Philippe Buhlmann
RESEARCH OVERVIEW
The common theme of the research activities in the Buhlmann group is the application of
molecular recognition and, in particular, the use of synthetic receptors for chemical sensing in complex
real-life environments. One goal of our research is the development of chemical sensors that put receptors
to their most effective use, permitting the selectivities and detection limits required for real applications,
and providing maximum input for the rational development of new receptors. A second goal is the
development of new strategies that permit the use of robust chemical sensors that excel not only in the
laboratory but withstand the harsh conditions of long term monitoring, e.g., in the environment, in
industrial process control, or upon implantation into the human body. Thereby, our research contributes to
achieve societal goals as improved healthcare, food safety, manufacturing processes, and public safety.
In pursuit of these goals, our research group has been pushing the limits of fluorous chemistry,
explored new applications of carbon nanomaterials, developed plasticized perfluoropolymer membranes,
and demonstrated the application of novel receptors that provide for unprecedented selectivities, detection
limits, and long term signal stability. While pursuing a particular goal, we like to learn as much as
possible about the fundamental properties of the novel materials we use and the inherent capabilities of
sensing modes we explore because we believe that this maximizes the impact of our research. For
example, while developing receptors for the detection of explosives, we discovered a lack of efficient
methods to interpret the Job’s plots that are so often used to determine the stoichiometry of host–guest
complexes. The method that we developed in response is very general and applicable in numerous fields
of chemistry, to the extent that we believe that the publication in which we described this method [90]
ought to become a citation classic of host–guest chemistry. Similarly, our desire to thoroughly understand
the serendipitous observation of an unusual response function of a fluorous membrane ion-selective
electrode (ISE) led us to explore the effect of the simultaneous formation of multiple complexes of the
target ion in the ionophore-doped sensor membrane [93], closing a gap in ISE theory. This type of proper
understanding facilitates the development of new sensors with a scope well beyond the fluorophilic crown
ether ionophore we set out to explore in first place. These are just two of the most recent examples
illustrating our approach. The following describes the accomplishment of our research group in several
areas, focusing on the years 2006 to 2012 but mentioning earlier work to put more recent
accomplishments in a context.
Receptor-Doped Potentiometric Sensors
While the Buhlmann group has also been working in the field of scanning tunneling microscopy
and different methods of electroanalysis (see below), the development of potentiometric receptor-doped
ISEs for new applications enabled by higher selectivities, lower detection limits, and longer lifetime has
been a core interest of the group. Before discussing of contributions of the Buhlmann group to this field,
it is appropriate to briefly describe what receptor-doped ISEs are [45,46,48,58,92].
The key component of a receptor-based ISE is the lipophilic receptor that is capable of selectively and
reversibly binding analyte ions. It is usually called ionophore or ion carrier. For routine measurements,
these ionophores are incorporated into a polymeric membrane, which is typically placed between the
sample and an inner filling solution contacting an internal reference electrode. The membrane is a
water-immiscible phase in which the ionophore and ionophore complexes may move by diffusion, which
allows for equilibration of ion transfer at the phase boundary between the ion-selective sensing membrane
and the sample. This establishes an analyte-dependent phase boundary potential and, thereby, the
potentiometric response of the electrode to the activity of the target ion (see Fig. 1). The electrode
selectivity is related to the equilibrium constants that characterize the exchange reaction of target and
interfering ions between the organic and aqueous phases. It depends on the ratio of complex formation
constants of these ions with the ionophore in the membrane phase, and the free energies of ion transfer
from the sample into the membrane phase. For example, an electrode will respond with a particularly high
selectivity to a desired (primary) anion if the free energy for the transfer of this anion from the sample into
the membrane is smaller than for another (interfering) anion, and if the ionophore binds the primary anion
17
log corg
-4
Cl-6
K+
-8
2
-10
-6
Philippe Buhlmann
-4
-2
0
2
log aKClaq
Phase boundary potential / mV
B
more strongly than the interfering anion.
Besides the ionophore, the membrane contains commonly a
lipophilic ion that is used to control the stoichiometry of the
analyte–ionophore complexes [7,8,35]. For example, due to the
requirement for electroneutrality in the membrane bulk, the use of
log a
an electrically neutral dianion-selective ionophore and a highly
+
lipophilic monocation, R , in the theoretically optimized ratio of C
100:162 results in a ionophore-to-dianion ratio in the bulk of the
membrane of 100:81 (see Fig. 2). For this ratio, all dianions may
R
Organic phase
K
bind to an ionophore, and there is an excess of ionophore. On the
R
K
K
(bulk)
K
R
other hand, exposure of the same membrane to a dianion-free
R
Charge separation
layer (nm dimension)
solution of a monoanion results—after interfacial ion transfer—in
Cl
Cl K
K Cl
K
Cl
K
K
Aqueous phase
Cl
an ionophore-to-monoanion ratio in the bulk of the sensing
Cl K
(bulk)
Cl K
membrane of 100:162. Unless one ionophore molecule can bind
more than one anion, a significant fraction of the monoanions in
the membrane remain non-complexed, and the potentiometric
Fig. 1: The phase boundary potential at the
response to the monoanion is poor. The highly lipophilic ions liquid–liquid interface of sample and
that make this possible are said to provide for ionic sites. They sensing membrane is the oritin of the
familiar Nernstian response of the ISE.
do not leave the membrane due to their very high lipophilicity.
100
50
0
59.2 mV
-50
-6
-4
-2
0
2
KClaq
+
-
+
-
-
K+
Cl-
-
+
-
-
K+
Cl-
K+
Cl-
+
-
-
+
+
+
+
-
-
+
-
+
+
From ref. 92.
Aqueous
phase
Sample
contains
only
primary
analyte X2-
X2–
Membrane
phase
K
2–
X
X2–
X
2–
X
2–
X
2–
+
R+
R
+
R+
R+
R+
R
X2–
X2– X2–
+
R
+
R
X2–
+
X2–
+
X2–
+
+
Y–
Y–
+
+
–
R
–
R
analyte
X2-
-2
log [L+ (mol/kg)]
-3
-4
Yinterfering ion
-5
-6
-150
-100
-50
0
50
100
-zR[RzR ]/Ltot (mol %)
Sample
contains
only
interfering
ion Y–
Y–
Y– Y– K
Y– Y–
Y– Y–
Y
–
Y–
Y
–
Y
–
R+
R+
R+
R+
R+
R+
Y–
Y– Y–
Y
–
Y–
Y
–
Y
–
R+
R+
Y–
R–
R–
Highest Selectivity
Fig. 2: Dependence of the free ionophore concentration—and consequently selectivity— on the charge
sign and concentration of ionic sites. Top row and blue
line: divalent target ion. Bottom row and red line:
monovalent interfering ion. From ref. 92.
The application of receptor-based ISEs has
evolved into a well established routine analytical
technique. It can be estimated that yearly over a
billion ISE measurements are performed in clinical
laboratories in the US alone [46]. ISEs are used
nowadays also in many other fields, such as
physiology, process control, food industry, and
environmental analysis. Undoubtedly, receptorbased sensors are one of the most important groups
of chemical sensors in real life analysis. Continuing
challenges for ISE research include the development
of receptors for analytes for which selective ISEs
are not available yet, the development of strategies
to lower detection limits, and the development of
ISEs with long term stability.
Biofouling of Receptor-Based Polymeric Sensing Membranes
A project that I started in Tokyo as principal investigator and finalized at Minnesota [39] got me
particularly interested in biofouling of chemical sensors. The initial goal of that research was the
development of a sensor for creatinine, one of the most commonly measured species in the clinical
laboratory. To our surprise, the selectivity of our optimized receptor-free potentiometric sensor exceeded
the selectivities of previously published creatinine sensors based on synthetic receptors. Clearly, those
sensors are examples for the inefficient use of receptors. However, we tested our receptor-free sensor in
urine samples, only to find that urine caused major drifts and longterm losses in selectivity. Using various
techniques of spectroscopy, mass spectrometry, chromatography, and potentiometry, we established that
the cause of the drifts was not related to ionic interferents or the adsorption of proteins onto the surface of
the sensor membranes. Instead, we showed that naturally occurring, electrically neutral compounds such
as lipid, cholesterol and porphyrin derivatives entered our hydrophobic polymeric sensing membranes,
causing selectivity losses by offering interaction points for interfering species that were well discriminated
18
Philippe Buhlmann
by uncontaminated membranes. Subsequently, we were able to generalize this finding by the observation
of the same effect of urine components on ionophore-based sensors. In particular, the selectivity for K+
over Na+ of the valinomycin-based ISE worsened by a factor of six [39], which is a finding of substantial
importance as this potassium ion selective sensor is used in the USA alone to measure approximately 80
million samples per year.
We observed a similar case of biofouling when, in collaboration with the Metzger group from the
Department of Food Science and Nutrition (University of Minnesota), we tested receptor-doped
polymeric membrane sensors in cheese [57] as an approach to study the complex chemical equilibria
involved in cheese ripening [64]. No literature precedent for direct measurements with receptor-based
sensors in cheese existed, and the high protein and lipid content of cheese suggested that biofouling might
be severe. To our surprise, the high selectivity of our receptor- based H+-selective solvent polymeric
sensors enabled accurate measurements in undiluted homogenized process cheese. However, the analysis
of selectivities before and after cheese exposure confirmed selectivity losses. For example, the selectivity
for H+ over K+ worsened upon cheese exposure for 48 h by more than three orders of magnitude.
Consistent with our earlier conclusions, the exposure of the H+ receptor-based sensors to the principle
cheese protein rennet casein caused no selectivity losses, while exposure to hydrophobic cheese
components (lipids and hydrophobic peptides) resulted in substantial selectivity losses.
In conclusion, our studies with urine [37] and cheese [59] matrices showed that the extraction of
electrically neutral hydrophobic sample components affects the selectivities of polymeric membrane
sensors. This represents an important step in the understanding of biofouling of polymeric membrane
sensors, which for many years was erroneously attributed exclusively to adsorption of sample components
onto sensor surfaces. We believe that it is important to realize that there is for any type of chemical sensor
not one unique type of biofouling, but that for each type of sensor and application biofouling is a
combination of several phenomena that limit the sensor lifetime and performance. Importantly, the
identification of a new type of mechanism for biofouling suggests new approaches to reduce biofouling.
For example, grafting of hydrophilic groups to surfaces is well documented to reduce biofouling, and NO
releasing materials drastically reduce platelet adhesion to polymeric sensing membranes in blood vessels.
However, neither strategy is suitable to prevent the selectivity losses by the mechanism we have
discovered. The following section describes our approach to prevent the problem of lipid extraction into
receptor-doped polymeric sensor membranes using fluorous sensing membranes and the amazing
increases in ion selectivities that we observed with those unique sensing matrixes.
Fluorous Phases as a New Approach to Reduce Biofouling and Increase the Selectivity of ReceptorBased Chemical Sensors
Most chemists are taught that polar solvents such as water are
miscible with other polar solvents but immiscible with nonpolar
solvents such as alkanes. It is less well known that many
perfluorocarbons are not miscible with hydrocarbons precisely
because hydrocarbons are too ”polar”. Indeed, alkanes are much
more polarizable than perfluorocarbons. On the π* scale of solvent
dipolarity/polarizability, water has a π* value of 1.09, cyclohexane
defines 0, and perfluorooctane has the surprisingly low value of
–0.41. To emphasize the peculiar character of such perfluorinated phases, they have been called
“fluorous”. Fluorous matrixes have great promise to reduce biofouling not only because they are
chemically very inert and were shown to promote cell growth on their surfaces to a much lesser extent than
most polymers presently used for receptor-based sensors, but also because they dissolve lipophilic
interferents poorly. For example, at 37 ºC stearic acid has a solubility in hexane of 430 mM, which is
twenty times higher than the typical receptor concentration in a polymeric sensing membrane. In sensor
membranes, such high concentrations cause major selectivity losses. In contrast, the solubility of stearic
acid in the fluorinated solvent trans-1,2-bis(perfluorohexyl)ethylene is only 0.026 mM, which is three
orders of magnitude lower than the typical receptor concentration. The Buhlmann group started a program
to exploit the unique properties of fluorous phases for chemical sensing with receptor-based membranes.
19
Philippe Buhlmann
Importantly, these extremely nonpolar perfluorinated matrixes are very different from only partially
fluorinated polymers with high densities of polar functional groups, such as the frequently used ion
exchanger Nafion. The latter are highly polar, very hydrophilic, and soak up large amounts of water.
Arguably, these partially fluorinated ion-exchange polymers are on the opposite end of the polarity scale
from fluorous phases.
A key hurdle we overcame in the development of fluorous sensing membranes was the
fabrication of fluorous, receptor-doped membranes doped with fluorophilic salts in different
stoichiometric ratios to the receptor [60,63,75,85]. This task was not trivial since no salts with solubility in
perfluorocarbons were reported in the literature prior to our work. We showed that highly hydrophobic
salts commonly used in the field of receptor-doped chemical sensing membranes, such as
tetraphenylborate and tetralkylammonium derivatives, are insufficiently soluble in fluorous phases.
Subsequently, we reported the first synthesis of pure potassium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate and showed it to be suitable in perfluorocarbons [60]. In view of the extreme nonpolarity of
fluorous solvents, it is not surprising that we found that ion pair formation constants of this anion with
various cations in fluorous phases significantly exceed previously reported values for any other solvent
and ion pair [60,63].
Interestingly, the potentiometric selectivities of our fluorous cation-exchanger membranes span a
remarkably wide range of more than 16 orders of magnitude [60], while the selectivity range for
membranes prepared from conventional ion exchanger membranes is limited to only 8 orders of
magnitude. Since the high selectivities of the
fluorous ISE membranes are the result of the
low extent of solvation of interfering ions in
the fluorous phase, this eventually was a key
reason for the improvement of the
selectivities of receptor-doped fluorous
membrane sensors and the lowering of
detection limits into the ppt range (see
below).
