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Biosensors and biodiagnostics is a rapidly growing field, where the use of micro/nano technologies promises breakthrough advancements in sensitivity and sample volume requirement. Illustrative examples of CFDRC’s work in this area are provided below:
Nanofluidic Biosensor: CFDRC is developing a novel nanofluidics-based biosensor system for the detection and quantification of biological threat agents. The system features recently discovered nanoscale phenomena of charge exclusion assisted valence and mobility manipulation of analytes of interest. In nanofluidic systems, enhanced surface electrostatic effects result in the formation of an electric double layer (EDL) that extends into a considerable portion of the channel. The presence of a “thick” EDL is used to exclude or focus the analytes that have a charge with the same polarity as the channel surface. These phenomena, not attainable in microfluidic/capillary systems, are harnessed for separation and preconcentration of the target analytes. The nanofluidically processed sample is then presented to a functionalized Carbon NanoTube (CNT) based platform for detection and quantification.
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Nanofluidic Biosensor Development. |
CV of GOx/CNT Modified (Blue) and GC (Pink) Blank Electrodes. |
Optical Biosensor
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Optical biosensors based on Surface Plasmon Resonance (SPR) and
fluorescence detection are commonly used in lab-on-a-chip devices.
SPR-based sensors can provide real-time kinetic data on DNA hybridization
and specific biochemical binding reactions without labeling requirements.
CFDRC engineers have developed software to design (a) the geometric
design of biosensors, and (b) a detailed assay protocol. The software
can be used to determine optimal placement of sensor patches, optimal
values for the sample volume, flow rate, and wash step.
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Click for animation
Computational Model of a Biacore™
Flow Cell Showing Analyte Distribution
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Time Response of a Biacore™ SPR Sensor
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Electrochemical Sensing
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Electrochemical biosensors use electrochemical methods for transduction.
They can be subdivided in to three types:
- Potentiometric sensors that involve the measurement of potential
of a cell at zero current. The potential will be proportional
to the logarithm of the concentration of the substrate being measured.
- Amperometric sensors where an increasing (decreasing) potential
is applied to the cell until oxidation (reduction) of the substance
to be analyzed occurs. This results in sharp rise (decrease) in
the cell current to give a peak current. The height of this peak
current will be directly proportional to the concentration of
the electroactive species.
- Conductimetric sensors use the relationship between the conductance
and ionic species concentration to measure the concentration of
the substrate.
Our simulation technology has the capability to simulate various
biosensors using the Flow, Heat, Chemistry and Electric modules.
Such simulations help designers optimize sensors in terms of process
conditions, selection of buffer pH, membranes, and cell geometry,
among others. Most of this smulation technology has been incorporated
into the CFD-ACE+ software.
The sample problem shown demonstrates how CFDRC engineers optimized
an oxygen biosensor that works on the amperometric method. Simulations
have been performed to quantitatively estimate how the signal varies
with oxygen concentration, as well as to understand the more complex
phenomenon of sensitivity of the assay due to variations in the
diffusivity of the oxygen caused by Joule heating.
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Schematic of a Typical Oxygen Biosensor
(Courtesy: University of Cincinnati)
Predicted Peak Current As a Function of Oxygen Concentration in
the Blood Sample
Influence of Joule Heating on Induced Current Density
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Enzymatic Biosensor
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Enzymatic biosensors utilize the biospecificity of an enzymatic
reaction, along with an electrode reaction that generates an electric
current or a potential difference for quantitative analysis. The
upper figure shows the configuration of an electrochemical glucose
sensor operating in the stopped flow mode. The enzymatic oxidation
of glucose produces hydrogen peroxide, which in turn generates electrons
by electrode reaction. The current density is used as a measure
of glucose in the sample.
Our technology can be used for the design of enzymatic sensors
as well as to investigate effects such as Joule heating and electrode
geometry in order to minimize sensor response time and maximize
signal produced.
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