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A G R E AT E R M E A S U R E O F C O N F I D E N C E substance (analyte)
3. Combine an electrical interface (trans-
ducer) with the biologically sensitive and
selective element
More specifically, a biosensor contains
a bioreceptor, which is a biomolecule that
recognizes the target analyte. The trans-
Biosensor/transducer
ducer portion of the biosensor converts the
recognition event into a measurable signal
that correlates with the quantity or presence
qualification:
of the chemical or biological target that can
cause physiological damage. A generalized
biosensor model is illustrated in Figure 1.
a critical step for Performance criteria for a biosensor sys-
tem include:
homeland security
1. Speed and ease of use (testing/calibra-
tion/maintenance) by non-technical per-
sonnel
2. Selectivity (to target analyte)
3. Sensitivity/resolution
4. Accuracy/repeatability
Jonathan Tucker, Keithley Instruments, Inc. 5. Dynamic range (high analyte concentra-
tions will not degrade sensor usability)
6. Environmentally robust (relatively in-
Mounting a defense against bioterroism here defined as devices that do one or more of the sensitive to temperature, electrical noise,
at home, and protecting soldiers on the bat- following: physical shock, vibration, etc.)
tlefield from chemical and biological war- 1. Detect, record, convert, process, and 7. Usable lifetime/adaptability
fare agents requires fast, reliable environ- transmit information regarding a physi- 8. Safety/integrity (for personnel, equip-
mental sensors that provide early detection ological change or process ment, and analytes)
of these threats. Accurate characterization 2. Utilize biological materials to monitor Current biosensor systems can accurately
of new sensor designs can speed up devel- the presence of various chemicals in a recognize organic chemicals and microbes
opment, and instrument manufacturers can
provide valuable insight on how it's done.
M
ANY sensors, transducers,
and detection systems are
being investigated for defen-
sive applications. They vary
greatly in their complexity
and the amount of time it takes to get results.
Biosensor/transducer technologies that gen-
erate electrical outputs offer numerous ad-
vantages in the design of detection systems
to meet speed and ease of use criteria. With
proper testing and calibration, electronic
biosensors can meet these criteria while pro-
viding reliable results that minimize false
positive and negative indications.
Current Biosensor Designs
The focus of this article is on electronic
biosensor/transducer units that can be used
in bioterrorism defensive systems, and the
electrical characterization of these sensors.
Hereafter, biosensor/transducer units are re-
ferred to simply as biosensors, and they are Figure 1. Representation of a generic biosensor.
Biosensor/transducer qualification: a critical step for homeland security March 2004 1
utilizing various receptor technologies. For gens bind to the receptor housed in the liquid rimetric, fluorescent or luminescent indica-
toxic airborne gases, inorganic sensor mate- crystal matrix. tors. Sometimes, an optical fiber is used for
rials such as tin oxide, gold, platinum, and Multiple technologies can be combined guiding light signals from the source to the
semiconductors are used. For microbes in to create biosensors with different perfor- detector.
liquid analytes (blood samples, etc.) bio- mance characteristics. These include nucleic
receptors such as enzymes, antibodies and acid probes, PCR-amplified nucleic acid re- Sensor Characterization: First Step
nucleic acids are used. Chemical sensors for actions, various enzyme-linked immunosor- in Validation Process
toxic gases can react quickly to their selected bant techniques, and many others. Some sen- Development programs are aimed at
targets and provide a convenient electrical sors designed around biologically engineered overcoming design limitations in current
output. However, few commercial biosensor molecules may surpass the limits of binding biosensor systems. For example, one of the
designs that utilize enzyme receptors, anti- measurable by other methods. Still, most of problems in biosensor design is achieving
gen-antibody reactions, ligand (DNA/RNA) these devices trade off speed for sensitivity or a stable, reproducible interface between the
binding, or whole cell metabolism can rap- lower cost. Typically, they require upwards of biological affinity elements and an inorganic
idly and automatically provide a high-level 10,000 organisms for detection, and may also transducer element. The desire to miniatur-
signal. require highly skilled operators. ize biosensors for handheld portability, and
Depending on the analyte and biorecep- still achieve adequate sensitivity, imposes
New Sensor Designs tor, the transducer portion of a biosensor significant technical challenges in the cou-
For faster detection with a readable elec- could utilize one of the following mecha- pling of biomolecules to transducer surfaces.
trical output, researchers are developing bio- nisms: Therefore, fast and accurate electrical char-
sensors that combine these or similar func- Amperometric: Amperometric devices acterization of biosensors in the development
tions with semiconductor devices in compact detect changes in current. They measure lab and in production is essential for qualify-
portable units for field use. One approach currents generated when electrons are ex- ing the sensor/transducer interface, and the
uses an oligonucleotide sensor and nucleic changed between a biological system and an ultimate operation of a biodetection system.
