure composed of, e.g., silicon, silicon
oxide/nitride, and, eventually, metallizations. The cantilever
base is firmly attached to a silicon support (chip). The freestanding cantilever end is coated with a sensitive layer.
There are two fundamentally different operation methods: (a)
static mode: measurement of the cantilever deflection upon
stress changes or mass loading by means of, e.g., a laser via
laser light reflection on the cantilever;3841 (b) dynamic mode:
excitation of the cantilever in its fundamental resonance mode
and measurement of the frequency change upon mass loading4246 in analogy to other mass-sensitive transducers. Method
(a) requires long and soft cantilevers to achieve large deflections, whereas method (b) requires short and stiff cantilevers to
achieve high operation frequencies. Resonators are characterized by their quality factor (Q-factor), which is defined as the
ratio of the resonance frequency and resonator bandwidth: the
higher the Q-factor, the better the frequency stability of the
resonator. The dynamic mode (b) is preferable with regard to
simplicity of the measurement configuration since there is no
need for an optical setup to determine small cantilever
deflection by means of, e.g., laser light reflection.4246 Method
(a) can also be used in liquid media.39,41 The excitation of the
resonant cantilever is performed by applying piezoelectric
materials (ZnO)47 or by relying on Lorentz forces in a magnetic
actuation scheme, which is analogous to that already described
in the context of the FPWs: one or several conductor loops are
patterned along the cantilever edges, AC is flowing in the loops
and interacts with a static in-plane magnetic field to generate

Fig. 3 Schematic of a flexural plate wave device. The side view shows the
different layers and the membrane movement. Interdigitated electrodes are
used for actuation.

Analyst, 2003, 128, 1528

17

time-varying Lorentz forces, which deflect the cantilever.48,49


Another actuation variant includes making use of the different
temperature coefficients or mechanical stress coefficients of the
cantilever layer materials (bimorph effect).4346 The different
materials give rise to a cantilever deflection upon heating or
applying mechanical forces. Cantilever deflection or resonance
frequency changes can be detected by embedding piezoresistors
in the cantilever base.4146 The absolute mass resolution of the
cantilevers is in the range of a few picograms.3846 This high
mass-sensitivity does not necessarily imply an exceptionally
high gas sensor sensitivity since the area coated with the
sensitive layer (on the order of 100 3 150 mm), and hence the
overall sorption matrix volume is very small.43
Fig. 4 shows a CMOS-based cantilever, which is monolithically integrated with feedback electronics.43 The 150 mmlong cantilever consists of mainly silicon as well as vapordeposited and thermal oxide. The bimorph effect is used to
initiate a cantilever vibration by periodically applying electric
pulses to heating resistors embedded at the cantilever base. The
cantilever resonates at its fundamental mechanical frequency of
380 kHz with a quality factor of approximately 1000 in air,
which is comparable to other acoustic-wave-based devices such
as QMB or Rayleigh SAW-device. The Q-factor of the
cantilever sandwich is dependent on the cantilever materials
with silicon offering very favorable properties in comparison to
silicon oxide, nitride or the polymer coating.43 The cantilever
vibration is detected by embedded piezoresistors in a Wheatstone-bridge configuration. The cantilever acts as the frequency-determining element in a feedback oscillation circuit,
which for the first time was entirely integrated on the chip with
a counter. The advantages of the monolithic integration here
include a better frequency stability of the resonator and lower
crosstalk (thermal and electrical) of the different components
leading to a better signal-to-noise ratio of the overall system.
For more details on the electronics, see refs. 4346 and 50.
Typical cantilever applications include the detection of
organic volatiles or humidity in the gas phase by using
polymeric layers,4146,4955 and biosensing in liquid phase such
as the detection of cells,56 or complementary strands of
oligonucleotides (DNA fragments).39
4.2 Thermal sensors
Calorimetric or thermal sensors rely on determining the
presence or concentration of a chemical by measurement of an
enthalpy change produced by the chemical to be detected.19,20,57
Any chemical reaction or even absorption/desorption process
releases or absorbs from its surroundings a certain quantity of
heat. Reactions liberating heat are termed exothermic, reactions
abstracting heat are termed endothermic. This thermal effect
shows a transient behavior: continuous liberation/abstraction of
heat occurs only as long as the reaction proceeds. However,
there will be no heat production and hence no measurable signal

Fig. 4 Micrograph of a 150 mm-long CMOS-integrated cantilever with onchip feedback circuitry.