Our initial studies with fluorous sensing membranes were performed with a tricyclic fluorocarbon
as the fluorous matrix. The absence of specific ion solvation explained the extraordinarily high
potentiometric selectivities. However, many popular perfluorinated solvents and perfluoropolymers
contain heteroatoms, such as the nitrogens in perfluorotrialkylamines and the oxygens in
perfluoropolyethers. Prior to our work, the literature contained hardly any (and then only qualitative)
evidence about the coordinating properties of heteroatoms in perfluorocarbons. Hence, understanding the
coordination properties of heteroatoms in perfluorocarbons was not only essential to the development of
chemical sensors, but is also of substantial fundamental interest. We showed that perfluorotripentylamine
has a pKa below –0.5 and that a
perfluorotetraether binds to Li+ and Na+ with
the extremely small binding constants of 2.0
and 2.6 M-1, respectively [63]. This can be
explained by the high electronegativity of the
fluorine substituents, which drastically
reduce the Lewis basicity of the ether and
amino groups in these compounds, and is
consistent with the nearly planar structure of
perfluorotrialkylamines.
More recently, we also reported on the cation-coordinating properties of perfluoro-15-crown-5
[80]. Our interest in this compound arose from the fact that it was shown in the literature to bind the
anions O2– • and F– in the gas phase, an observation rather unusual for macrocyclic crown ethers, which
have become famous as cation binding hosts through the work of Nobel prize winners Pederson and
Cram. Perfluoro-15-crown-5 is used to image the distribution of molecular oxygen in the living body
20
Philippe Buhlmann
using magnetic resonance imaging (MRI) due to the sensitivity of the relaxation time T1 of the 19F nucleus
to molecular oxygen. In the first quantitative study of cation binding to a perfluoro crown ether, we
confirmed that although cation binding to perfluoro-15-crown-5 is very weak, it is measurable by
potentiometry [80].
Development of Flourous Polymeric Membranes
Having closed a gap in the quantitative knowledge of cation binding to perfluoroethers and
having confirmed that cation binding to such compounds is very weak [63,80] opened the way to the use
of oxygen containing perfluoropolymers as fluorous membrane matrixes with superior mechanical
stability. Our first sensor results were obtained with inert porous Teflon support impregnated with
fluorous liquids [60]. This system is ideal for fundamental studies since it can be used with any fluorous
liquid, permitting the evaluation of fluorous compounds with a wide range of structures and functional
groups. However, for use the use of fluorous membrane sensors in “real life” applications, we had to
develop a new type of fluorous polymeric membranes. On one hand, perfluoropolymers such as Teflon
are at least partially crystalline in nature and are not suitable as matrixes for sensing membranes because
they do not dissolve receptors. Even if they would, the electrical resistance of such membranes would be
too high for practical purposes. On the other hand, conventional perfluoroelastomers contain cross-linking
units with metal coordinating properties that would diminish the sensor selectivity. Therefore, we chose
to focus initially on amorphous perfluoropolymers plasticized with inert fluorous low-molecular-weight
plasticizers. We found that plasticization lowers the glass transition temperatures of the perfluoropolyether polymers Cytop and Teflon AF2400 below room temperature, in the latter case as low as –128
ºC [71,79]. This was an important step towards our goal of developing fluorous membrane
electrochemical. However, we believe that the availability of plasticized perfluoropolymers with low
glass transition temperatures will also be useful for many other applications, including the fabrication of
optical devices and the protection of miniaturized devices from chemically aggressive media. From a
materials science point of view, the low and nonspecific cohesion forces in perfluorinated compounds
suggest that some of our blends are also rather ideal examples for the Lodge-McLeish model of
homogenous polymer blends with two glass transition temperatures [71].
The development of these fluorous plasticized polymeric membranes in our group was followed
by their use in potentiometric sensors [79]. Electrodes for pH measurements with membranes composed
of Teflon AF (i.e., poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole]-co-poly(tetrafluoroethylene))
as polymer matrix, a linear perfluorooligoether as plasticizer, tetrakis(3,5-bis(perfluorohexyl)phenyl)borate to provide ionic sites, and one of several fluorophilic trialkylamines as H+-ionophore were
investigated. All electrodes had excellent potentiometric selectivities and showed theoretical (Nernstian)
responses to H+ over a wide pH range. We were initially puzzled to find that for membranes of low
ionophore concentration, the polymer affected the sensor selectivity noticeably at polymer concentrations
larger than 15%. Also, the membrane resistance increased quite strongly at high polymer concentrations,
which cannot be explained by the Mackie–Meares obstruction model. We were able to explain these
observations with the development of a multiparameter simplex algorithm that fitted simultaneously the
dependence of the electrical resistance and multiple selectivities on the polymer content of these ISE
membranes. It showed that the ISE selectivities and resistances depended on the polymer concentration
because of COOH groups in Teflon AF2400 with a concentration of one functional group per 854
monomer units of the polymer. In these fluorous membranes, the COOH group was found to binds to Na+,
K+, Ca2+, and the unprotonated ionophore with binding
constants of 103.5, 101.8, 106.8 and 104.4 M–1, respectively.
Subsequently, spectroscopic evidence showed that the
COOH groups formed by the hydrolysis of carboxylic
acid fluoride (-COF) groups originally present in Teflon
AF2400, and upon understand this effect, potentiometry
showed that the use of higher ionophore concentrations
was able to remove the undesirable effect of these COOH groups almost completely. These results were
21
Philippe Buhlmann
unique as they represented the first demonstration of fluorous polymeric ISE membranes, the first report
of cation binding to Teflon AF, and the first discussion of the conductivity of ion-doped fluorous
membranes. Moreover, its was the first time that Teflon AF was experimentally shown to contain C(=O)F
groups, despite the fact that more than 1100 publications had been reported to that point on the use of
Teflon AF (recently approximately 100 per year).
Development of Highly Fluorophilic Ions And Their Use for Trace Level Environmental Studies
As pointed out above, our needs for fluorophilic anions suitable for chemical sensor work were
satisfied with fluorophilic tetraphenylborate derivatives [60,63]. The search for appropriate fluorophilic
cations proved to be much more difficult [75,85,91]. Initially, a fluorophilic methyltriarylphosphonium
cation was synthesized and an inert liquid fluorous matrix was doped with a salt of this cation [75]. The
detection of the environmental contaminants perfluorooctanoate (PFO–) and perfluorooctylsulfonate
(PFOS–) with electrodes with such membranes with very high selectivity was the first demonstration of
the potentiometric detection of these analytes. While the selectvities for PFO– and PFOS– over chloride
pot
pot
were very high—more than 7 and 10 orders of magnitude, respectively ( log K Cl , PFO = 7.4, log K Cl , PFOS =
−
−
−
−
10.6)—we observed the decomposition of the fluorophilic cation ion to a phosphine oxide in the presence
of hydroxide. This caused the sensor responses to be slow and resulted in drifts, even when the hydroxide
ion was formed only in very small quantities in the presence of water and interfering anions that acted as
weak bases. Exploring alternatives, we worked first with a fluorophilic tetraaklkylphosphonium cation
(i.e., Rf8(CH2)2)(Rf6(CH2)2)3P+I–) and then a fluorophilic ion with the bis(phosphoranylidene)ammonium
group (P=N+=P) [85,91]. The latter was the first fluorophilic cation of its kind and provided a far more
favorable selectivity over hydroxide. Since the fluorophilic P=N+=P cation is the most chemically stable
and coordinatively inert fluorophilic cation that we have tested to date, we believe that this new
compound will be useful not only to the further development of ISEs but also to those with an interest in
phase transfer catalysis and other applications of fluorous chemistry.
Using these fluorophilic cations, we further optimized the
ISEs for PFO– and PFOS– and demonstrated detection limits as
low as 0.07 ppb. These values are comparable with results
obtained using established techniques such as GC–MS, LC–MS,
and LC–MS–MS, but the measurement of PFO– and PFOS– with
ISEs avoids lengthy sample preconcentration, can be performed
in-situ, and is much less costly. Even when eventual
spectrometric confirmation of analyte identity by MS is required,
in-situ monitoring with ISEs or prescreening of large numbers of samples may be of substantial benefit.
To demonstrate a first real life application of these electrodes, in-situ measurements were carried out to
investigate the adsorption of PFOS– onto Ottawa sand, which is a standard sample often used in
environmental sciences [95]. The results obtained are consistent with those from an earlier LC–MS study,
validating the usefulness of these sensors for environmental studies. Ongoing work in the Buhlmann
group is testing the use of these ISEs for analysis in samples provided by a collaborator from the US EPA
(Environmental Protection Agency).
Potentiometric Sensors with 3DOM Carbon Solid Contacts
Because of the interest in the mass fabrication of ISEs and in order to measure in small volumes
such as single cells, the miniaturization of these devices is of particular interest. This is hindered by the
inner filling solution, which is in contact with the inner reference electrode and is part of every
conventional ISE. Inner filling solutions readily dry out and are the cause of osmotic pressure that easily
ruptures miniaturized sensing membranes. This motivated several research groups to develop different
types of solid contact ion-selective electrodes (SC-ISEs). Initially, ionophore-doped membranes were
simply applied to a metal wire. On a short term basis, such devices work surprisingly well. However,
extended use results in drift of the measured potentiometric signal, as expected because of the lack of a
22
Philippe Buhlmann
redox couple defining the phase boundary potential. This is often followed by catastrophic failure due to
formation of a water film between the sensing membrane and the metal, resulting in delamination of the
sensing membrane. As a result, various different materials have been used to interface the sensing
membranes with the underlying metallic leads. From 1992 until a few years ago, the most promising type
of materials appeared to be redox-active conducting polymers such as polypyrrole and polythiophene
derivatives. Painstaking work in leading laboratories has improved these types of devices, but it is widely
accepted that their performance is still not fully satisfactory. Particular problems are the limited
electrode-to-electrode reproducibility of the y intercept of calibration curve, and drifts of this intercept
caused by the slow uptake of water and oxygen into the conducting polymer layer.
To this end, we introduced three-dimensionally ordered
macroporous (3DOM) carbon as a novel material for SC-ISEs
[67,78,81,87]. For this purpose, we collaborate with Andreas Stein
(University of Minnesota), whose inorganic chemistry group has been
supplying us with 3DOM carbon materials. 3DOM carbon is a
nanostructured material based on a highly porous skeleton of glassy
carbon. The uniqueness of this material arises from the fact that the
pores are not only almost perfectly spherical and have identical size, but
they are also arranged in highly regular periodic arrays and are Fig. 3 Scanning electron microsinterconnected in three dimensions. These structures are prepared with copy image of 3DOM carbon
colloidal crystal templating through infiltration of a close-packed array infused with ionophore-doped
of monodisperse polymer spheres by a precursor that is subsequently polymeric sensing phase.
cured at high temperature to form a solid glassy carbon skeleton. The
pores that are on the order of a few hundred nanometers in diameter are obtained by burning out the
polymeric template spheres. The 3DOM carbon monoliths prepared this way have a well-connected wall
structure that is electronically conducting.
When the 3DOM pores are filled with a polymeric phase doped with ionophore and ionic sites,
the well-interconnected pore and wall structure of 3DOM carbon results in a nanostructured material that
exhibits high ionic and electric conductivity. ISEs with 3DOM carbon as the solid contact replacing the
inner filling solution exhibited theoretical (Nernstian) responses and an excellent resistance to
interference from oxygen and light [67,78,81,87,95]. With a view to long-term measurements without
recalibration, the long term drifts of as low as 11.7±1.0 uV/h over 70 h are particularly promising, a
performance that exceeded any prior work. This excellent long-term stability is explained by the large
interfacial area, which results in a very high capacitance, as confirmed by cyclic voltammetry, chronopotentiometry, and electrochemical impedance spectroscopy. Control experiments with untemplated
carbon solid contacts shows that the pore structure is indeed an essential feature for the excellent
electrode performance. The functional groups on the 3DOM carbon cannot be ignored, though, as it
causes the formation of a water layer at the interface of the 3DOM carbon and the ionophore-doped
polymeric membrane.
Our first publication on 3DOM carbon solid contact electrodes [67] was followed by papers from
several other research groups that followed up on our idea and also explored nanostructured carbon
materials forming high capacitance interfaces, among others carbon nanotubes. Five years after its
publication in Analytical Chemistry, our first paper on this topic is among the 10% most cited articles
published in the same year and journal. More importantly, the use of 3DOM carbon solid contact
electrodes permitted us not only to obtain unprecedented long term stabilities, but it has been besides the
use of fluorous phases the second most important factor permitting us to detect analytes in the ppt range
(see above for perfluoroalkyl anions, and below for Ag+).
We have also shown 3DOM carbon to be very useful as solid contacts for reference electrodes
based on ionic liquids [96]. The unique promise of this new type of reference electrodes is that they may
replace conventional salt bridges. The latter are easily contaminated, their junctions readily clog up in
biological samples, they are difficult to miniaturize, and in long term use they contaminate samples. In the
case of the ionic liquid electrodes introduced by Kakiuchi and co-workers, the reference electrode
23
Philippe Buhlmann
contacts the sample with a polymeric film doped with the ionic liquid. Continuous leaching of a very
small amount of ionic liquid into the sample determines the phase boundary potential at the interface of
the immiscible sample and reference membrane, which differs substantially from the liquid junction
potential at the interface of the miscible sample and salt bridge. The use of a relatively hydrophobic ionic
liquid ensures that the selectivity of the reference membrane for this ionic liquid is high and that the
amount of ionic liquid distributing into the sample is small at any given time, improving the lifetime of
this reference electrode.