acid reaction to indicate the presence of a electrode. A typical test program task is develop-
pathogen. Another design employs surface Potentiometric: Some reactions cause a ing or verifying performance metrics for
plasmon resonance (SPR) to detect biologi- change in voltage (potential at constant cur- the biosensor. Because of the complexity in
cal molecules such as protein and DNA. One rent) between electrodes that can be detected extracting cell and tissue signatures of agent
SPR-based sensor reportedly provides label- or measured. activity and response, it is often desirable to
free studies of molecular interactions in real Conductive: Conductimetric devices conduct direct current-voltage (I-V) char-
time. It has a sensor chip interface that fa- detect changes in conductivity between two acterization on key components of the bio-
cilitates attachment of specific ligands to the electrodes. sensor. I-V characterization requires only a
transducer surface, and provides a sensitive Resistive: Resistivity is the inverse of small fraction of the time needed for most
measurement of surface concentrations. conductivity, and can be measured with sim- types of functional testing, but is a powerful
Tissue-based sensors are also being de- ilar methods. predictor of full fledged operation. For exam-
veloped. They utilize living cells on chips Capacitive: When the biorecognition ple, I-V data can be used to study anomalies,
that can react functionally to the presence of reaction causes a change in the dielectric locate maximum or minimum curve slopes,
both biological and chemical threat agents. constant of the medium in the vicinity of the and perform reliability analyses. Depending
Because they are designed to mimic the bioreceptor, capacitance measurement meth- on design specifics, I-V characterization is
function of multi-cellular human tissue, od can be used as a transducer. often suitable for sensors based on ampero-
these sensors should respond to both known Piezoelectric: In a piezoelectric material metric, potentiometric, conductive, resistive,
and previously uncharacterized agents. The there is a coupling between its mechanical and thermal principles.
transducer senses small changes in electrical and electrical properties. It can be used to Usually, I-V testing applies a voltage or
charges on the surface of the living cells. create an electrical oscillator whose frequen- current to the device under test (DUT), and
A developmental liquid crystal detection cy can be varied and measured by varying a measures its response to that stimulus. Tem-
system has been demonstrated that can se- mass applied to its surface. In the case of a perature measurements may also be taken.
lectively identify pathogens in only minutes. biosensor, that mass can change due to the The test procedures may involve probing of
The liquid crystals amplify antibody struc- reaction taking place on the surface. integrated circuits to apply the stimulus to
tural changes that are induced by antigen- Thermal: These devices measure chang- certain connections pads, and measure the
antibody binding. A change in the heavy es in temperature. DUT response on others.
molecular chain deforms the liquid crystal Optical: Optical biosensors correlate Depending on the DUT, signal levels
array alignment. Through the use of polar- changes in concentration, mass, or number may be quite low. This calls for highly sen-
izing filters, light transmission through the of molecules to direct changes in the char- sitive source and measurement instruments,
liquid crystal cells is altered. This change acteristics of light. For this method to work, and test techniques that minimize external
can be converted to an electrical signal that one of the reactants or products of the bio- sources of error. Where an optical mecha-
alerts personnel when pathogenic agent anti- recognition reaction has to be linked to colo- nism is involved, I-V characterization may
2 March 2004 Biosensor/transducer qualification: a critical step for homeland security
also involve simultaneous measurements of voltmeter should be considered instead of a nanovoltmeters, which minimize electrical
the wavelength or intensity of a light output data acquisition board or DMM solution. A noise from AC lines, and from random noise
with a photodetector. This is called L-I-V nanovoltmeter is a very sensitive digital volt- sources. These techniques are less likely to
testing. meter with an A/D resolution in the 20-24 bit be available in PC-based data acquisition
range. This type of instrument is optimized systems, but knowledgeable users can pro-
Characterizing the Performance of for accurate, low level voltage measurements, gram a system for signal averaging to help
Biosensors even when the signal is approaching the reduce external noise.
In many cases, biosensors used by medi- theoretical (lower) limit associated with sen- Current measurements. Amperometric
cal practitioners, military personnel, and sors having a low output impedance. (Low sensors require a different characterization
public safety forces will be part of a portable output impedance requires a voltmeter with approach. Electrical currents can be mea-
system. This places restrictions on the sen- a high input impedance to avoid measure- sured with data acquisition systems, but the
sors' operational power requirements, and ment errors.) Although the input impedance method selected will depend on the current
may dictate the level of voltage or current of a nanovoltmeter is similar to a DMM, it level and number of required measurement
output that can be provided to measurement has much lower voltage noise and drift. This channels. Otherwise, I-V characterization of
circuitry. In battery operated systems, sen- gives the nanovoltmeter much better voltage a current loop sensor system is uncomplicat-
sor output current can range from nanoamps sensitivity