18

Analyst, 2003, 128, 1528

at thermodynamic equilibrium (DG = 0) in contrast to masssensitive, optical, or electrochemical sensors (see Fig. 15
later).
Conflicting constraints are imposed on the design of a
thermal sensor. The sensor has to interact with the chemical
species (exchange of matter) and thus constitute a thermodynamically open system, but at the same time the sensing area
should be thermally as isolated as possible to achieve maximum
sensitivity.
The liberation or abstraction of heat can be conveniently
measured as a change in temperature, which then is transduced
into an electrical signal. The various types of calorimetric
sensors differ in the way that the evolved heat is transduced.19,20,57
The catalytic sensor (often denoted pellistor58) employs
platinum resistance thermometry, while the thermoelectric
sensor is based on the Seebeck effect.57 Both sensor types
benefit from CMOS integration and will be detailed in the
following sections.
4.2.1 Catalytic thermal sensors (pellistors). The development of the catalytic sensor is derived from the need for a handheld detector for methane to replace the flame safety lamp in
coalmines. The catalytic device measures the heat evolved
during the controlled combustion of flammable gaseous
compounds in ambient air on the surface of a hot catalyst by
means of a resistance thermometer in proximity with the
catalyst. This method is, therefore, calorimetric. The heated
catalyst here permits oxidation of the gas at reduced temperatures and at concentrations below the lower explosive limit
(LEL). The term pellistor originally refers to a device
consisting of a small platinum coil embedded in a ceramic bead,
which is impregnated with a noble metal catalyst .58
Fig. 5 shows a surface-micromachined, free-standing, Ptcoated polysilicon micro-filament (10 mm wide, 2 mm thick)
separated from the substrate by a 2 mm air gap.59,60 Other
designs include micromachined membranes.6166 Heat losses to
the silicon frame are minimized in both designs. By passing an
electric current through the meander, the microfilament is
heated to a temperature sufficient for the Pt-surface to
catalytically oxidize the combustible mixture; the heat of
oxidation is then measured as a resistance variation in the Pt.
The combustion of, e.g., methane generates 800 kJ mol21 heat,
which translates into a corresponding temperature change.
Detailed processing sequences for microbridges are given in
refs. 67 and 68.
Typical applications include monitoring and detection of
flammable gas hazards such as methane,64,68 hydrogen,5961,64
propane,61 or carbon monoxide61,65 in industrial, commercial
and domestic environments at concentrations below the lower
explosive limit (LEL). The LEL is the concentration of gas in air
below which it cannot be ignited.

Fig. 5 Micrograph (SEM) of two meandered polysilicon filaments. The


lower filament is coated with a thin (approx. 0.1 mm) layer of platinum
(CVD). In a differential gas sensing mode, the upper, uncoated, filament
acts to compensate changes in the ambient temperature, thermal conductivity and flow rate. Reprinted from ref. 59 with permission.

4.2.2 Thermoelectric or Seebeck-effect-based sensors.


This type of sensor relies on the thermoelectric or Seebeckeffect.57,69 When two different semiconductors or metals are
connected at a hot junction and a temperature difference is
maintained between this hot junction and a colder point, then an
open-circuit voltage is developed between the different leads at
the cold point. This thermovoltage is proportional to the
difference of the Fermi levels of the two materials at the two
temperatures and thus proportional to the temperature difference itself.57,69 This effect can be used to develop a thermal
sensor by placing the hot junction on a thermally isolated
structure like a membrane, bridge etc. and the cold junction on
the bulk chip with the thermally highly conducting silicon
underneath.46,6972 To achieve a higher thermoelectric voltage,
several thermocouples are connected in series to form a
thermopile. The membrane structure supporting the hot junctions is covered with a sensitive or chemically active layer
liberating or abstracting heat upon interaction with an analyte.
The resulting temperature gradient between hot and cold
junctions then generates a thermovoltage, which can be
measured.
Fig. 6 displays the schematic of a CMOS-based thermopile
consisting of a dielectric membrane with polysilicon/aluminum
thermocouples (Seebeck coefficient: 111 mV K21).46,72,73
CMOS-based thermoelectric sensors are advantageously set up
in a sensor/reference configuration. The system includes two
membranes, one of which is coated with the gas-sensitive
polymer, the uncoated one serves as a reference to compensate
for gas-induced temperature fluctuations.73 The sensing and
reference thermopiles are connected in parallel to the input
stage of a low-noise chopper-stabilized instrumentation amplifier on-chip to record the temperature differences between the
two membranes. The thermovoltage can be translated into a
digital signal on chip using a SigmaDelta analog/digital
converter.74
Processing sequences for the integration of thermoelectric
sensors with circuitry in a CMOS standard process are detailed
in refs. 72 and 75.
Typical applications include the detection of different kinds
of organic volatiles in the gas phase by using polymeric
layers,46,7277 and the biosensing of glucose, urea and penicillin
in the liquid phase by using suitable enzymes.71,7880
4.3 Optical sensors
In comparison to other chemical sensing methods, optical
techniques offer a great deal of selectivity already inherent in
the various transduction mechanisms. Characteristic properties
of the electromagnetic waves such as amplitude, frequency,
phase, and/or state of polarization can be used to advantage.8183 Geometric effects (scattering) can provide additional information. The wavelength of the radiation, e.g., can be
tuned to specifically match the energy of a desired analyte-

Fig. 6 Schematic of a thermoelectric sensor. Polysilicon/aluminum


thermopiles are used (hot junctions on the membrane, cold junctions on the
bulk chip) to record temperature variations caused by analyte sorption in the
polymer.

specific resonance or absorption process. In addition, optical


sensors like any other chemical sensor can capitalize on all the
selectivity effects originating from the use of a sensitive
layer.8183
If a sample is irradiated with visible light or electromagnetic
waves, the radiation can be absorbed (intensity decrease),
scattered (direction randomization, possibly frequency
changes), refracted or reflected (metallic reflection, internal
reflection mediated by evanescent waves) at the interface(s), or
can produce phosphorescence/fluorescence (absorptionemission process) and chemiluminescence (conversion of chemical
energy into light) effects.8183
The generation of light in CMOS or silicon devices is very
difficult since there is no first order transition from the valence
band to the conduction band without the involvement of a
phonon (lattice vibrations).15 However, direct-bandgap semiconductors (IIIV-semiconductors) like gallium arsenide
(GaAs) or indium phosphide (InP) show first-order radiative
electron-hole-recombinations with high quantum efficiency.15
The detection of light is possible with either silicon-based
devices (photodiodes) or other semiconducting materials
(GaAs, InP). Consequently, integrated optical sensors and
systems nowadays mostly are made of IIIV-semiconductors,
which will not be detailed here, but offer the opportunity for
fabrication and integration of lasers, waveguides, phase modulators and detectors on the same chip.84 There is also a wealth
of fiber-optical techniques and integrated optical devices, which
are realized on silicon substrates without making use of CMOS
technology. For details, see review articles.8183, 8588
In this article we will exclusively focus on CMOS-based
optical sensors, an example of which includes an integrated
device making use of bioluminescence.
4.3.1 Bioluminescent bioreporter integrated circuits
(BBIC). This technique employs bioluminescent bacteria
placed on an application-specific optical integrated circuit
(standard CMOS).8991 The bacteria have been engineered to
luminesce, when a target compound such as toluene is
metabolized. Chemical reaction between target compound and
bacteria leads to an excited state of a participating molecule,
which then emits light during transition to the ground state.
Chemical energy is thus directly converted into light energy in
most cases without additional heat generation (cold luminescence). Such processes take place, e.g., in glowworms.
The integrated circuit detects, processes, and reports the
magnitude of the optical signal.8991 The microluminometer
uses the p-diffusion (source and drain diffusions of p-channel
MOSFETs, PMOS, Fig. 1) in the n-well as the photodiode. The
shallow p-diffusion has a strong response to the 490 nm
bioluminescent signal. The entire sensor including all signal
processing and communication functions can be realized on a
single chip. The integrated circuit contains the devices and
circuits to detect the optical signal, to distinguish the signal
from noise, to perform analog or digital signal processing, to
communicate the results, and to perform auxiliary functions
such as temperature assessment or position measurement (Fig.
7).8991
Many types of bioluminescent transcriptional gene fusions
have been used to develop light-emitting bioreporter bacterial
strains to sense the presence, bioavailability, and biodegradation of different kinds of pollutants. The cells here were
entrapped on the chip by encapsulation in natural or synthetic
polymers providing a nutrient-rich hydrated environment.8991
Applications include chemical analysis in gas or liquid phase.
Depending on the integration time of the device, trace amounts
of toluene and naphthalene were detected in the gas phase using
engineered cell colonies of Pseudomonas putida.8991
Similar CMOS-based photodiode or phototransistor structures such as CMOS charge-coupled detector (CCD) imagers
have been used to develop microspectrometers for biochemical
Analyst, 2003, 128, 1528

19

analysis92,93 or smart optical sensor systems to measure light


intensity and color.94,95 FabryPerot-based single-chip microspectrometers (16 addressable FabryPerot etalons) that can be
used, e.g., for chemical analysis are detailed in refs. 95 and
96.
4.4 Electrochemical sensors
Electrochemical sensors constitute the largest and oldest group
of chemical sensors. Many of them are commercially available.
Electrochemical sensors make use of electrochemical or chargetransfer reactions, i.e., charge transfer from an electrode to a
solid or liquid sample phase or vice versa. Chemical changes
take place at the electrodes or in the probed sample volume, and
the resulting charge or current is measured. Electrode reactions
and charge transport in the sample are both subject to changes
by chemical processes (analyte exposure) and hence at the base
of electrochemical sensing mechanisms.1925,97
An electrochemical sensor is always composed of at least two
electrodes with two electrical connections: one through the
probed sample, the other via transducer and measuring
equipment. The charge transport in the sample can be ionic,
electronic or mixed, while that in the transducer branch is
always electronic.
Electrochemical sensors are usually classified according to
their electro-analytical principles.20,21,24 Voltammetric sensors
are based on the measurement of the currentvoltage relationship. A potential is applied to the sensor, and a current
proportional to the concentration of the electro-active species of
interest is measured (amperometry is a special case of
voltammetry, where the potential is kept constant). Potentiometric sensors are based on the measurement of the potential at
an electrode at equilibrium state, i.e., no current is allowed to
flow during the measurement. The measured potential is
proportional to the logarithm of the concentration of the electroactive species (Nernst-equation). Conductometric sensors are
based on the measurement of a conductance by applying an AC
potential with small amplitude to a pair of electrodes in order to
prevent polarization. The presence of charge carriers determines
the sample conductance.
Another method of classification is according to electronic
components.6,25 There are chemoresistors, chemocapacitors
and chemotransistors. We will use the electroanalytical principles as the superordinated scheme and use the component
notation within the different sections. We will restrict to
CMOS-based systems and omit a wealth of literature on other
electrochemical sensor designs, for details of which we refer to
literature.1925,9799
4.4.1 Voltammetric/amperometric sensors. Two different
electrode configurations are normally used for voltammetric/

Fig. 7 Micrograph of a bioluminescent bioreporter integrated circuit


(BBIC). The circuitry blocks are in the upper part, the photodetectors in the
lower part of the chip. Reprinted from ref. 90 with permission.

20

Analyst, 2003, 128, 1528

amperometric measurements. The two-electrode configuration.21,97 consists of a reference electrode (RE) and a working
electrode (WE). The disadvantage of this method is, that the RE
carries current and may become polarized if it is less than
hundred times the size of the WE. Material consumption due to
the current in the RE is another problem. A better approach is
hence the use of a three-electrode-system21,97 in a potentiostatic
configuration. An additional auxiliary electrode (AE, sometimes denoted counter electrode CE) is introduced for current
injection in the analyte.97 The reference electrode is now a true
RE with a well-defined potential since no current is flowing
through the RE. The potentiostat controls the current at the
auxiliary electrode as a function of the applied potential. This is
realized in practice with an operational amplifier.97
The measured current at any given potential difference
depends on the material properties, the composition and
geometry of the electrodes, the concentration of the electroactive species (presumably the target analyte) and the mass
transport mechanisms in the analyte phase.20,24,97 Among those
are migration, the movement of charged particles in an electric
field, convection, the movement of material by forced means
like stirring or from density or temperature gradients, and
diffusion, the movement of material from high-concentration
regions to low-concentration regions. The electrochemical
reactions at the electrodes are normally fast in comparison to the
transport and supply mechanisms. Since convection in the
electrode vicinity is avoided, and migration is suppressed by,
e.g., a large excess of electro-inactive salts (at the respective
potential), diffusion is normally regarded to be the dominant
mechanism. There are two components to the measured current,
a capacitive component resulting from redistribution of charged
and polar particles in the electrode vicinity and a component
resulting from the electron exchange between the electrode and
the redox species (analyte) termed faradaic current.20,24,97 The
faradaic component is the important measurand and is in case of
diffusion-limited conditions directly and linearly proportional
to the target analyte concentration.20,24
A picture and a schematic of a CMOS-based 3-electrode
voltammetric/amperometric sensor is shown in Fig. 8.100 The
monolithic device includes the electrochemical sensor, a
temperature sensor, and interface circuitry. The circuitry
contains an operational amplifier as potentiostat, a switchedcapacitor current-to-voltage converter and a clock generator.
Interface circuitry and temperature sensor are realized in 3 mm
CMOS technology.100 The circuit operates at a supply voltage
of 2.5 V, can apply voltages from +1 V to 21 V to the sensor
and handles current ranges from 30 nA full scale to 1 mA full
scale. The output voltage of the temperature sensor is
proportional to the absolute temperature and has a sensitivity of
125 mV K21. The total sensor dimensions are 0.75 3 5 mm.
Sensor processing sequences are given in refs. 97, 100, 101 and
102. The reference electrodes in liquid phase are in most cases
silver/silver chloride elements.
Typical applications include chemical analysis in gas or
liquid phase. Target analytes in the gas phase include oxygen101

Fig. 8 Micrograph (a) and layout (b) of a CMOS-based 3-electrode


amperometric sensor. Reprinted from ref. 100 with permission.

and carbon dioxide using liquid electrolytes.103 Target analytes


in liquid phase comprise dissolved oxygen,100,102,104 glucose,100,105107 or metal ions.108,109 If the target analyte is not an
electro-active species like the glucose molecules monitored
with the integrated system here, polymer electrolytes or
enzymes (glucose oxidase) producing analyte-related ionic
species are used in the sensitive electrode coatings.
4.4.2 Potentiometric sensors (chemotransistors). The most
important potentiometric sensors are based on the field-effect
transistor (FET), and are among the most intensively investigated chemical sensor devices (since 1970110). Field-effect
based transistors, which are the most common electronic
components on modern IC logic chips, rely on modulation of
the charge carrier density in the semiconductor surface spacecharge region through an electric field perpendicular to the
device surface: The source-drain current is controlled by an
isolated gate-electrode (see Fig. 1 and related text). In the
following we will describe the MOSFET (metal-oxide semiconductor field-effect transistor) for gas sensing applications
and the ISFET (ion-selective field-effect transistor) operating in
liquid phase.
The MOSFET (metal oxide semiconductor-FET) as used for
chemical gas sensing (Fig. 9) has a p-type silicon substrate
(bulk) with two n-type diffusion regions (source and drain). The
structure is covered with a silicon dioxide insulating layer on
top of which a metal gate electrode (electronics: poly-Si gate) is
deposited.
When a positive voltage (with respect to the silicon) is
applied to the gate electrode, electrons, which are the minority
carriers in the substrate, are attracted to the surface of the
semiconductor. Consequently, a conducting channel (n-channel) is created between the source and the drain, near the silicon
dioxide interface. The conductivity of this channel can be
modulated by adjusting the strength of electrical field between
the gate electrode and the silicon, perpendicular to the substrate
surface.
Palladium-(Pd)-gate FET structures were demonstrated to
function as a hydrogen sensor by Lundstrm et al.111 Hydrogen
molecules readily absorb on the gate metal (platinum, iridium,
palladium) and dissociate into hydrogen atoms. These H-atoms
can diffuse rapidly through the Pd and absorb at the metal/
silicon oxide interface partly on the metal, partly on the oxide
side of the interface.112,113 Due to the absorbed species and the
resulting polarization phenomena at the interface, the drain
current (Id) is altered and the threshold voltage (Ud) is shifted.
The voltage shift is proportional to the concentration or
coverage of hydrogen at the oxide/metal interface. Sensitivity
and selectivity patterns of gas-sensitive FET devices hence
depend on the type and thickness of the catalytic metal used, the
chemical reactions at the metal surface, and the device operation
temperature.
CMOS-based MOSFETs detecting hydrogen have been
described in refs. 114116.

Fig. 9 Schematic representation of a MOSFET and an ISFET structure. Ug


denotes the gate voltage, Ud the source-drain voltage. The ISFET is realized
by replacing the metal gate of the MOSFET with an ionic solution and a
reference electrode immersed into this solution.

MOSFET-sensor applications also include the detection of


ammonia,112,113 amines, and any kind of molecule that gives
rise to polarization in a thin metal film (hydrogen sulfide, ethene
etc.) or causes charges/dipoles at the insulator surface.112,113
In the case of the liquid-phase ISFET (ion-selective fieldeffect transistor), the gate metal electrode of the MOSFET is
replaced by an electrolyte solution, which is contacted by the
reference electrode. The gate oxide is directly exposed to the
aqueous electrolyte solution (Fig. 9).110 An external reference
electrode is required for a stable operation of an ISFET.20,24,97
The sourcedrain current is influenced by the potential at the
oxide/aqueous solution interface. ISFET amplifiers with feedback keep the sourcedrain current constant by compensating
solution-induced changes in the gate oxide potential by
modulation of the gate voltage (Ug) that is applied to the
reference electrode. The gatesource potential is then determined by the surface potential at the insulator/electrolyte
interface. Mechanistic studies of the occurring processes at the
solution/gate oxide interface (site binding model117) and the
oxide semiconductor interface can be found in literature.20,24,97,117119 The insulator solution interface is assumed to
represent in most cases a polarizable interface, i.e., there will be
charge accumulation across the structure but no net charge
passing through.
Classic ISFET applications include pH-sensing (acidity or
basicity) with an exposed-gate-oxide FET.110 The surface of the
gate oxide contains OH-functionalities, which can be protonated and deprotonated and thus, when the gate oxide contacts
an aqueous solution, a change of pH will change the silicon
oxide surface potential.110,120 Typical pH-sensitivities measured with silicon oxide ISFETs are 3740 mV per pH unit.121
Gate materials such as silicon nitride,122130 oxynitride,131 or
alumina132134 have better properties than silicon oxide with
regard to pH-response, hysteresis and drift. In practice, these
layers are deposited on top of the silicon oxide by means of
chemical vapor deposition (CVD).
ISFETs can also be covered with organic ion-selective
membranes like polyurethane, silicone rubber, polystyrene, and
polyacrylates containing ionophores to detect metal ions such as
potassium,135,136 sodium137 or silver.138 Cell metabolism
induced pH-changes have been monitored,128 and glucose has
been detected using a proton-producing electrochemical reaction.130
The fabrication of CMOS integrated field-effect-based
electrochemical sensors with circuitry is described in various
publications.97,122131,139 An example of an integrated ISFET is
shown in Fig. 10a.131
The system includes an ISFET amplifier (source and drain
follower) and two interdigitated ISFETs realized in a 1.0 mm,
two-metal CMOS process (Atmel-ES2, Atmel, France). The pH

Fig. 10 (a) Micrograph of a CMOS chip hosting two integrated ISFETs


and an ISFET amplifier. (b) Schematic and cross-section of the ISFET. For
details, see text and ref. 131. Reprinted from ref. 131 with permission.

Analyst, 2003, 128, 1528

21

measurements have been conducted using a Ag/AgCl reference


electrode and yielded a sensitivity of 47 mV per pH unit using
silicon oxynitride as the pH-sensitive material.131 To render the
fabrication CMOS-compatible, the sensitive oxynitride sits on
top of an electrically floating multi-conductor gate structure
including the two metal layers and the gate polysilicon, all of
which are electrically connected (Fig. 10b). This way, the pHdependent electrical charge at the surface of the oxynitride in
contact with the solution directly affects the silicon surface
sourcedrain current (Fig. 10b).131
4.4.3 Conductometric sensors. Conductometric techniques
are a special case of alternating-current (AC) impedance
techniques. Instead of the real and imaginary component of the
electrode impedance at different frequencies, only the resistive
component, related to the sample (sensing material) resistance
is of interest. Since complex impedances include capacitive and
inductive contributions, chemocapacitors are included here, in
the conductometric section. The section on conductometric
sensors is hence organized in two subsections, one on
chemoresistors and the other subsection on chemocapacitors.
4.4.3.1 Chemoresistors. Chemoresistors rely on changes in
the electric conductivity of a film or bulk material upon
interaction with an analyte. Chemoresistors are usually arranged
in a metal electrode 1/sensitive layer/metal electrode 2 configuration.20,21,24 The resistivity/conductance measurement is
done either via a Wheatstone bridge arrangement or by
recording the current at an applied voltage in a DC (direct
current) mode or in a low-amplitude, low-frequency AC
(alternating current) mode to avoid electrode polarization. The
contact resistance should be much lower than the sample
resistance and be minimized, so that the bulk contribution
dominates the measured overall conductance.
There is two major classes of chemoresistors: (1) hightemperature chemoresistors (200600 C) with semiconductor
metal oxide coatings and (2) low-temperature chemoresistors
(room temperature) with polymeric and organic sensitive
coatings. We will focus on the technologically more challenging high-temperature sensors and only briefly mention the
second type with the applications.
The sensitive materials used with high-temperature chemoresistors include wide-bandgap semiconducting metal oxides
such as tin oxide, gallium oxide, indium oxide, or zinc oxide, all
of which can only be operated as sensing materials at high
temperature ( > 200 C). In general, gaseous electron donors
(hydrogen) or acceptors (nitrogen oxide) adsorb on the metal
oxides and form surface states, which, at high temperature, can
exchange electrons with the semiconductor. An acceptor
molecule will extract electrons from the semiconductor metal
oxide and thus decrease its conductivity. The opposite holds
true for an electrondonating surface state. The reaction
between gases and oxide surface depends on the sensor
temperature, the gas involved, and the sensor material.20,140144
Semiconductor metal oxide sensors usually are not very
selective, but respond to almost any analyte (carbon monoxide,
nitrogen oxide, hydrogen, hydrocarbons). One method to
modify the selectivity pattern includes surface doping of the
metal oxide with catalytic metals such as platinum, palladium,
gold, and iridium.20,21,140144
The device requirements for a high-temperature chemoresistor include a thermally well-isolated stage such as a
membrane, which allows for keeping the sensing materials at a
high temperature without heating the bulk chip (protection of
electronic components), an integrated heater, and a temperature
sensor (Fig. 11).145,146
Fig. 11 shows a front-side-etched microhotplate on a CMOS
substrate.145,146 The microhotplate components include a
polysilicon resistive heater, an aluminum metal plate for heat
22

Analyst, 2003, 128, 1528

distribution and temperature measurement and four noble


metal-coated aluminum or tungsten contacts for electrical
connection to the sensing film.145,146 Tin dioxide is then
deposited on top of the metal electrodes.
Since microhotplates have a very low thermal mass, they
allow for applying temperature-programmed operation modes,
which enhance the gas detection capability.147,148
The fabrication of hotplates on CMOS-substrates is described
in refs. 145, 146, 149 and 150. Complete processing sequences
are detailed in refs. 150 and 151. First results with hotplates and
circuitry on a single CMOS-chip have been presented recently.152,153 Multi-chip solutions have been proposed in refs.
154 and 155. Reliability tests with CMOS hotplates have been
conducted.156 CMOS-hotplates realized on SOI (silicon on
insulator) and SIMOX (separation by implantation of oxygen)
substrates are presented in refs. 157 and 158.
Typical microhotplate applications include the detection of
inorganic gases such as hydrogen,145,146,150 oxygen,145,146
nitrogen oxide,147,159 carbon monoxide,145148,155,159 and a
variety of organic volatiles145,146,150,159161 using predominantly tin oxide as sensitive layer.
Several classes of predominantly organic materials are used
for application with chemoresistors at room temperature
(electrode spacing typically 5 to 100 mm, applied voltage 15
V). Conducting polymers such as polypyrroles, polyaniline and
polythiophene are used to monitor a variety of polar organic
volatiles like ethanol, methanol, and components of aromas.162165 Conducting carbon black can be dispersed in nonconducting polymers so that if the polymer absorbs vapor
molecules and swells, the particles are, on average, further apart
and the conductivity of the film is reduced (conductivity by
particle-to-particle charge percolation).166 Applications also
include organic solvents such as hydrocarbons, chlorinated
compounds, and alcohols.166170
CMOS-based monolithic sensor systems coated with carbon
black/polymer blends are detailed in,169,170 two-chip solutions
with a CMOS circuitry chip and a separate sensor chip based on
conducting polymers can be found in refs. 164 and 165. A
CMOS-compatible monolithic conductivity sensor for liquid
phase (Pt electrodes) was presented in ref. 171.
4.4.3.2 Chemocapacitors. Chemocapacitors (dielectrometers) rely on changes in the dielectric properties of a sensing
material upon analyte exposure. Interdigitated electrode structures are predominantly used.172,173 The capacitances usually
are measured at an AC frequency of a few kHz up to 500
kHz.
The interdigitated capacitors described here exhibit an
electrode width and spacing of 1.6 mm. The total footprint of a
capacitor is 800 3 800 mm2. Since the nominal capacitance of
such a microstructure is on the order of 1 pF and the expected
capacitance changes (sensor signals) in the range of some
attoFarads, an integrated solution with on-chip circuitry is

Fig. 11 Scanning electron micrograph of a microhotplate. The suspended


plate exhibits a polysilicon heater, an aluminum plane for homogenous heat
distribution and noble metal-coated aluminum electrodes for measuring the
resistance of a semiconductor metal oxide. Reprinted from refs. 145 and 146
with permission.

required. There is no possibility to transfer such minute analog


signals via bond wires and cables to desktop instruments. The
integrated solution includes two capacitors, a polymer-coated
sensing capacitor and a silicon nitride-passivated reference
capacitor in a switched-capacitor scheme (Fig. 12). The sensor
response is read out as a differential signal between the
polymer-coated sensing and a passivated reference capacitor. A
digital output signal is then generated by comparing the minute
loading currents of both capacitors using a fully differential
second-order SigmaDelta-modulator circuitry.174,175 A
counter to decimate the output bit stream is co-integrated onchip. A schematic of a capacitive chemical sensor microsystem
is shown in Fig. 12.
Two effects change the capacitance of a polymeric sensitive
layer upon absorption of an analyte: (i) swelling and (ii) change
of the dielectric constant due to incorporation of the analyte
molecules into the polymer matrix.46,174,176 The capacitance
change for a polymer layer with a thickness of approximately
half the periodicity of the electrodes is determined by the ratio
of the dielectric constants of analyte and polymer. If the
dielectric constant of the polymer is lower than that of the
analyte, the capacitance will be increased. Conversely, if the
polymer dielectric constant is larger, the capacitance will be
decreased (see Fig. 15 later). These effects have been further
discussed and supported by simulations in ref. 176.
For conducting measurements at defined temperatures,
sensor and reference capacitors can be placed on thermally
isolated membrane structures.175
The fabrication of capacitors integrated with CMOS circuitry
components is described in refs. 46, 173178.
Typical applications include humidity sensing with polyimide films,172,173,177179 since water has a high dielectric
constant of 78.5 (liquid state) at 298 K leading to large
capacitance changes. CMOS-based integrated capacitive humidity sensors are commercially available from, e.g., Sensirion
AG, Switzerland.180 More recent applications also include the
detection of organic volatiles in the gas phase using polymeric
layers.46,174176
4.5 Monolithic integration of different transducers
Another significant advantage of CMOS-based chemical sensors is the possibility to integrate several different transducers
along with all the driving circuitry on a single chip. Additional
components that can be integrated include signal conditioning
circuitry (amplifiers, references), multiplexers to reduce the
number of output pins, analog/digital and digital/analog converters, chip memory (calibration values) or other smart
features, an intra-chip communication or bus system and a serial
interface to communicate with off-chip microcontrollers or
instruments. In the following we will present two prototype
monolithic CMOS multisensor systems, (1) a multiparameter

Fig. 12 Schematic of a capacitive chemical sensor microsystem including


a polymer-coated sensing capacitor and a Si-nitride-protected reference
capacitor. The on-chip circuitry includes a SD-converter.

biochemical sensor181 and (2) smart gas sensor microsystem.182


4.5.1 CMOS multiparameter biochemical microsensor181.
The microsensor system is aimed at continuous monitoring of
ions, dissolved gases and biomolecules in liquid phase such as
blood (Fig. 13),181,183 and is based on an earlier design by
Gumbrecht et al.184 The eight integrated chemical sensors
comprise six ion-sensitive field-effect transistors (ISFETs: 16
in Fig. 13), one oxygen sensor (7 in Fig. 13) and one
conductometric sensor (8a,b in Fig. 13), all of which can be
operated in parallel.181 An Ag/AgCl reference electrode was
also integrated on the CMOS chip to get rid of external
references. A flow channel (polyimide) restricts the liquid phase
access to the sensor area.
The six ISFETs allow for direct contact of the electrolyte with
the gate oxide. The gate oxide itself is pH-sensitive (see ISFET
section), or the ISFET can be used as a Severinghaus-type pHFET to measure dissolved carbon dioxide (detection of carbon
dioxide via dissolution in water, formation of carbonic acid
and monitoring of the pH change). The gate oxide can also be
covered with different ion-selective membranes to achieve
sensitivity to a range of target ions such as potassium. All six
ISFETs or only a subset can be used. The idea is to make a
standard chip to reduce manufacturing costs and then modify
the chip with selective coatings according to user needs.
The integrated amperometric sensor can be used as a Clarktype oxygen sensor, which is based on a two-step-reduction of
gaseous oxygen in aqueous solution via hydrogen peroxide to
hydroxyl ions.
The conductometric sensor consists of two parallel sensors
(8a), which share one common electrode (8b). A sinusoidal AC
potential is applied to the electrodes, and the current, which
depends on the solution composition (concentration of charged
particles or ions) is recorded. The eight sensors can continuously monitor ions, dissolved gases and biomolecules via
enzymatic reactions that produce charged particles.
The full system is produced in a 1.2 mm single-metal, singlepoly CMOS process and the chip size is 4.11 3 6.25 mm.181 The
chip is operated at 5 V and hosts all driving circuitry for the
sensors such as ISFET buffer amplifiers, a potentiostatic setup
for the amperometric sensor and the circuitry necessary to
perform a four-point conductometric measurement on chip. In
addition the chip exhibits a temperature control unit to keep the
system temperature at an adjusted value (physiological conditions). This temperature control unit includes a temperature

Fig. 13 Micrograph of the CMOS multi-parameter biochemical sensor


chip, which includes 6 ISFETS (16), one conductometric sensor (8a,b) and
an (amperometric) oxygen sensor (7). The on-chip circuitry includes an
EPROM, a multiplexer and counter, a driver unit, a conductometric and
potentiostatic circuit and a heater. Reprinted with permission from ref.
181.

Analyst, 2003, 128, 1528

23

sensor (parasitic vertical pnp bipolar transistor) and a NMOS


transistor heater. A single-bit EPROM (electrically programmable read-only memory) was implemented on chip to make
sure the chip is only used once and then is disposed, which is a
crucial feature in medical applications. Additional on-chip
electronics include units to control the chip (multiplexer,
demultiplexer, 4-bit Gray counter and decoder) and units to
provide the biasing and the communication to off-chip instrumentation. Due to the high level of on-chip integration only
5 external connections are needed: two for power supply, two
for bi-directional communication and one for a clock signal.
First tests including amperometric oxygen measurements, the
assessment of potassium concentrations with ISFETs, and
conductometric measurements with a buffer solution have been
performed.181
4.5.2 CMOS single-chip gas sensor microsystem182. The
CMOS single-chip chemical microsensor system combines
three different transducers, a mass-sensitive cantilever, a
capacitive sensor, and a calorimetric sensor, all of which rely on
polymeric coatings as sensitive layers to detect airborne volatile
organic compounds (VOCs). The three transducers respond to
fundamentally different analyte molecule properties. One of
them responds to the mass of sorbed molecules, another
responds to the heat of absorption, and the third responds to the
dielectric properties of the absorbates. The monolithic system
such simultaneously provides three different (orthogonal)
sensor responses, which are used to classify or quantify analytes
in the gas phase.
The capacitive sensor as previously described in section
4.4.3.2 is integrated with a fully differential second-order
Sigma-Delta-modulator circuitry and a counter to decimate the
output bit stream.185
The micromachined cantilever, the operation principle of
which has also been already described in section 4.1.2, is 150
mm long and consists of silicon as well as vapor-deposited and
thermal oxide. The cantilever acts as the frequency-determining
element in a feedback oscillation circuit, which is entirely
integrated on the chip with a counter. For more details on the
electronics, see refs. 43 and 185.
The third transducer is a thermoelectric calorimeter based on
the Seebeck effect with 256 polysilicon/aluminum thermocouples connected in series (500 mm by 500 mm dielectric
membranes). Details have been described in section 4.2.2. The
thermovoltage is translated into a digital signal on chip using a
SigmaDelta analog/digital converter and a decimation filter.
The overall system chip additionally includes a temperature
sensor since volatile absorption in polymers is strongly
temperature-dependent. The temperature sensor relies on the
linear temperature dependence of a bipolar transistor available
in the CMOS process. The voltage is converted to a digital
signal using a SigmaDelta converter. After calibration, the
temperature sensor exhibits an accuracy of 0.1 C at operation
temperatures between 240 and 80 C.
A micrograph of the microsystem chip is displayed in Fig. 14.
The overall chip size is 7 3 7 mm. The chip exhibits all the
sensor-specific driving circuitry and signal-conditioning circuitry, which has been described in the context of the different
transducers. The analog/digital conversion is done on chip,
which allows for achieving a favorable signal-to-noise ratio,
since noisy connections are avoided and a robust digital signal
is generated on chip and then transmitted to an off-chip data port
via an I2C serial interface.186 The I2C bus interface offers the
additional advantage of having only very few signal lines
(essentially two) for bi-directional communication and also
allows for operating multiple chips on the same bus system. An
on-chip digital controller manages the sensor timing and the
chip power budget. The sensors are located in the center of a
metal frame, which is used to apply a flip-chip packaging
technique.187
24

Analyst, 2003, 128, 1528

Fig. 15 displays simultaneously recorded sensor signals of all


three transducers upon exposure to 1200 and 3000 ppm (parts
per million) of ethanol, and 1000 and 3000 ppm of toluene at 30
C.181,185 The sensors were alternately exposed to analyte gas
and pure carrier gas. The polymeric coating consisted of
poly(etherurethane), PEUT46 at a thickness of approximately 4
mm.
Fig. 15a shows the measured frequency signals (SigmaDelta
converter output) of the capacitor. Ethanol exhibiting a
dielectric constant of 24.5, which is larger than that of PEUT
(2.9), causes a capacitance increase and hence positive
frequency shifts, toluene with a dielectric constant of 2.4 causes
a capacitance decrease and negative frequency shifts. Fig. 15b
displays the cantilever response. The resonance frequency
decreases with increasing oscillating mass as a consequence of
volatile absorption. Ethanol shows rather low signals as
compared to toluene due to its lower molecular mass and due to
its lower enrichment (partitioning) in the polymeric phase.
The calorimetric results in Fig. 15c represent a superposition
of already discussed partitioning and heat budget change due to
analyte ab/desorption. The absorbing analyte liberates heat
(heat of condensation) causing a positive transient signal
(positive peak), whereas the desorbing analyte abstracts vaporization heat from the environment generating a negative
transient signal (negative peak upon purging, see Fig. 15c). The
close-up in the upper left corner shows the time-resolved
response upon 3000 ppm of toluene within the first 6 s.
The signals of all three transducers linearly correlate with
analyte concentration at low concentrations (less than 3% of
saturation vapour pressure at the operating temperature). To
further improve analyte identification/quantification, an array
of microsystem chips coated with different polymers can be
used. The monolithic CMOS gas microsystem is targeted at
identifying organic solvents in transport containers or providing
workplace safety in, e.g., chemical industry. It will form part of
a handheld or credit card size detection unit.

5 Outlook
The field of CMOS-integrated chemical sensors is currently
expanding as can be seen from the growing number of
publications in the last years. As can be concluded from the
article, the research and development thrusts go in the direction
of integrating more and more electronic functions on the sensor
chip such as adaptive circuits for signal evaluation and
discrimination,188,189 or telemetry units for wireless communication. Telemetry functions will encompass, e.g., communication from implanted chips (glucose sensors) through the

Fig. 14 Micrograph of the gas microsensor system chip (size: 7 3 7 mm).


The different components include: (1) flip-chip frame, (2) reference
capacitor, (3) sensing capacitor, (4) calorimetric sensor and reference, (5)
temperature sensor, (6) mass-sensitive resonant cantilever, and (7) digital
interface. Reprinted with permission from ref. 182.

Fig. 15 Sensor signals simultaneously recorded from all three polymer-coated transducers upon exposure to 1200 and 3000 ppm of ethanol and 1000 and
3000 ppm of toluene at 301 K: (a) frequency shifts (SigmaDelta converter output) of the capacitor, (b) frequency shifts of the resonating cantilever, and (c)
thermovoltage transients of the calorimetric sensor. The close-up shows the development of the calorimetric transient within 6 s. Reprinted with permission
from ref. 182.

skin in medical applications190 or the transmission of remote


and distributed chemical sensor responses to a central terminal
in environmental and building control scenarios by using radio
frequencies191193 or other standards like Bluetooth.194
Another extensively belabored field of research will target
the combination of CMOS chips with biomaterial such as living
cells or neurons. Portable, cell-based biosensor systems with
CMOS chips have been reported on by Kovacs and coworkers.195,196 The interfacing of neurons or nerve ends with CMOS
circuitry to develop neural probes,197199 neuromuscular microstimulators,200 or neural prostheses is at an early stage but will
gain momentum and will most probably also include monitoring
of chemical parameters (ionic signals have to be translated into
electronic signals). Sensor arrays for DNA-analysis based on
CMOS-assisted electronic detection rather than optical detection may also constitute an interesting application for CMOS
technology.201,202
In summary, CMOS and CMOS-MEMS technology and
processes offer a great deal of readily available electronic
circuits provided by the huge development efforts of the ICindustry, only a small fraction of which has been used for
chemical sensors so far. It has to be kept in mind, however, that
CMOS sensor development is expensive (mask and processing
costs) and only pays off, if either millions or at least hundreds
of thousands of pieces are sold, or if the devices provide unique
functionality, which then makes up for the costly development.
The killer-applications involving large numbers of chemical
sensors have not emerged yet. They may be in the field of
automotive applications, domestic gas alarms, HVAC (humidity, ventilation, air conditioning) units, or in the field of
disposable medical devices (e.g., DNA or blood tests).

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6 Acknowledgements

22

The authors are greatly indebted to current and former staff of


the Physical Electronics Laboratory at ETH Zurich involved in
the chemical microsensor development, notably Christoph
Hagleitner, Dirk Lange, and Oliver Brand.

23

7 References

24
25
26
27
28

A. Van den Berg, P. D. van der Waal, B. B. van der Schoot and N. F.
de Rooij, Sens. Mater., 1994, 6, 2343.
2 G. Mller, P. P. Deimel, W. Hellmich and C. Wagner, Thin Solid
Films, 1997, 296, 157163.
3 G. T. A. Kovacs, Micromachined Transducers, MCB McGraw-Hill,
New York, 1998.

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