Our own attempt to combine ionic liquid-based reference electrodes with 3DOM carbon solid
contacts and use them in real life samples led to (initially) puzzling results that took us quite a while to
understand with a quantitative phase boundary model that considers all relevant ionic distribution
equilibria and ion fluxes. Eventually, this led to three findings that considerably advance the
understanding of ionic liquid-based reference electrodes [96]. We showed for the first time that
protonation of the very popular ionic liquid anion bis(trifluoromethyl)sulfonimide in the hydrophobic
membrane phase drives co-extraction of H+ and the ionic liquid anion from the sample into the reference
membrane. Similar effects are likely with other ionic liquids too, and need proper attention for the
reference electrode design. We also made the first observation of transmembrane ion fluxes in
membrane-based reference electrode half cells. Finally, we showed how these transmembrane ion fluxes
can be avoided using 3DOM carbon solid contacts, which made it possible for the first time to use these
novel ionic-liquid based reference electrodes for measurements in complex real samples (milk).
Unprecedented Selectivities with Receptor-Doped Membranes
Because of their extremely low polarity and polarizability, fluorous media solvate potentially
interfering ions poorly, resulting in a much improved discrimination of such ions. However, doping of
fluorous sensing membranes with receptors is required to prepare fluorous sensing membranes with
selectivities for specific analytes. The insolubility of conventional receptors in fluorous solvents
substantially complicates this effort. While we synthesize fluorophilic compounds if necessary, we are
lucky that we were also able to attract the interest of organic chemists who use fluorous chemistry for
synthetic and catalytic purposes. In particular, Drs. Jozsef Rabai (Eötvös Loránd University, Budapest,
Hungary), Gianluca Pozzi (CNR, Milano, Italy), and John Gladysz (Texas A&M University, College
Station) provided us with some fluorophilic receptors. The following describes several particularly
successful attempts to develop receptor-doped fluorous membrane ISE.
Fluorous membrane pH electrodes were prepared with several fluorophilic H+-selective
ionophores [73]. These ionophores are trialkylamines with three electron withdrawing perfluoroalkyl
groups separated from the central nitrogen by (CH2)n spacers of varying lengths, with n varying between 1
and 5. Their pKa values in the fluorous matrix were quantitatively determined, and were found to be as
high as 15.4 ± 0.3; the corresponding electrodes exhibited selectivities for H+ over K+ as high as 1>10–12.8,
with more accurate selectivity coefficient impossible to determine directly because of lack of interference.
The pKa and selectivity were found to follow the trends expected from the degree of shielding by the
(CH2)n spacers of the ionophores. The selectivities of the ISE with [CF3(CF2)7(CH2)5]3N as ionophore
were not only greater than those of analogous sensors with non-fluorous membranes but were of the same
magnitude as the best ionophore-based pH sensors ever reported. Subsequent stability tests in view of
industrial applications confirmed that the electrodes worked still after 2.5 h exposure to 3% NaOH at 90
ºC.
While developing these fluorous membrane H+-selective ISEs,
H
H7C3
we observed that the potentiometric response to the
H
R
H
tetrabutylammonium cation depended on the H+ ionophore. Motivated
H
N R
by the desire to understand this unexpected result, we further H9C4 N
H7C3
investigated this effect by conductimetry using a cell custom built for
H
R
H7C3
samples with particularly low conductivity. All observations are
H
consistent with the formation of N···C–H–N+ type hydrogen bonds
between the nitrogen of the ionophore and hydrogen atoms in alpha position to the positively charged
24
Philippe Buhlmann
quaternary nitrogen of NBu4+. Similar interactions were observed in crystals with techniques such as
infrared spectroscopy and x-ray and neutron diffraction, but observations of N+–C–H···N type hydrogen
bonds in liquid phases have not been reported so far. Conductimetry also confirmed that in this fluorous
system ion pairs, triple ions, and higher ionic aggregates dominate over single ions, and the ionophore
increases the conductivity by favoring the formation of ionic aggregates through N+–C–H···N type
hydrogen bonds. These findings emphasize once more the unique chemistry of fluorous phases, resulting
from their exceptionally low polarity.
Using fluorophilic Ag+ ionohores, we combined for the first time fluorous sensing phases with
three-dimensionally ordered macroporous (3DOM) carbon as solid contacts for ISEs [87]. The fluorous
nature of the sensing phase and a very efficient ionophore resulted—in comparison to the best
conventional ISE reported to date—in an increase in selectivity of two to three orders of magnitude over
many interfering ions. Among the impressive selectivity for Ag+ are, among others, selectivities of
1:10–11.6, 1:10–10.2, 1:10–13.0, and 10–13.2 for K+, Pb2+, Cu2+, and Cd2+, respectively. Moreover, a 4.1 ppt
detection limit made possible by the 3DOM carbon solid contact, which is the lowest detection limit
reported for an Ag+ ISE to this date. In an ongoing collaboration with the group of Christy Haynes
(University of Minnesota), we are assessing ion dissolution from silver nanoparticles to better understand
the toxicity of these nanoparticles to the bacterium Shewanella oneidensis. A key advantage of using for
this purpose an ISE rather than alternative analysis methods such as atomic spectroscopy is that
measurements can be performed in real time and in situ, without any sample preparation. Moreover, the
ISE can readily distinguish between free Ag+ and Ag+ bound to proteins and other cell components.
Indeed, the clinical relevance of activities of free ions is one of the reasons that led to the complete
replacement of atomic spectroscopy by receptor-based sensors in clinical chemistry [46].
Increases in selectivity by several orders of magnitude were
also obtained by use of manganese(III) complexes of three fluorophilic
salen derivatives to prepare CO32- ISEs. The fluorous membrane ISEs
exhibited selectivities for CO32- that exceed those of previously
reported ISEs. Most important in view of clinical applications, the
interference from chloride and salicylate was reduced by two and six
orders of magnitude, respectively. Performing this work using
state-of-the-art ISE theory, we were able to not only fully optimize the
sensor performance but also report quantitatively the stoichiometries
and stabilities of the ionophore complexes, providing all the
information a host–guest or organometallic chemist could wish for. The optimum CO32- selectivities were
found for sensing membranes composed of anionic sites and ionophore in a 1:4 molar ratio, which results
in the formation of 2:1 complexes with CO32- with stability constants up to 4.1 × 1015. The exceptional
selectivity of fluorous membranes doped with these carbonate ionophores suggests their use not only for
potentiometric sensing in clinical, biological, and environmental samples but also for other types of
systems in which selective carbonate binding is required. Ongoing work in the Buhlmann group is testing
the use of these sensors in biological samples.
In another ongoing project, we are trying to expand the use of receptor-doped membrane ISEs to
cyanide sensing. Surprisingly little work has been performed in the past to develop sensors for this
analyte, despite its use in numerous industrial applications (polymer synthesis, electroplating, metallurgy,
mining). Interest in cyanide also arises due the widespread of plastics and the increasing number of cases
of HCN poisoning as a result of residential fires. In France, victims of smoke inhalation are now given
HCN antidotes routinely before they reach the hospital, in the US cyanide antidotes have been introduced
recently for on-site use, and fire fighters are asking for improved on-site HCN analysis. We doped ISE
membranes with Co(II), Co(III) Zn(II), Ni(II), Cu(II) and Fe(III) metalloporphyrins, and found them all to
function as electrically neutral ionophores for CN–. While both the Co(III) and Fe(III) porphyrins with
their positive charges on the metal center seemed likely to bind up to two axial CN– ligands, only the
Co(III) porphyrin was found to strongly bind a second CN– ligand. The electrode membranes doped with
Zn(II) tetraphenylporphyrin provided the highest selectivity and were optimized by adjusting the
25
Philippe Buhlmann
site-to-ionophore ratio to achieve the highest CN– selectivity. The Zn(II) tetraphenylporphyrin-based
CN–-selective electrodes exhibited the best discrimination of OH–; no pH effect was observed even at pH
11, which eliminates a key problem encountered in earlier attempts to prepare ISEs for the analyte. Our
CN– ISE fulfills US regulatory requirements for drinking water, and it gives a basis for the development
of analogous gas sensors [98].
In the late 1990s, Buhlmann and co-workers reported the first host compounds with two thiourea
groups that bind inorganic phosphate by multiple hydrogen bonding [9,10,14,19], providing well cited
examples of synthetic hydrogen bond forming hosts for inorganic anions. The contribution “Strong
hydrogen bond-mediated complexation of H2PO4– by neutral bis-thiourea hosts” by Buhlmann et al. [14],
e.g., was by 2012 the 10th-most cited of 1421 articles published in Tetrahedron in 1997. Therefore, we
recently investigated a number of new bis-thiourea spacers with different geometries to better understand
how spacers linking the thiourea groups affect the host affinity
and selectivity. Interestingly, we have also found a host that is,
to the best of our knowledge, the first synthetic host that
preferentially binds H2AsO4– with respect to H2PO4– [72].
Attempts to extend the use of such hydrogen bond forming
anion receptors to use in ISEs are in progress.
Efficient Use of Receptors in Chemical Sensing Enabled by
Quantitative Response Modeling
The perseverance with which we studied the origin of drifts in the responses of ISEs exposed to
biological samples is typical of our approach. Other studies exemplifying this resulted in the first comprehensive theoretical treatment of the co-ion interference [21], lifetime [34] and selectivity [35] of potentiometric sensors based on electrically charged receptors [45,46]. Also, our quantitative discussion of
multiple complex equilibria occurring in receptor-doped solvent polymeric membranes allowed us to
elucidate the apparently “twice-Nernstian” response slopes [18,27,50,70] of many metalloporphyrin-based sensors [50], which puzzled researchers for more than a decade and prevented a more
systematic and efficient receptor optimization. Later, we extended this response model to give a
generalized explanation of “apparently non-Nernstian” equilibrium responses [55]. Such models are
important for developers of new chemical sensors because they are essential for the understanding of
experimentally observed selectivities and response slopes, the rational design of new receptors, and the
optimum formulation of sensing membranes that result in the highest possible selectivities that may be
achieved with a given receptor.
The importance of thorough mathematical modeling to fully enable sensor optimization is again
illustrated by one of our recent contributions to ISE theory. Few studies of new ISEs appear complete
unless the ratio of ionic sites and ionophore was used to control these stoichiometries and, thereby,
optimize selectivities. It is all the more surprising that the possibility for the simultaneous occurrence of
multiple complexes of the target ion was ignored in the past. In a very recent contribution of ours [93], we
closed a gap in ISE theory. As an example, we reported on the simultaneous formation of 1:1 and 1:2
complexes of a crown ether ionophore, and how this results in response curves with very unusual shapes.
The super-Nernstian responses that we observed were not caused by mass transfer limitations and can be
readily explained with a phase boundary model, a finding that was supported by experimentally
determined complexation constants and excellent fits of response curves. Super-Nernstian responses of
this type are probably not very rare, but lacking
adequate interpretation remained in the past ignored,
misinterpreted, or unreported. We believe that the
proper understanding of this phenomenon will
facilitate the development of new ISEs based on
ionophores that can form complexes of higher
stoichiometries. Since any type of complex with a
stoichiometry higher than 1:1 is formed stepwise
from at least one complex of smaller stoichiometry, it
26
Philippe Buhlmann
appears likely that super-Nernstian responses of this new category are much more common than the
literature suggested in the past. We anticipate that a better theoretical understanding of super-Nernstian
responses will help ISE developers to avoid time-consuming misguided efforts to improve the
selectivities and reproducibility of new ISEs.
Another example where the development of a complex
model involving a series of equilibria was required to fully
elucidate the potentiometric response characteristics is that of a
sulfate ISE based on a guanidinium ionophore. While prior reports
on ISEs based on anion ionophores with guanidine groups existed,
their response mechanism was poorly understood. Our study of the
mono- and dianion responses of such an ISE membrane showed by
theory and confirmed by experiment that Nernstian responses may
result from an electrically neutral or charged ionophore mode when
the ionophore is used in combination with cationic or anionic sites,
respectively [70]. Based on this observation, it might be expected
that membranes without added ionic sites exhibit Nernstian
responses according to a charged carrier mechanism. However,
experimental results show an apparently “two-thirds Nernstian”
equilibrium response, which can be explained on the basis of our
phase boundary model [70]. While host–guest design provides
remarkably sophisticated ionophore, these compounds can only be
put to efficient use if such a complicated response mechanism is fully understood.
Examples where we were not discouraged by puzzling results but insisted on thoroughly understanding the sensor responses also include two studies performed with the exclusive help of undergraduate students [56,61]. In one case, motivated by my previous development of a receptor-based sensor
with good sulfate selectivity [19], we tried to understand the bias that affected the selectivities of a
published sulfate-selective electrode. The receptor re-synthesis and a careful study of the sensor response
revealed that the true receptor was not the zinc complex proposed by the first investigators but a dinuclear
zinc complex. Similarly, the use of a bis-thiourea receptor for anions—developed in extension from our
earlier work with bis-thiourea receptors for measurements of anions in blood serum [9,10,
14,19]—revealed an unusual pH dependence. This resulted in the first observation of non-crystalline,
supramolecular receptor aggregates in solvent polymeric membranes using FTIR microscopy [57]. We
believe that similar aggregates were present in sensing membranes prepared by other investigators
and—unrecognized—made it impossible to explain the relationship between the structure of the receptors
and the selectivity of the corresponding sensor membranes. We are now developing sensors based on
receptors covalently attached to a polymer backbone, preventing this self-aggregation problem.
The above examples illustrate how difficult it can be to make optimized ISEs using ionophores,
which so often are synthesized with great effort. Unfortunately, there is no up-to-date monograph that
discusses the state of the art of practice and theory, which has seen tremendous advances over the past 15
years. After lamenting for years that there was no text that teaches ionophore-based ISEs and related
electrochemical sensors to graduate students and other newcomers to the field (rather than only reviewing
recent developments), I wrote along with graduate student Li Chen a text that discusses the state of the art
of ISEs, including the extension of detection limits from micro- to subpicomolar concentrations,
improvements of selectivities by many orders of magnitude, and major advancements in biocompatibility
and long-term stabilities. It introduces the basic concepts of ISE theory that replaced the empirical
approach of the early ISE history and describes the recently developed concepts for the most efficient use
of these ionophores and ISEs. The text shows not only how ionophores are used in modern potentiometry
to develop new ISEs, but it also illustrates how ionophore-based potentiometry provides the tools to
determine thermodynamic properties of ionophores such as stoichiometries and stabilities of their
complexes using only minimum amounts of ionophore. First tested as accompanying text for my
27
Philippe Buhlmann
electroanalytical course and tutorial for new students of the Buhlmann group, the text has recently been
published [92].
Extension of Fluorous Chemistry to Voltammetric Sensors
Given our success with potentiometric sensors with fluorous
sensing membranes, we were intrigued by the possibility of using
fluorous phases in combination with other electrochemical techniques.
This was not a trivial task since our own work had shown the
exceptionally strong extent of ion pairing in fluorous phases, making such
work difficult even with microelectrodes. Indeed, prior to our own work
voltammetry or amperometry with a fluorous solvent had never been
reported.
Using
the
novel
electrolyte
tetrabutylammonium
tetrakis[3,5-bis(perfluorohexyl)phenyl]borate, we demonstrated the first
cyclic voltammetry in a perfluorocarbon [82]. Even though the solution Fig. 1 CV microcell: (A) Pt
resistance is substantial, the voltammograms could be interpreted and working microelectrode; (B)
fitted with regular theory, which was also confirmed by the measurement Ag/AgCl reference electrode;
(C) Top cap; (D) Glass cell
of diffusion coefficients with 19F DOSY NMR spectroscopy. Importantly, body; (E) Bottom cap; (F) Au
dielectric dispersion spectroscopy verified that addition of the disk auxiliary electrode.
fluorophilic electrolyte does not raise the permittivity of the solution
significantly over what is observed for neat perfluoro(methylcyclohexane). Because fluorous solvents are
the least polar of all liquid phases, we feel that our work represents in some way the ultimate limit of
nonaqueous electrochemistry. From an application point of view, the poor solubility of hydrophobic
species in fluorous phases suggests a whole new field of amperometric sensors in gas and liquid samples
that may be contaminated with fuels, lubricants, or food.
In the course of this voltammetry work with fluorous phases, we realized that while numerous
research laboratories reported that use of small volume cells for voltammetry, surprisingly little explicit
information about microcells is readily available. Small volume adapters are commercially available, but
their use only reduces samples to only ≈2 mL. Moreover, typical microcells are either difficult to
assemble or require the use of microfabrication techniques, making electrode cleaning for repeated use
complicated or impossible. Therefore, we developed a simple electrochemical cell that requires only 200
uL of sample volume. The fabrication and use of this cell is straightforward and easily doable even in an
undergraduate lab, and the cell is cost-effective as it minimizes the use of reagents and waste. While this
cell served us well for our fluorous voltammetry in research performed by undergraduate and graduate
students, we believe that its simplicity and advantages should be also of interest for undergraduate
teaching laboratories, where resources are typically tight and generation of waste is particularly
undesirable. We have accordingly published on this cell in the Journal of Chemical Education [84].
Another topic that arose in connection with fluorous electrochemistry with tetrabutylammonium
tetrakis[3,5-bis(perfluorohexyl)phenyl]borate as the electrolyte salt was the question of how to define the
electrochemical window, i.e., the range of applied voltages in which neither the solvent nor the electrolyte
undergo redox reactions. In the past, the electrochemical limits was typically defined as the potentials at
which a current density of an arbitrary value is obtained. Because different authors use different arbitrary
values, this approach makes it impossible to compare data from different literature sources. We propose a
new method to define the electrochemical limits for a solvent/electrolyte system. It is based on the
realization that at applied potentials at which the electrolyte undergoes a redox reaction, the transport of
electrolyte to the electrode is dominated by migration and not by diffusion. As a result, the current
increases in proportion to the applied potential. Therefore, we propose that the electrochemical limit is
determined by linear extrapolation of the current to its intercept with the x axis in the current-vs-voltage
plot, as it can be obtained from linear sweep voltammetry. To demonstrate our method experimentally, we
determined the reduction potentials for several tetraalkylammonium electrolyte cations. With our new
method, the variation in reduction potential is smaller than 100 mV, while the traditional interpretation
gives a reduction limit for tetramethylammonium that is 300 mV more negative than that for
tetrahexylammonium, a difference that is unrelated to the actual onset of reduction and is affected by the
28
Philippe Buhlmann
kinetics of ion migration. Our method also reduces experimental variability by minimizing the
concentration dependence of the electrochemical limit. For example, use of a 75 mM tetrabutylammonium solution and the conventional method result in a cathodic limit 260 mV more negative than
for a 600 mM solution of the same cation. On the other hand, our proposed method nearly eliminates this
concentration dependence. The use of our new method to determine the width of electrochemical
windows is not only useful for electroanalytical purposes but also for research in other fields of
electrochemistry, such as the development of fuel cells, batteries, and electrochemical supercapacitors.
Meisenheimer Complexes, Job’s Plots, and Voltammetric Sensors for the Detection of Explosives
In an effort to extend our use of synthetic receptors to voltammetric sensors, we developed a
receptor for 2,4-dinitrotoluene (DNT), which is a compound found in all commercial varieties of
2,4,6-trinitrotoluene (TNT). The detection of DNT is of interest because it has a much higher vapor
pressure than TNT and can therefore be detected more readily; indeed, when dogs are trained to find TNT
explosives, they actually smell DNT and not TNT.
In an initial attempt to develop DNT receptors, we focused on charge transfer complexes, as they
have been proposed for many nitroaromatic compounds, including TNT. While none of the aromatic
amines we investigated was found to bind to DNT, we observed a deep blue color for solutions containing
DNT and several alkylamines [89]. Colored complexes of nitroaromatic compounds are well known and
are referred to as σ-complexes (Meisenheimer complexes), which made it deceptively easy to conclude
that this was what caused the color formation in the DNT solutions. However, careful work showed that
caution is warranted to avoid the hasty misidentification of Meisenheimer complexes. 1H NMR spectra
exhibit no significant shifts in the positions of the DNT protons, indicating that the majority of DNT
species in solutions of DNT and amines retain their aromaticity. Density functional calculations on
DNT–ethylamine complexes suggest that Meisenheimer complexes are sufficiently high in free energy so
that they make up only a very small fraction of the full equilibrium population. While principal
component analysis of the UV/Vis spectra of the DNT–amine solutions reveals that only one absorbing
species of significant concentration is formed, quantitative fits of Job’s plots show that 1:1 association of
DNT with the amines alone cannot explain the visible absorption spectra. Instead, the Job’s plots can be
accurately interpreted by deprotonation of DNT, with the amines acting as bases. The deprotonation
equilibria lie far on the side of the unreacted DNT, preventing
the detection by NMR of the deprotonated minority species that
gives the solutions their strong blue color. The analysis of
systems with DNT and n-butylamine, diethylamine,
triethylamine, or benzylamine provides a consistent pKa of DNT
in dimethyl sulfoxide of 15.3±0.2.
We believe that our publication entitled “Interaction of a Weakly Acidic Dinitroaromatic with
Alkylamines: Avoiding the Meisenheimer Trap” that was published in the Journal of the American
Chemical Society is an exemplary case of how to cautiously proceed when dealing with what may be
Meisenheimer complexes, giving it much relevance to a wide audience of readers from different fields of
chemistry in which Meisenheimer complexes play a role (e.g., organic chemistry, analytical chemistry,
biochemistry, toxicology and environmental sciences). Because of the difficulty of using conventional
spectroscopic techniques to study Meisenheimer complexes (or what authors have claimed to be such
complexes), the literature on this topic contains an unusual amount of inconclusive evidence, speculation,
and vague conclusions. We believe that several studies on DNT sensors published in high ranking
journals will need revisiting upon properly considering our results [89].
As mentioned above, we took advantage of Job’s plots in our study of the interaction of DNT and
alkylamines. Job’s plots have been widely utilized to determine the stoichiometry of complexes formed
between two compounds (e.g., A and B). All that is required is to make multiple solutions that contain A
and B in different concentrations, keeping the sum of the concentrations of A and B constant. The
stoichiometry is obtained by the (typically) spectroscopic measurement of the complex concentration. For
example, for 1:1 complexes a maximum in complex concentration is observed in solutions in which the
29
Philippe Buhlmann
total concentration of A equals the one of B, while for 1:2 complexes a maximum in the complex
concentration is observed when the ratio of A and B in solution is 1:2.
While Job’s method has been widely used across
disciplines for almost 100 years, the number of publications
that comment on how to analyze Job’s plots is very limited.
While studying the interaction of DNT and trialkylamines,
we realized that the Job method as used in the past has two
substantial weaknesses. On one hand, it cannot distinguish
between 1:1, 2:2, and 3:3 complexes (or higher analogues).
On the other hand, it cannot distinguish between n:n
complex formation and a reaction in which A and B react to give C and D (i.e., a displacement reaction).
To address this problem, we developed a simple method to analyze Job’s plots. While the underlying
math is rather complicated, the result is a method that requires as little as a pocket calculator and a few
tables that we published in the Journal of Organic Chemistry [90]. In short, the information required to
distinguish between 1:1, 2:2, and higher n:n complexes and to distinguish those from displacement
reactions has been in the Job’s plots readily visible all the time, but surprisingly it has been overlooked
routinely. We applied our new method for the analysis of Job’s plots to our own problem and to several
examples from the literature, illustrating the power of the method [90]. Indeed, we were able to promptly
debunk a misinterpretation of data published in a very reputable journal, giving us confidence that our
method will be useful to researchers who use Job’s plots in many different fields of chemistry (e.g.,
organic, supramolecular chemistry, analytical, inorganic, biochemistry, spectroscopy, pharmacology).
Based on the above described experience, we decided to switch strategy in the design of our DNT
receptor to one based on hydrogen bonding. It was achieved with 3DOM carbon electrodes in which the
pore walls of the 3DOM carbon were modified with DNT
receptors. Square wave voltammetry was used as the
detection mode, resulting in a detection limit of 10 µM for
DNT. A linear response of the electrode when compared to
the logarithm of the concentration of DNT indicated that
receptor-bound DNT was detected rather than DNT in
solution. Moreover, the addition of receptor molecules to
the surface of the 3DOM carbon electrodes provided
selectivity for DNT over interferents. These receptors were
designed to take advantage of the slightly acidic nature of DNT while at the same time including
hydrogen bond-donating sites to further stabilize the deprotonated DNT and thus increase the binding
affinity for DNT [97].
Chemically Selectivity with Scanning Tunneling (STM) Microscopy
Imaging of objects and devices at the molecular level is one of the great challenges of nanotechnology. To observe such structures at the molecular and atomic level with chemical selectivity, we use
STM tips chemically modified with self-assembled monolayers (SAMs), which chemically interact with the
samples of interest during the scanning event. STM revolutionized surface analysis because it allows
imaging with submolecular or atomic resolution in air and liquids, where many other analysis methods
fail. Unfortunately, the limited ability for chemical recognition, i.e., for the discrimination between
different types of atoms or functional groups, is a weakness of STM. However, this problem can be
overcome by allowing an STM tip to interact chemically with a sample. At Tokyo, we introduced the
modification of gold tips with polypyrrole or different types of SAMs for the selective recognition of
functional groups that form hydrogen bonds [17,25,38,40,41]. We showed that this method can be used to
distinguish between different metal centers and between functional groups with different spatial
orientations. The chemical interaction between modified tips and the sample enhances electron transfer
between the tip and sample, resulting in selective recognition of selected functional groups.
30
Philippe Buhlmann
Major problems of this technique were the large fraction of SAM-treated tips that never yielded
chemical selectivity and the relatively short lifetime of modified tips. Experimental data suggest that in
the former case tip-modifying molecules are never present at the end of the tip, while in the latter case
prolonged use of a tip results in the loss of such molecules. In Minneapolis, we showed that the brief
application of a high bias voltage between the sample and the tip causes SAM molecules to reoccupy the
tip apex, thereby allowing the tips to display selective chemical contrast [54]. The useable lifetime of
SAM modified tips could be increased from hours to at least a month. SAM molecules can also be
removed from the tip apex by application of a negative sample bias, making it possible to alternate
between conventional STM images and STM images with chemically enhanced contrasts. Using STM
tips chemically modified with 4-mercaptobenzoic acid, this method was subsequently also applied to
hydrogen bond donating tips, permitting enhanced chemical contrast over oxygen atoms [88].
To improve the reproducibility of tip formation, we also developed a single-step electrochemical
method for producing very sharp gold STM tips [69]. For this purpose, the type and electrolyte was
optimized, showing optimum sharpness of the tips for a NaCl/perchloric acid mixture. These tips are
significantly sharper than those prepared by previously reported single step etching methods, as
confirmed by transmission electron microscopy. Moreover, the etching time was reduced.
To extend chemically selectivity STM imaging based on chemically modified tips to
measurements in aqueous environments, we also developed a method to insulate STM tips on their sides
with a passivating layer of electropaint, leaving only the very end of the STM tip exposed [68]. Since
imaging with samples immersed in aqueous solution is almost always performed under electrochemical
conditions where a well-controlled potential is applied to the sample that is imaged, this technique is
referred to as EC-STM. Tip insulation is necessary for EC-STM because imaging under these conditions
is only possible when the Faradaic currents caused by redox reactions of the solvent and compounds it
contains are small compared to the tunneling current used for imaging. When we started with tip
insulation, we wanted to use EC-STM tips with an insulating coating resistant to organic solvents because
we planned to eventually modify the insulated tips chemically with SAMs and use them for chemically
selective STM imaging of surfaces in electrolyte solutions. The by far most common method for
preparing EC-STM tips, i.e., the coating with nail polish or apiezon wax, was not useful for us since both
nail polish and apiezon wax dissolve in relevant organic solvents. Therefore, we chose to use electropaint
deposition for the tip preparation.
We quickly discovered that the relatively few reports on EC-STM tip preparation by electropaint
deposition were hard to adapt to our problem. A BASF electrodeposition paint used in earlier reports was
not available any more, and published electrodeposition procedures for the preparation of STM tips
proved to be either complicated and very laborious, or hard to reproduce. This led us to study the
parameters of electropaint deposition, and eventually resulted in a remarkably simple method for the fast,
reproducible generation of large numbers of electrically insulated EC-STM tips. Unlike some other papers
on EC-STM tip preparation that were content to measure leakage currents only, we also showed that the
tips are indeed suitable for high resolution EC-STM imaging. We believe that our technique is not only
superior to other published reports on the
preparation of EC-STM tips by deposition of
electropaint, but that our method is also much
easier and less “skill intensive” than nail
polish or apiezon wax coating, which even
frequent EC-STM users describe more as an
art than a science.
This method of EC-STM tip
preparation was subsequently used in our
group to study the adsorption of organic
monolayers onto gold electrodes [83, 94]
since the generation of highly ordered Fig. 1 Molecularly resolved EC-STM images of porphyrin
molecular arrays is of great interest to those adlayers on an Au surface [83].
31
Philippe Buhlmann
pursuing the fabrication of molecular-scale devices and chemically tailored surfaces. We showed the
formation of metalloporphyrin and metal-free porphyrin SAMs by equilibrium adsorption onto an iodine
adlayer on the single crystal surface of Au(111) [94]. The iodine adlayer weakens the porphyrin–substrate
interactions and, thereby, permits formation of highly ordered porphyrin SAMs. Using EC-STM, we
found the CoTPyP and TPyP SAMs to contain highly ordered domains. This was the first
metalloporphyrin to be observed on a halide-modified electrode. We also showed the formation of
porphyrin SAMs by equilibrium adsorption onto a bromine adlayer on Au(111) [83]. As is the case for
iodine too, the bromine adlayer weakens the porphyrin–substrate interactions and, thereby, permits
formation of highly ordered porphyrin SAMs. The wide potential window of usability of the bromine
adlayer extends to potentials more positive than what has been observed for iodine adlayers, which have
been used for most of the prior related work. We expect that other researchers in the field will also switch
over and use bromide adlayers as one of the preferred passivating interlayers in the preparation of various
types of organic monolayers.
References
All references in this research overview refer to Phil Buhlmann’s list of publications.
32
Department of Chemistry
University of Minnesota
Minneapolis MN 55455
E-mail: buhlmann@umn.edu
Office phone: (612) 624-1431
Fax: (612) 626-7541
Philippe Buhlmann
Date of birth: 2 July 1964
Education
• Visiting Professor, Department of Organic and Polymeric Materials, Tokyo Institute of Technology,
Tokyo, Japan, April to July 2009 (Host: Dr. Akira Hirao)
• Postdoctoral Fellow, Department of Chemistry, School of Science, The University of Tokyo, Tokyo,
Japan, 1993–1994 (Advisor: Dr. Yoshio Umezawa)
• PhD in Analytical Chemistry (Dr. sc. nat. ETH), Laboratory of Organic Chemistry, Swiss Federal
Institute of Technology (ETH), Zurich, Switzerland, 1989–1993 (Advisor: Dr. Wilhelm Simon, until
his decease in Nov 1992; interim advisor until Feb 1993: Dr. Ernö Pretsch)
• MSc (Dipl. natw. ETH) in Chemistry, Department of Natural Sciences, Swiss Federal Institute of
Technology (ETH), Zurich, Switzerland, 1984–1989 (Diploma Thesis Advisor: Dr. Joseph Seibl)
•
Employment
• Associate Professor of Chemistry, Dept. of Chemistry, University of Minnesota, Minneapolis, MN,
since Sept. 2006 (Graduate faculty appointments in Chemistry and Chemical Physics)
• Assistant Professor of Chemistry, Department of Chemistry, University of Minnesota, Minneapolis,
MN, September 2000 to August 2006
• Lecturer, Department of Chemistry, Science University of Tokyo, Tokyo, Japan, 1999-2000
• Research Associate, Department of Chemistry, School of Science, The University of Tokyo, Tokyo,
Japan, 1994-2000
• Lecturer, Laboratory of Organic Chemistry, ETH Zurich, Switzerland, 1992
•
Publications
• 94 publications, 2 patents, 1 book (“Structure Determination of Organic Compounds–Tables of
Spectral Data;” translated into German, Spanish, Russian, Japanese, and Chinese; book chapters
downloaded 3550 times in 2011 alone)
• h index 36; publications cited >5900 times (not including >750 citations of “Structure Determination
of Organic Compounds–Tables of Spectral Data”)
•
Professional Awards
•
•
•
•
•
•
Invitation Fellowship from the Japan Society for the Promotion of Science (JSPS, summer 2010)
Research award Nissan Science Foundation (1999)
Research award Tokuyama Science Foundation (1998)
Postdoctoral fellowship, Japan Society for the Promotion of Science (JSPS, 1993)
Postdoctoral fellowship, Swiss National Science Foundation (1993, declined for JSPS fellowship)
2 yr PhD fellowship by the Swiss Chemical Industry Foundation (1990)
•
Professional and Outreach Service
•
•
•
•
Contributing editor Trends in Analytical Chemistry
Associate editor Analytical Sciences
Chief editor SEAC Communications (newsletter of the Society of Electroanalytical Chemistry)
Outreach chair of the Minnesota section of the American Chemical Society; chief organizer of monthly
outreach events Chemists-in-the-Library since 2004
•
Professional Organizations
American Chemical Society (Analytical Chemistry and Fluorine section member), Electrochemical
Society, Society of Electroanalytical Chemistry, Chemical Society of Japan, Fluorine Society of Japan
Current Departmental and University Service
Department of chemistry: director of graduate studies, administrative advisory committee, and temporary
faculty search committee. University senator and member of the university senate library committee and
the committee on academic freedom and tenure.
1
Philippe Buhlmann
List of Publications
• 94 publications, 2 patents, 1 book (“Structure Determination of Organic Compounds–Tables of
Spectral Data;” translated into German, Spanish, Russian, Japanese and Chinese)
• h index 36; publications cited >5900 times (not including >750 citations of “Structure Determination
of Organic Compounds–Tables of Spectral Data”)
Publications Based on PhD and Postdoctoral Studies and as Research Associate at The University
of Tokyo
1. Carrier Based Optodes, Simon, W.; Morf, W. E.; Seiler, K.; Spichiger, U. E.; Haug, J.-P.; Bühlmann,
P., Proc. of the 3rd Int. Meeting on Chemical Sensors, Cleveland, OH, USA, September 24, 1990; p 9
(*)
2. Neutral Hosts for the Complexation of Creatinine, Bühlmann, P.; Simon, W., Tetrahedron 1993, 49,
7627 (****).
3. Molecular Recognition of Creatinine, Bühlmann, P.; Badertscher, M.; Simon, W., Tetrahedron 1993,
49, 595 (****).
4. Optical sensors based on neutral carriers, Spichiger, U. E.; Simon, W.; Bakker, E.; Lerchi, M.;
Bühlmann, P.; Haug, J.-P.; Kuratli, M.; Ozawa, S.; West, S., Sensors and Actuators 1993, 11, 1 (*).
5. Anion Recognition by Neutral Hosts with Urea and Thiourea Functions, Bühlmann, P.; Nishizawa,
S.; Umezawa, Y., "Recent Advances in Inorganic and Organometallic Chemistry", JSPS/NUS Joint
Seminar on Inorganic and Organometallic Chemistry, Tokyo, Japan, December 5-6, 1994 (***).
6. Molecular Resolution Images of a Calix[6]arene from Atomic Force Microscopy, Namba, M.;
Sugawara, M.; Bühlmann, P.; Umezawa, Y., Langmuir 1995, 11, 635 (**).
7. EMF Response of Neutral Carrier Based Ion-Selective Field Effect Transistors with Membranes Free
of Ionic Sites, Bühlmann, P.; Yajima, S.; Tohda, K.; Umezawa, Y., Electrochim. Acta 1995, 40, 3021
(***).
8. Studies on the Phase Boundaries and the Significance of Ionic Sites of Liquid Membrane
Ion-Selective Electrodes, Bühlmann, P.; Yajima, S.; Tohda, K.; Umezawa, K.; Nishizawa, S.;
Umezawa, Y., Electroanalysis 1995, 7, 811 (***).
9. Anion Recognition by Urea and Thiourea Groups: Remarkably Simple Neutral Receptors for
Dihydrogenphosphate, Nishizawa, S.; Bühlmann, P.; Iwao, M.; Umezawa, Y., Tetrahedron Lett.
1995, 36, 6483 (***).
10. A Chloride Ion-Selective Polymeric Membrane Electrode Based on a Hydrogen Bond Forming
Ionophore, Xiao, K. P.; Bühlmann, P.; Nishizawa, S.; Amemiya, S.; Umezawa, Y., Anal. Chem. 1997,
69, 1038 (**).
11. Modification of Silicon Nitride Tips with Trichlorosilane SAMs for Chemical Force Microscopy, Ito,
T.; Namba, M.; Bühlmann, P.; Umezawa, Y., Langmuir 1997, 13, 4323 (**).
12. Channel-Mimetic Sensing Membranes for Nucleotides Based on Multitopic Hydrogen Bonding,
Tohda, K.; Amemiya, S.; Ohki, T.; Nagahora, S.; Tanaka, S.; Bühlmann, P.; Umezawa, Y., Isr. J.
Chem. 1997, 37, 267 (**).
13. Donnan Exclusion Failure of Neutral Ionophore-Based Ion-Selective Electrodes Studied by Optical
Second-Harmonic Generation, Yajima, S.; Tohda, K.; Bühlmann, P.; Umezawa, Y., Anal. Chem.
1997, 69, 1919 (***).
14. Strong Hydrogen Bond-Mediated Complexation of H2PO4- by Neutral Bis-Thiourea Hosts,
Bühlmann, P.; Nishizawa, S.; Xiao, K. P.; Umezawa, Y., Tetrahedron 1997, 53, 1647 (***).
15. Fluorescence Mediated Sensing of Guanosine Derivatives Based on Multitopic Hydrogen Bonding,
Amemiya, S.; Bühlmann, P.; Umezawa, Y., Chem. Commun. 1997, 1027 (***).
16. Hydrogen Bond Based Recognition of Nucleotides by Neutral-Carrier Ion-Selective Electrodes,
Amemiya, S.; Bühlmann, P.; Tohda, K.; Umezawa, Y., Anal. Chim. Acta 1997, 341, 129 (**).
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Philippe Buhlmann
17. Scanning Tunneling Microscopy Using Chemically Modified Tips, Ito, T.; Bühlmann, P.; Umezawa,
Y., Anal. Chem. 1998, 70, 255 (**).
18. A Phase Boundary Model for Apparently "Twice-Nernstian" Responses of Liquid Membrane
Ion-Selective Electrodes, Amemiya, S.; Bühlmann, P.; Umezawa, Y., Anal. Chem. 1998, 70, 445
(***).
19. Application of a Bis-Thiourea Ionophore for an Anion Selective Electrode with a Remarkable Sulfate
Selectivity, Nishizawa, S.; Bühlmann, P.; Xiao, K. P.; Umezawa, Y., Anal. Chim. Acta 1998, 358, 35
(***).
20. Chemical Sensing with Chemically Modified Electrodes that Mimic Gating at Biomembranes
Incorporating Ion-Channel Receptors, Bühlmann, P.; Aoki, H.; Xiao, K. P.; Amemiya, S.; Tohda, K.;
Umezawa, Y., Electroanalysis 1998, 10, 1149 (***).
21. Co-Ion Interference for Ion-Selective Electrodes Based on Charged and Neutral Ionophores: A
Comparison, Bühlmann, P.; Amemiya, S.; Yajima, S.; Umezawa, Y., Anal. Chem. 1998, 70, 4291
(***).
22. Hydrogen-Bonding Ionophores for Inorganic Anions and Nucleotides and Their Application in
Chemical Sensors, Bühlmann, P.; Amemiya, S.; Nishizawa, S.; Xiao, K. P.; Umezawa, Y., J.
Inclusion Phenom. Mol. Recognit. Chem. 1998, 32, 151 (***).
23. Electrochemical Analysis; Sugawara, M.; Bühlmann, P.; Aoki, H.; Tohda, K.; in Experiments in
Analytical Chemistry (in Japanese); Umezawa, Y., Motomizu, S., Watarai, H., Teramae, N., Eds.;
Tokyo Kagaku Dojin: Tokyo, Japan, 1999.
24. Observation of Silver and Hydrogen Ion Binding to Self-Assembled Monolayers with Chemically
Modified AFM Tips, Ito, T.; Citterio, D.; Bühlmann, P.; Umezawa, Y., Langmuir 1999, 15, 2788
(**).
25. Polypyrrole-Modified Tips for Functional Group Recognition in Scanning Tunneling Microscopy,
Ito, T.; Bühlmann, P.; Umezawa, Y., Anal. Chem. 1999, 71, 1699 (**).
26. Self-Assembly of a Tricarboxylate Receptor Through Thioamide Groups and Its Use for
Electrochemical Detection of Protonated Amines, Aoki, H.; Bühlmann, P.; Umezawa, Y., J.
Electroanal. Chem. 1999, 473, 105 (**).
27. Apparently "Non-Nernstian" Equilibrium Responses Based on Complexation Between the Primary
Ion and a Secondary Ion in the Liquid ISE Membrane, Bühlmann, P.; Umezawa, Y., Electroanalysis
1999, 11, 687 (****).
28. Ion-Channel–Mimetic Sensing of Hydrophilic Anions Based on Monolayers of a Hydrogen Bond
Forming Receptor, Xiao, K. P.; Bühlmann, P.; Umezawa, Y., Anal. Chem. 1999, 71, 1183 (**).
29. An Ion-Selective Electrode for Acetate Based on an Urea-Functionalized Porphyrin as a
Hydrogen-Bonding Ionophore, Amemiya, S.; Bühlmann, P.; Umezawa, Y.; Jagessar, R. C.; Burns, D.
H., Anal. Chem. 1999, 71, 1049 (**).
30. Voltammetric Detection of the Polycation Protamine by the Use of Electrodes Modified with
Self-Assembled Monolayers of Thioctic Acid, Gadzekpo, V. P. Y.; Xiao, K. P.; Aoki, H.; Bühlmann,
P.; Umezawa, Y., Anal. Chem. Anal. Chem. 1999, 71, 5109 (**).
31. Electrostatically Induced Inclusion of Anions in Cyclodextrin Monolayers on Electrodes,
Chamberlain, R. V.; Slowinska, K.; Majda, M.; Bühlmann, P.; Aoki, H.; Umezawa, Y., Langmuir
2000, 16, 1388 (***).
32. Ion-Channel–Mimetic Sensors Based on SAMs of Phosphate Esters: High Selectivity for Trivalent
Cations, Takaya, M.; Bühlmann, P.; Umezawa, Y., Mikrochim. Acta 1999, 132, 55 (**).
33. Development of an Ion-Channel Sensor for Heparin Detection., Gadzekpo, V. P. Y.; Bühlmann, P.;
Xiao, K. P.; Aoki, H.; Umezawa, Y., Anal. Chim. Acta 2000, 411, 163 (**).
34. Lifetime of Ion-Selective Electrodes Based on Charged Ionophores, Bühlmann, P.; Umezawa, Y.;
Rondinini, S.; Vertova, A.; Pigliucci, A.; Bertesago, L., Anal. Chem. 2000, 72, 1843 (****).
35. Cationic or Anionic Sites? Selectivity Optimization of Ion-Selective Electrodes Based on Charged
Ionophores, Amemiya, S.; Bühlmann, P.; Pretsch, E.; Rusterholz, B.; Umezawa, Y., Anal. Chem.
2000, 72, 1618 (***).
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Philippe Buhlmann
36. Electrochemical Detection of a One-Base Mismatch in an Oligonucleotide Using Ion-Channel
Sensors With Self-Assembled PNA Monolayers, Aoki, H.; Buhlmann, P.; Umezawa, Y.,
Electroanalysis 2000, 12, 1272 (**).
37. Potentiometric selectivity coefficients of ion-selective electrodes Part I. Inorganic cations, Umezawa,
Y.; Buhlmann, P.; Umezawa, K.; Tohda, K.; Amemiya, S., Pure Appl. Chem. 2000, 72, 1851-2082
(*).
38. Scanning Tunneling Microscopy with Chemically Modified Tips: Discrimination of Porphyrin
Centers Based on Metal Coordination and Hydrogen Bonding, Ohshiro, T.; Ito, T.; Buhlmann, P.;
Umezawa, Y., Anal. Chem. 2001, 73, 1618 (**).
39. Influence of Natural, Electrically Neutral Lipids on the Potentiometric Responses of Cation-Selective
Polymeric Membrane Electrodes, Buhlmann, P.; Hayakawa, M.; Ohshiro, T.; Amemiya, S.;
Umezawa, Y., Anal. Chem. 2001, 73, 3199 (****).
40. Discrimination of Functional Group Recognition with Scanning Tunneling Microscopy Using
Chemically Modified Tips: Recognition of Ether Oxygens Through Hydrogen Bond Interactions,
Nishino, T.; Buhlmann, P.; Ito, T.; Umezawa, Y., Phys. Chem. Chem. Phys. 2001, 3, 1867 (***).
41. Scanning Tunneling Microscopy with Chemically Modified Tips: Orientation-Sensitive Observation
of Ether Oxygens, Nishino, T.; Buhlmann, P.; Ito, T.; Umezawa, Y., Surf. Sci. Lett. 2001, 490, L579
(**).
42. Design and application of ion-channel sensors based on biological and artificial receptors, Sugawara,
M.; Hirano, A.; Buhlmann, P.; Umezawa, Y., Bull. Chem. Soc. Jpn, 2002, 75, 187 (*).
43. Potentiometric selectivity coefficients of ion-selective electrodes part II. Inorganic anions, Umezawa,
Y.; Umezawa, K.; Buhlmann, P.; Hamada, N.; Aoki, Hiroshi; Nakanishi, J.; Sato, M.; Xiao, K. P.;
Nishimura, Y., Pure Appl. Chem. 2002, 74, 923-994 (*).
44. Potentiometric selectivity coefficients of ion-selective electrodes. Part III. Organic ions, Umezawa,
Y.; Buhlmann, P.; Umezawa, K.; Hamada, N., Pure Appl. Chem. 2002, 74, 995-1099 (*).
P. Buhlmann’s relative contributions: PI, principal investigator; * equal contributor, ** project planning,
student advising, manuscript preparation; *** project planning, student advising, manuscript preparation,
performer of experiments; **** project planning, primary performer of experiments, manuscript
preparation
As Independent Investigator at Tokyo
45. Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 1. General Characteristics, Bakker, E.;
Bühlmann, P.; Pretsch, E., Chem. Rev. 1997, 97, 3083 (lesser contributor).
46. Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 2. Ionophores for Potentiometric and
Optical Sensors, Bühlmann, P.; Pretsch, E.; Bakker, E., Chem. Rev. 1998, 98, 1593 (primary
contributor).
47. Chemical Sensors 1997/1998—Ion Sensors, Bühlmann, P., Chem. Sens. 1998, 14, 93.
48. Polymer Membrane Ion-Selective Electrodes—What are the Limits? Bakker, E.; Bühlmann, P.;
Pretsch, E., Electroanalysis 1999, 11, 915 (*).
49. Selectivity of Potentiometric Ion Sensors, Bakker, E.; Ernö Pretsch; Bühlmann, P., Anal. Chem. 2000,
72, 1127 (*).
50. Origin of Non-Nernstian Response Slopes of Metalloporphyrin-Based Liquid/Polymer Membrane
Electrodes, Steinle, E.; Amemiya, S.; Buhlmann, P.; Meyerhoff, M., Anal. Chem. 2000, 72, 5766
(**).
51. Structure Determination of Organic Compounds–Tables of Spectral Data, Pretsch, E.; Bühlmann, P.;
Affolter, C., Springer Verlag: Berlin, Heidelberg, New York, 2000 (*).
{German, Spanish, Chinese, Japanese, and Russian translations published 2001, 2001, 2002, 2004,
and 2004, respectively.}
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Philippe Buhlmann
As Independent Investigator at Minnesota
52. Redox-Active Self-Assembled Monolayers as Novel Solid Contacts for Ion-Selective Electrodes,
Fibbioli, M.; Bandyopadhyay, K.; Liu, S.-G.; Echegoyen, L.; Bourgeois, J.-P.; Enger, O.; Diederich,
F.; Bühlmann, P.; Ernö Pretsch, Chem. Commun. 2000, 339.
53. Redox-Active Self-Assembled Monolayers for Solid-Contact Polymeric Membrane Ion-Selective
Electrodes, Fibbioli, M.; Bandyopadhyay, K.; Liu, S.; Echegoyen, L; Enger, O.; Diederich, F.;
Gingery, D.; Bühlmann, P.; Persson, H.; Suter, U.; Pretsch, E., Chem. Mater. 2002, 14, 1721.
54. Scanning Tunneling Microscopy With Chemically Modified Tips: In-Situ Reestablishment of
Chemical Contrast, Olson, J.; Bühlmann, P., Anal. Chem. 2003, 75, 1089.
55. A Generalized Model for Apparently “Non-Nernstian” Equilibrium Responses of Ionophore-Based
Ion-Selective Electrodes. 1. Independent Complexation of the Ionophore with Primary and Secondary
Ions, Amemiya, S.; Bühlmann, P.; Odashima, K., Anal. Chem. 2003, 75, 3329.
56. Ion-Selective Electrodes for Thiocyanate Based on the Dinuclear Zinc(II) Complex of a
Bis-N,O-bidentate Schiff Base, Bühlmann, P.; Yahya, L.; Enderes, R., Electroanalysis, 2004, 16, 973.
57. Glass and Polymeric Membrane Electrodes for the Measurement of pH in Milk and Cheese, Upreti,
P.; Metzger, L. E.; Bühlmann, P., Talanta, 2004, 63, 139.
58. The phase-boundary potential model, Bakker, E.; Bühlmann, P.; Pretsch, E., Talanta, 2004, 63, 3.
59. Sequential Shape-and-Solder-Directed Self-Assembly of Functional Microsystems, Zheng, W.;
Bühlmann, W.; Jacobs, H. O., Proc. Natl. Acad. Sci. USA, 2004, 10, 12814 (**).
60. Fluorous Bulk Membranes for Potentiometric Sensors with Wide Selectivity Ranges: Observation of
Exceptionally Strong Ion Pair Formation; Boswell, P.; Bühlmann, P. J. Am. Chem. Soc., 2005, 127,
8958.
61. Visible and FTIR Microscopic Observation of Bisthiourea Ionophore Aggregates in Ion-Selective
Electrode Membranes, Phillips, K. N.; Lantz, C.; Bühlmann, P., Electroanalysis, 2005, 17, 2019.
62. Characterization of a Deoxyguanosine Adduct of Tetrachlorobenzoquinone: Dichlorobenzoquinone-1,N2-etheno-2’-deoxyguanosine, Nguyen, T. N. T.; Bertagnolli, A. D.; Villalta, P. W.;
Bühlmann, P.; Sturla, S., Chem. Res. Toxicol., 2005, 18, 1770.
63. Coordinative Properties of Fluorous Solvents with Amino and Ether Groups, Boswell, P. G.; Lugert,
E. C.; Rábai, J.; Amin, E. A., Bühlmann, P., J. Am. Chem. Soc., 2005, 127, 16976.
64. Influence of Calcium and Phosphorus, Lactose, and Salt-to-Moisture Ratio on Cheese Quality: pH
Buffering Properties of Cheese, Upreti, P.; Bühlmann, P., Metzger, L. E., J. Dairy Sci. 2006, 89, 938.
65. Electrochemical Sensors, Bakker, E.; Bühlmann, P.; Pretsch, E., Trends Anal. Chem. 2006, 25, 93.
66. Ion Gels by Self-Assembly of a Triblock Copolymer in an Ionic Liquid, He, Y.; Boswell, P. G.;
Bühlmann, P; Lodge, T. P. J. Phys. Chem., 2007, 111, 4645-4652.
67. Ion-Selective Electrodes with Three-Dimensionally Ordered Macroporous (3DOM) Carbon as Novel
Solid Contact, Lai, C.-Z.; Fierke, M. A.; Stein, A.; Bühlmann, P., Anal. Chem. 2007, 79, 4621-4626.
68. Cathodic Electropaint Insulated Tips for Electrochemical Scanning Tunneling Microscopy,
Thorgaard, S. N.; Bühlmann, P., Anal. Chem. 2007, 79, 9224-9228.
69. Single–Step Electrochemical Method for Producing Very Sharp Au Scanning Tunneling Microscopy
Tips, Gingery, D.; Bühlmann, P., Rev. Sci. Instrumen. 2007, 78, 113703.
70. Response Mechanism of Ion-Selective Electrodes Based on a Guanidine Ionophore: An Apparently
“Two-Thirds Nernstian” Response Slope, Koseoglu, S. S.; Lai, C.-Z.; Ferguson, C.; Bühlmann, P..
Electroanalysis, 2008, 20, 331–339.
71. Plasticization of Amorphous Perfluoropolymers, Lugert, E. C.; Lodge, T. P., Bühlmann, P., J. Polym.
Sci. B.: Polym. Phys. 2008, 46, 516–525.
72. Effect of Spacer Geometry on Oxoanion Binding by Bis- and Tetrakis-Thiourea Hosts, Leung, A. N.;
Degenhardt, D. A.; Bühlmann, P. Tetrahedron 2008, 64, 2530–2536.
73. Fluorophilic Ionophores for Potentiometric pH Determinations with Fluorous Membranes of
Exceptional Selectivity, Boswell, P. G.; Szíjjártó, C.; Jurisch, M.; Gladysz, J.; Rábai, J.; Bühlmann,
P., Anal. Chem. 2008, 80, 2084-2090.
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Philippe Buhlmann
74. Assessment of Density Functionals, Semiempirical Methods, and SCC-DFTB for Protonated
Creatinine Geometries, Settergren, N. M., Bühlmann, P.; Amin, E. A., J. Mol. Struct. Theochem.,
2008, 861, 68–73.
75. Preparation of a Highly Fluorophilic Phosphonium Salt and its Use in a Fluorous Anion-Exchanger
Membrane with High Selectivity for Perfluorinated Acids, Boswell, P. G.; Anfang, A. C.; Bühlmann,
P., J. Fluor. Chem. 2008, 129, 961–967.
76. Formation of gold nanoparticles on multiwalled carbon nanotubes by thermal evaporation, Gingery,
D.; Bühlmann, P., Carbon 2008, 46, 1966–1972.
77. Structure Determination of Organic Compounds–Tables of Spectral Data, Pretsch, E.; Bühlmann, P.;
Badertscher, M., 4th, revised and enlarged edition, Springer Verlag: Berlin, Heidelberg, New York,
2009.
{German translation published 2010.}
78. Subnanomolar Detection Limit Application of Ion-Selective Electrodes with Three-Dimensionally
Ordered Macroporous (3DOM) Carbon Solid Contacts, Lai, C.-Z.; Joyer, M. M.; Fierke, M. A.;
Petkovich, N. D.; Stein, A.; Buhlmann, P., J. Solid State Electrochem 2009, 13, 123–128.
79. Fluorous Polymeric Membranes for Ionophore-Based Ion-Selective Potentiometry, Lai, C.-Z.;
Koseoglu, S. S.; Lugert, E. C.; Boswell, P. G.; Rábai, J.; Lodge, T. P.; Bühlmann, P., J. Am. Chem.
Soc. 2009, 131, 1598–1606.
80. Cation-Coordinating Properties of Perfluoro-15-Crown-5, Lai, C.-Z.; Reardon, M. E.; Boswell, P. G.;
Buhlmann, P., J. Fluor. Chem. 2010, 131, 42–46.
81. Effects of Architecture and Surface Chemistry of Three-Dimensionally Ordered Macroporous Carbon
Solid Contacts on Performance of Ion-Selective Electrodes, Fierke, M. A.; Lai, C.-Z., Bühlmann, P.,
Stein, A., Anal. Chem. 2010, 82, 680–688.
82. Electrochemistry with Media of Exceptionally Low Polarity: Voltammetry in a Fluorous Solvent,
Olson, E. J.; Boswell, P. G.; Givot, B. L.; Yao, L.; Bühlmann, P., J. Electroanal. Chem. 2010, 639,
154–160.
83. Bromine-Passivated Au(111) as a Platform for the Formation of Organic Self-Assembled Monolayers
Under Electrochemical Conditions, Thorgaard, S. N.; Bühlmann, P., Langmuir 2010, 26, 7133–7137.
84. Minimizing Solvent Waste in the Undergraduate Analytical Lab: A Microcell for Cyclic
Voltammetry, Olson, E. J., Bühlmann, P. J. Chem. Ed., 2010, 87, 1260–1261.
85. Chemical Stability and Application of a Fluorophilic Tetraalkylphosphonium Salt in Fluorous
Membrane Anion-Selective Electrodes, Chen, L. D.; Mandal, D.; Gladysz, J. A.; Bühlmann, P., New
J. Chem. 2010, 34, 1867–1874.
86. Redox Potential and C-H Bond Cleaving Properties of a Nonheme FeIV=O Complex in Aqueous
Solution, Wang, D.; Zhang, M.; Bühlmann, P.; Que, L., Jr., J. Am. Chem. Soc. 2010, 132, 7638–7644.
87. Highly Selective Detection of Silver in the Low ppt Range with Ion-Selective Electrodes Based on
Ionophore-Doped Fluorous Membranes, Lai, C.-Z.; Fierke, M. A.; Corrêa da Costa, R.; Gladysz, J.
A.; Stein, A.; Bühlmann, P., Anal. Chem. 2010, 82, 7634–7640.
88. Voltage-induced chemical contrast in scanning tunneling microscopy using tips chemically modified
with hydrogen bond donors, Gingery, D.; Bühlmann, P., Surf. Sci. 2011, 605, 1099–1102.
89. Interaction of a Weakly Acidic Dinitroaromatic with Alkylamines: Avoiding the Meisenheimer Trap,
Olson, E. J.; Xiong, T.; Cramer, C.J.; Bühlmann, P. J. Am. Chem. Soc., 2011, 133, 12858–12865.
90. Getting More Out of a Job Plot: Determination of Reactant:Product Stoichiometry in Cases of
Displacement Reactions and n:n Complex Formation, Olson, E.; Bühlmann, P. J. Org. Chem. 2011,
76, 8406–8412.
91. Potentiometric Sensors Based on Fluorous Membranes with Highly Selective Ionophores for CO32-,
Chen, L. D.; Mandal, D.; Pozzi, G.; Gladysz, J. A.; Bühlmann, P. J. Am. Chem. Soc. 2011, 133,
20869–20877.
92. Ion-Selective Electrodes With Ionophore-Doped Sensing Membranes, Bühlmann, P.; Chen, L. D., in
“Supramolecular Chemistry: From Molecules to Nanomaterials, Steed, J. W. and Gale, P. A., eds.,
John Wiley & Sons (Chichester, UK), 2012, 2539–2580.
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Philippe Buhlmann
93. Ion-Selective Electrodes with Unusual Response Functions: Simultaneous Formation of
Ionophore–Primary Ion Complexes with Different Stoichiometries, Miyake, M.; Chen, L. D.; Pozzi,
G.; Bühlmann, P. Anal. Chem., 2012, 84, 1104–1111.
94. Self-Assembled Monolayers Formed by 5,10,15,20-Tetra(4-pyridyl)porphyrin and Cobalt
5,10,15,20-Tetra(4-pyridyl)-21H,23H-Porphine on Iodine-Passivated Au(111) as Observed Using
Electrochemical Scanning Tunneling Microscopy and Cyclic Voltammetry, Thorgaard, S. N.;
Bühlmann, P., J. Electroanal. Chem. 2012, 664, 94–99.Fluorous Membrane Ion-Selective Electrodes
for Perfluorinated Surfactants: Trace Level Detection and In-Situ Monitoring of Adsorption onto
Sand; Chen, L. D. ; Lai, C.-Z. ; Granda, L. P. ; Fierke, M. ; Mandal, D.; Stein, A.; Gladysz, J. A.;
Bühlmann, P., submission 12 May 2012.
96. Ionic Liquid Reference Electrode with Three-Dimensionally Ordered Macroporous Carbon as the
Solid Contact for Long-Term Stability, Zhang, T.; Lai, C.-Z.; Fierke, M.; Stein, A.; Bühlmann, P.
resubmission 8 June 2012.
97. Receptor-Based Detection of 2,4-Dinitrotoluene using Modified Three-Dimensionally Ordered
Macroporous Carbon Electrodes, Fierke, M.; Olson, E. J., Bühlmann, P.; Stein, A. submission 19
June 2012.
98. A Highly Selective Cyanide-Selective Electrode Based on Zn(II) Tetraphenylporphyrin as Ionophore,
Chen, L. D.; Bühlmann, P., submission 9 July 2012.
Patents
As Independent Investigator at Minnesota
Boswell, P.; Buhlmann, P. “Chemical Sensor”, US Patent, May 23, 2006 (P. Buhlmann’s role: principal
investigator). Patent successfully licensed by UofMN to United Science in 2011.
Buhlmann, P.; Thompson, J.; Chen, L.; Settergren, N. “Membrane Based Ion Selective Electrodes for
Flotation Collector and Additive Measurement and Control”, provisional US Patent Application, July 14,
2010 (P. Buhlmann’s role: principal investigator).
Invited Talks
Prior to Minnesota
1. Chemical Sensing Based on Self-Assembled Cyclodextrin Monolayers, Bühlmann, P.; Aoki, H.;
Umezawa, Y.; Chamberlain, R.; Majda, M., 9th Meeting of the Materials Research Society of Japan
(MRS-J), Kawasaki, Japan; 11–12 December 1997
2. Anion Recognition by Neutral, Hydrogen-bonding Ionophores, Bühlmann, P., 13th Meeting of the
Society for Functional Host–Guest Chemistry, Yokohama, Japan; 26 March 1997
3. Anionenselektive Elektroden auf der Basis von Wasserstoffbrückenbildenden Ionophoren, Bühlmann,
P., Analytical Chemistry Colloquium, Swiss Federal Institute of Technology, Zurich, Switzerland; 9
January 1997
4. Scanning Tunneling Microscopy based on Chemically Modified Tips, Bühlmann, P., Meeting of the
National Institute of Genetics, Mishima, Japan; 16 July 1998
5. Scanning Tunneling Microscopy with Chemically Modified Tips, Bühlmann, P., Analytical
Chemistry Colloquium, Swiss Federal Institute of Technology, Zurich, Switzerland; January 2000
6. Ion-channel-mimetic Sensing with Ionophore-based Electrodes, Bühlmann, P., Pittsburgh Conference
of Analytical Chemistry, New Orleans, LI, USA, March, 2000
7. Scanning Tunneling Microscopy Using Chemically Modified Tips, Bühlmann, P., 4th Symposium on
Functional Structure and Analytical Chemistry, Sendai, Japan, 1 July, 2000
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Philippe Buhlmann
As Independent Investigator at Minnesota
8. Scanning Tunneling Microscopy with Chemically Modified Tips: Chemically Selective
Characterization of Nanomaterials, Bühlmann, P., 33rd Great Lakes/Central Regional Meeting of the
American Chemical Society, Grand Rapids, MI, USA, June 11-13, 2001
9. Electroanalytical Sensors Based on Redox-Ionophores, Bühlmann, P.; Lor, S., International Congress
on Analytical Sciences, Tokyo, Japan, August 6-10, 2001
10. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., University of Manitoba, Winnipeg,
1 March 2002
11. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., University of Winnipeg, Winnipeg,
4 March 2002
12. Chemically Modified Tips for Chemically Selective Imaging in Scanning Tunneling Microscopy;
Bühlmann, P., Department of Chemistry, University of Michigan, March 28, 2002
13. Selectivity of a Binuclear Zinc Ionophore, Bühlmann, P.; Enderes, R.; Yahya, L., International
Conference on Electrochemical Sensors, Mátrafüred, Hungary, October 13-18, 2002
14. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Gustavus Adolphus College, St.
Peter MN, 1 November 2002
15. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Winona State University, Winona
MN, 15 November 2002
16. New sensing mechanisms for improving detection limits, Bühlmann, P., Pittsburgh Conference of
Analytical Chemistry, Orlando, FL, USA, March 9-14, 2003
17. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Montana State University, Bozeman
MT, 28 March 2003
18. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Hamline University, St. Paul MN, 9
May 2003
19. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Great Lakes Regional Meeting of
the American Chemical Society, Chicago, IL, United States, May 31-June 2, 2003.
20. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., University of Wisconsin,
Milwaukee WI, October 17, 2003
21. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Auburn University, Auburn AL,
November 6, 2003
22. Electrochemistry with Fluorous Phases, Bühlmann, P., 37th Heyrovsky Discussion on Emerging
Topics, Applications and Methodologies in Electrochemistry, Castle Trest, Czech Republic, June
13–17, 2004
23. Chemically Selective Imaging with Scanning Tunneling Microscopy Using Chemically Modified
Tips, Bühlmann, P., Centre for Chemical Sensors, Swiss Federal Institute of Technology, Zurich,
Switzerland, June 18, 2004
24. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Bethel University, St. Paul MN, 15
November 2004
25. Chemically Selective Imaging with Scanning Tunneling Microscopy Using Chemically Modified
Tips, Bühlmann, P., NanoIGERT seminar, University of Minnesota, Minneapolis MN, December 10,
2004
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26. Perfluorinated Matrixes as New Materials for Receptor-Doped Chemical Sensors, Bühlmann, P.;
Boswell, P.; Lugert, E., ACS spring meeting 2005, San Diego, March 13-17, 2005
27. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., Minnesota State University,
Moorhead MN, 8 April 2005
28. Molecular Recognition in Electroanalytical Chemistry: From Chemical Sensors to Scanning
Tunneling Microscopy with Chemical Selectivity, Bühlmann, P., University of Minnesota, Duluth
MN, 22 April 2005
29. Short Course “Electrochemical Sensors”, Bühlmann, P., Short Course “Electrochemical Sensors”,
International Society of Electrochemistry 2005 meeting, Busan, South Korea, September 25–30, 2005
30. Chemical Sensing with Fluorous Sensing Membranes: A Novel Approach to Reduce Biofouling,
Bühlmann, P., Session “Analytical Electrochemistry”, International Society of Electrochemistry 2005
meeting, Busan, South Korea, September 25–30, 2005.
31. Electrochemistry with Fluorous Phases: Testing the Limits of Low Polarity, Bühlmann, P.,
Department of Organic Chemistry, Eötvös Loránd University, Budapest, Hungary, November 2005.
32. Molecular Recognition at Self-Assembled Monolayers: From Electrochemical Sensors to Surface
Characterization at the Molecular Level, Bühlmann, P., Department of Chemistry, Hefei University,
Hefei, China, May 29, 2006.
33. Chemical Sensors Based on Fluorous Phases: A New Approach to Biocompatibility: Bühlmann, P.,
Department of Chemistry, Hefei University, Hefei, China, May 29, 2006.
34. Chemical Sensors Based on Fluorous Phases: A New Approach to Biocompatibility, Bühlmann, P.,
Department of Chemistry, Renmin University of China, Beijing, China, June 2, 2006.
35. Chemical Sensors Based on Fluorous Phases: A New Approach to Biocompatibility, Bühlmann, P.,
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry,
Chinese Academy of Sciences, Changchun, China, June 5, 2006.
36. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Challenges of Working with
Phases of Extremely Low Polarity to Biocompatibility, Bühlmann, P.,Gordon Conference on
Electrochemistry, Ventura CA, January 14-19, 2007.
37. Receptor-Based Chemical Sensors Based on Fluorous Membranes: Unique Selectivities and
Robustness, Bühlmann, P., The Pittsburgh Conference, Chicago, February 25–March 1, 2007.
38. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Challenges of Working with
Phases of Extremely Low Polarity to Biocompatibility, Bühlmann, P., Department of Chemistry,
Creighton University, Omaha NE, March 22, 2007.
39. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Challenges of Working with
Phases of Extremely Low Polarity to Biocompatibility, Bühlmann, P., Department of Chemistry,
University of North Carolina at Chapel Hill, Chapel Hill NC, April 9, 2007.
40. What Should be Reported to Characterize Solid-Contacted Electrodes?, Bühlmann, P., Development
and Application Chemical Sensors, Bühlmann, P., Meeting of the Analytical Chemistry Section of the
Swiss Chemical Society and the Center of Excellence in Analytical Chemistry, Zürich, Switzerland,
June 28-29, 2007.
41. Electrochemical Sensors Based on Polymeric Fluorous Phases, Bühlmann, P., Schlumberger
Cambridge Research Center, Cambridge, UK, July 2, 2007.
42. Fluorous Receptor-doped Sensing Membranes for Clinical and Environmental Monitoring,
Bühlmann, P., 2nd International Symposium on Fluorous Technologies (ISOFT 07), Yokohama,
Japan, July 30–August 1, 2007.
43. Fluorous Receptor-doped Sensing Membranes for Clinical and Environmental Monitoring,
Bühlmann, P., Honeywell Automation and Control Solutions 2007 Fellows Symposium, Minneapolis,
October 2–3, 2007.
44. Potentiometric Ionophore-Based Sensors with Three-Dimensionally Ordered Nanoporous (3DOM)
Carbon as Novel Solid Contact, Bühlmann, P., 3rd Annual Minnesota Nanotechnology
Conference November 13 - 14, 2007.
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45. Electrochemical Sensors for Biological and Environmental Applications, Bühlmann, P., Process
Chemistry Centre, Åbo Akademi University, Turku, Finland, February 7, 2008.
46. Pushing the Limits of Biofouling Resistance and Longterm Stability: Receptor-Based Sensing
Membranes Based on Fluorous Phases on Nanoporous Carbon, Bühlmann, P., Process Chemistry
Centre, Åbo Akademi University, Turku, Finland, February 8, 2008.
47. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Ultimate Limits of
Nonpolarity to Biocompatibility, Bühlmann, P., Department of Chemistry, Hope College, Holland
MI, 11 April 2008.
48. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Ultimate Limits of
Nonpolarity to Biocompatibility, Bühlmann, P., Minnesota Section of the American Chemical
Society, Eagan MN, 15 October 2008.
49. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Ultimate Limits of
Nonpolarity to Biocompatibility, Bühlmann, P., Gustavus Adolphus College, St. Peter MN, 7
November 2008.
50. Chemical Sensors with Fluorous Membranes: From Fluorous Liquids to Fluorous Polymeric Phases,
Bühlmann, P., 19th Winter Fluorine Conference, St. Petersburg Beach FL, January 11–16, 2009.
51. Electrochemical Sensing With Receptor-Doped Perfluoropolymer Membranes: Fluorous Phases as
the Ultimate Limit of Low Polarity? Bühlmann, P., Department of Chemistry, University of Utah,
February 2, 2009.
52. Electrochemical Sensors Based on Perfluoropolymer Membranes: From the Ultimate Limits of
Nonpolarity to Biocompatibility, Bühlmann, P., Materials Research Center, Department of Materials,
Swiss Federal Institute of Technology, Zürich, Switzerland, 11 February 2009.
53. Electrochemical Sensors for Biological and Environmental Applications, Bühlmann, P., National
Research Center, Cairo, Egypt, 23 February 2009.
54. Electrochemical Sensors Based on Polymeric Fluorous Phases and Nanoporous Carbon: From the
Ultimate Limits of Nonpolarity to Biocompatibility and Long-Term Stability, Bühlmann, P., National
Research Center, Cairo, Egypt, 23 February 2009.
55. Electrochemical Sensors Based on Polymeric Fluorous Phases: From the Ultimate Limits of
Nonpolarity to Biocompatibility, Bühlmann, P., Tokyo Institute of Technology, Tokyo, Japan, 20
April 2009.
56. Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., Toyohashi University, Toyohashi, Japan, 12 June 2009.
57. Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., Yamagata University, Yonezawa, Japan, 18 June 2009.
58. Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., Hokkaido University, Sapporo, Japan, 25 June 2009.
59. Chemical Sensors Based On Receptor-Doped Fluorous Membranes, Bühlmann, P., joint meeting 3rd
International Symposium on Fluorous Technologies and 19th International Symposium on Fluorine
Chemistry 2009, Jackson Hole WY, August 23–28, 2009.
60. Fluoropolymers for Chemical Sensing, Bühlmann, P., 2009 International Symposium on Nano
Structures: Synthesis, Characterization and Application, Gwangju, Korea, 9 October 2009.
61. Ion Sensors Based on Receptor-Doped Perfluoropolymer Membranes: Reduction in Chemical
Fouling and Increase in Robustness, Bühlmann, P., Newmont Metallurgical Services, Englewood,
Colorado, November 6, 2009.
62. Chemical Sensing Based on Electrochemistry in Fluorous Phases, Bühlmann, P., Analytical Seminar,
Department of Chemistry, University of Minnesota, November 13, 2009.
63. Electrochemistry with Fluorous Phases and Three-Dimensionally Ordered Marcoproous Carbon,
Bühlmann, P., Faculty Lunch Seminar, Department of Chemistry, University of Minnesota, March
30, 2010.
64. Chemical Sensors based on Electrochemistry with Fluorous Phases: From the Ultimate Limits of Low
Polarity to Extreme Selectivities and Detection Limits, Bühlmann, P., Department of Energy and
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Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan, July 2,
2010.
Chemical Sensors based on Electrochemistry with Fluorous Phases: From the Ultimate Limits of Low
Polarity to Extreme Selectivities and Detection Limits, Bühlmann, P., Hosei University,
Higashi-Koganei, Tokyo, Japan, July 8, 2010.
Chemical Sensors based on Electrochemistry with Fluorous Phases: From the Ultimate Limits of Low
Polarity to Extreme Selectivities and Detection Limits, Bühlmann, P., Tohoku University, Sendai,
Japan, July 9, 2010.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility, 117th
G-COE Seminar, Bühlmann, P., Kyushu University, Fukuoka, Japan, July 13, 2010.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., Nihon University, Ochanomizu, Tokyo, Japan, July 22, 2010.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., Carleton College, Northfield MN, 5 November 2010.
Three-Dimensionally Ordered Macroporous Carbon as Novel Solid Contacts for Ion-Selective
Electrodes, Bühlmann, P., Lai, C.-Z.; Fierke, M. A.; Stein, A., Japan-USA Minisymposium on
Molecular Simulation Meets Material Science, Hawaii University, Honolulu HI, December 16, 2010.
Receptor-Based Ion Recognition in Fluorous Phases, Bühlmann, P., 2010 International Chemical
Congress of Pacific Basin Societies (Pacifichem), Honolulu HI, December 15–20, 2010.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., Saint Cloud State University, Saint Cloud MN, 30 March 2011.
Potentiometric Sensors with Fluorous Membranes: New Materials that Push the Limits of Selectivity,
Detection Limits, and Theory, Bühlmann, P., IUPAC International Congress on Analytical Sciences
2011, Kyoto, Japan, May 22–26, 2011.
Carbonate Sensors Based on Receptor-Doped Perfluoropolymers: A Major Improvement over
Trifluoroacetophenones, Chen, L. D., Pozzi, G.; Buhlmann, P., Bühlmann, P., IUPAC International
Congress on Analytical Sciences 2011, Kyoto, Japan, May 22–26, 2011.
Ionophore-Based Reference Electrodes Operated in a Current Pulse Mode, Zou, X. U., Bühlmann, P.,
Shikata Discussion 2011, Awaji-Shima, Japan, May 27–29, 2011.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Electrochemical Sensors
with Exceptional Selectivities and Detection Limits, Bühlmann, P., University of Pittsburgh,
November 3, 2011.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., University of South Dakota, Vermillion, November 7, 2011
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility, The
University of Tokyo, Tokyo, Japan, 29 June 2012.
Innovative Electrochemistry Based on Ionophores, Bühlmann, P., Keio University, Yokohama, Japan,
30 June 2012.
Polymeric Fluorous Phases: From the Ultimate Limits of Low Polarity to Biocompatibility,
Bühlmann, P., University of Cincinnati, 31 July 2012.
TBA, Bühlmann, P., Case Western University, 3 August 2012.
Electrochemistry in the Undergraduate Analytical Lab: From Minimizing Solvent Waste to
Environmental Analysis, Bühlmann, P.; Olson, E. J., Biennial Conference on Chemical Education,
Pennsylvania State University, University Park PA, August 1, 2012.
TBA, Bühlmann, P., Macalester College, Saint Paul MN, September 19, 2012.
Fluorous-Membrane Chemical Sensors: From the Ultimate Limits of Low Polarity to
Biocompatibility and Nanotoxicity Measurements, Bühlmann, P., Tufts University, Boston MA, 2
October 2012.
TBA, Bühlmann, P., Augsburg College, Minneapolis MN, fall 2012.
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Philippe Buhlmann
Contributed Talks
Prior to Minnesota
24 contributed talks as presenting author between 1991 and 2000.
As Independent Investigator at Minnesota
1. Incorporation of Redox-Active Ionophores into Solvent Polymeric Membranes, Bühlmann, P., The
Pittsburgh Conference, New Orleans, 5-8 March, 2001.
2. Scanning Tunneling Microscopy with Chemical Selectivity by Chemical Tip Modification,
Bühlmann, P., Midwest University Analytical Chemistry Conference, St. Paul, MN, USA, October
19, 2001.
3. Incorporation of Redox-Active Ionophores into Solvent Polymeric Membranes, Bühlmann, P., The
Pittsburgh Conference, New Orleans, March 17-22, 2002.
4. Anion-Selective Electrodes Based on Thiourea Ionophores, Bühlmann, P., Pittsburgh Conference of
Analytical Chemistry, Orlando, FL, USA, March 9-14, 2003
5. Supramolecular Ionophore Assembly in Solvent Polymeric Ion-Selective Membranes as Observed by
UV/Vis and FTIR Microscopy, Phillips, K.; Lantz, C.; Bühlmann, P., The Pittsburgh Conference,
Chicago, March 9, 2004.
6. Direct Measurements with Ionophore-Based Ion-Selective Electrodes in Dairy Products and Other
Lipid-Containing Samples, Upreti, P.; Caperton, R.; Metzger, L.; Bühlmann, P., The Pittsburgh
Conference, Chicago, March 9, 2004.
7. Perfluorinated Matrixes as New Materials for Receptor-Doped Chemical Sensors with Extreme
Robustness and Selectivity, Bühlmann, P., Midwest University Analytical Chemistry Conference,
Columbus, OH, USA, October 14, 2004.
8. Perfluorinated Matrixes as New Materials for Receptor-Doped Chemical Sensors with Extreme
Robustness and Selectivity, Boswell, P.; Bühlmann, P., The Pittsburgh Conference, Orlando,
February 27–March 3, 2005.
9. Electrochemistry With Fluorous Phases: Testing the Limits of Low Polarity, Bühlmann P.; Boswell,
P. G.; Lugert, E. C.; Rabai, J., International Conference on Electrochemical Sensors, Mátrafüred,
Hungary, November 13-18, 2005
10. Fluorous membranes for receptor-doped chemical sensors with high robustness and selectivity,
Bühlmann, P.; Boswell, P.; Lugert, E., Pacifichem 2005, Honolulu HI, December 15-20, 2005.
11. Boswell, P. G.; Lugert, E. C.; Rabai, J.; Amin, E. A.; Bühlmann, P., “Fluorous Ion-Exchanger and
Ionophore-Doped Ion-Selective Electrodes Exhibiting High Selectivities and Wide Working
Concentration Ranges”, Pittsburgh Conference of Analytical Chemistry & Applied Spectroscopy
2006 (Pittcon 2006), Orlando, FL, March 12-17, 2006.
12. Ionophore-Doped Ion-Selective Electrodes (ISEs) with Perfluorinated Polymeric Matrixes,
Bühlmann, P., Boswell, P. G.; Lai, C.-Z.; Lugert, E. C.; Leung, A. N., The Pittsburgh Conference,
New Orleans, March 1–8, 2008.
13. Receptor-based Chemical Sensors with Fluorous Polymeric Matrixes, Bühlmann, P.; Lai, C.-Z.;
Lugert, E. C., The Pittsburgh Conference, New Orleans, March 8–13, 2009.
14. Novel Approaches to that Pesky Reference Electrode Problem, Bühlmann, P., Midwestern
Universities Analytical Chemistry Conference, Purdue University, West Lafayette IN, October 7–9,
2010.
15. Three-Dimensionally Ordered Macroporous (3DOM) Carbon and Fluorous Phases: Highly Selective
Potentiometric Measurements of Heavy Metals and Perfluorocarboxylates in the ppb and ppt Range,
Bühlmann, P.; Lai, C.-Z. 1; Fierke, M. A.; Stein, A., 2010 International Chemical Congress of Pacific
Basin Societies (Pacifichem), Honolulu HI, December 15–20, 2010.
16. Novel Approaches to that Reference Electrode Problem, Bühlmann, P., Chen, L. D.; Zhan, T.; Zou,
X. U., The Pittsburgh Conference, Atlanta, March 13–17, 2011.
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17. Evaluation of a Novel Xanthate ISE for Froth Flotation, Settergren, N.; Chen, L. D.; Buhlmann, P.;
Thompson, J.; Lugert, E.; Kutz, K.; Lai, C.-Z.; Jeseritz, D., 2011 Society for Mining, Metallurgy, and
Exploration, Denver CO, February 27–March 2, 2011.
18. Ion-Selective Electrodes Based on Fluorophilic Crown Ethers and Mn(III) Salen Complexes: Why
Current Response Models can Still Benefit from Further Development, Bühlmann, P., International
Conference on Electrochemical Sensors, Mátrafüred, Hungary, June 19–24, 2011.
19. Advantages and Limitations of a Reference Electrodes based on an Ionic Liquid, