|Professor Joseph J. BelBruno, Department of Chemistry,
Dartmouth College, Hanover, NH 03755 USA. Corresponding author: [email protected]
Molecular recognition and molecular encapsulation are nanoscale
processes that offer great potential for applications as diverse as
sensors, environmental remediation and targeted drug delivery.
Biological receptors and natural materials such as liposomes offer
excellent characteristics for such uses. However, these molecules are
expensive, complex to produce and are sensitive to chemical and
physical environments. Molecular imprinting produces molecule-specific
cavities that mimic the behavior of, and may be substituted for,
natural receptor binding sites or antibodies, without the temperature
sensitivity and high cost of the natural systems.1
Moreover, these artificial receptors may be synthesized for almost any
While several alternative methods exist, the general concept for
imprinting, via polymerization, is displayed in Figure 1. The
template or target molecule is mixed with monomer. Through
self-assembly, the template forms a complex with the functional groups
of the monomer. The self-assembled structure is locked into place by
polymerization with a crosslinking agent. After polymerization is
complete, the template is extracted from the polymer and the
molecularly imprinted polymer or MIP is ready for use. The MIP
selectively rebinds the template molecule from solution or from the
Figure 1. The synthetic
procedure for production of MIPs is shown. The template and
monomer are mixed and a pre-polymerization complex is formed.
Crosslinker and initiator are added and the complex is “locked” into
the polymer. Finally, the template is removed and the MIP is
ready for rebinding.
When coupled to a technique that reads out the presence of the
analyte, MIPs provide a molecularly specific method of identifying a
chemical agent. Molecularly imprinted polymers have been used as solid
phase extraction adsorbents and as chromatographic (GC and HPLC) column
materials for the separation and determination of a range of targets
including environmental contaminants, pharmaceuticals, pesticides,
chemical warfare materials and industrial waste streams. Drug
detection and drug delivery are additional research fields in which
MIPs may play a role.1 Both larger
biological molecules as
such as proteins and smaller, commercial therapeutics have been
The formation of MIPs is often characterized by significant
changes in polymer morphology, which are observed using microscopy
techniques on the nanoscale.2 Figure 2
force microcopy (AFM) images of our unimprinted and glucose-imprinted
polyvinylphenol polymers. Note that the pores created in the
imprinted polymeric material are of the order of a few tens of
The formation of the film is controlled by the
relative phase separation of the template-polymer host complex from the
other components, template-template and polymer-polymer, of the MIP
solution. These are images of a thin film of the MIP, with a measured
thickness of ~300nm.
Figure 2. AFM images of an
unimprinted polyvinylphenol film (left) and a polyvinylphenol film
imprinted with glucose (right).
MIPs are of interest as synthetically formed recognition and binding
agents for a variety of sensing applications, which are the focus of
our current research. As sensors, the key elements of MIPs are the
density of active sites, their geometric accessibility governing sensor
response speed, and the selectivity they exhibit for the analyte. Thin
film materials rather than powders may be used to optimize the density
and availability of receptor sites, as they are often formed under
non-equilibrium conditions, and, when thin, minimize the diffusion
distance necessary for the analyte to traverse during extraction and
Different sensing mechanisms are employed in various reported sensor
devices. For example, Sadeghi3 developed a
potentiometric sensor based on a polymer imprinted for the antibiotic
levamisole hydrochloride, which was embedded in a polyvinylchloride
membrane. The sensor, with a sensitivity in the µM range, a
response time of less than 15s and a lifespan of four months, was
highly selective to the antibiotic in either pure or tablet
formulation. We have reported on a capacitive sensor targeted to
solutions of amino acids and hosted in a Nylon-6 film, a true
parallel-plate capacitive structure.4
Operated in an
AC mode, these sensors exhibited significant shifts in the dissipation
factor peaks, providing information on whether the target analyte
was present in the sensor or had been removed. Moreover, the
sensors built for a specific amino acid were insensitive to the
adsorption of other, competing amino acids.
More recently, we have focused on chemiresistive sensors. The
imprinted polymer solution is spin- or dip-coated onto a silicon chip
upon which a set of interdigitated electrodes were lithographically
produced. The polymer films are kept very thin, 100-300nm, so that the
adsorption event is detected and reported via the change in the
conductivity of the device. An important application of this technology
is the development of a sensing film to detect the presence of
secondhand cigarette smoke by specifically adsorbing nicotine in the
ambient air.5 This device relies on a
polymer film, polyaniline, as the reporting agent. A typical
response to the presence of secondhand smoke from a single cigarette is
shown in Figure 3. The increase in resistance is immediate and the
decease from the maximum occurs as the cigarette is extinguished.
Incorporation of such a film in a personal sensor will provide the
means to notify those most sensitive to the components of smoldering
tobacco that they must take precautions.
Figure 3. The response of a
polyaniline-based sensor to secondhand cigarette smoke via the
detection of nicotine.
A similar device, employing a different adsorbent layer, but also
using polyaniline as the reporting element, has been developed to
specifically detect the presence of gaseous formaldehyde at sub-ppm
levels.6 Again providing a means to ensure
the safety of
those who might be adversely impacted by exposure.
Both of the resistance-based sensors described above rely on
polyaniline as the conductive element. This is a restrictive situation,
since the change in conductivity requires that the analyte abstract a
proton from the doped polymer. We have developed a more general
approach in which the conductive element is single walled carbon
nanotubes.7 Typically, a fraction of carbon
metallic properties and these tubes serve as the reporting agent for
adsorption. The MIP is coated onto the nanotubes, which are then
deposited across the electrodes. This is a general technique, and
while we expect to find numerous uses for the technology, one specific
application we have reported is testing for the presence of cotinine in
urine. Cotinine is the major metabolite of nicotine and a more
sensitive test is required in order to assess exposure to secondhand
cigarette smoke in individuals.
- J.J. BelBruno, “Molecularly Imprinted Polymers:
receptors with wide-ranging applications”, Micro and Nanosystems, 1,
- S.E. Campbell, M. Collins, L. Xie and J.J.
morphology of spin- coated molecularly imprinted polymer films”,
Surface and Interface Analysis 41, 347 (2009).
- S. Sadeghi, F. Fathi and J. Abbasifar,
“Potentiometric sensing of
levamisole hydrochloride based on molecularly imprinted polymer”,
Sensors and Actuators B 122, 158 (2007).
- J.J. BelBruno, G. Zhang and U.J. Gibson,
“Capacitive sensing of
amino acids in molecularly imprinted nylon films”, Sensors and
Actuators B 155, 915 (2011).
- Y. Liu, A. Antwi-Boampong, S.E. Tanski, M. Crane
BelBruno, “Detection of secondhand cigarette smoke via nicotine using
conductive polymer films”, Science (submitted, Sept. 2012).
- S. Antwi-Boampong and J.J. BelBruno, “Detection
vapor using conductive polymer films”, Sensors and Actuators B,
(submitted, Aug. 2012).
- S.W.R. Dunbar and J.J. BelBruno, “Molecularly
polymer-carbon nanotube sensor targeted to cotinine”, Chemical Sensors,
in press (2012).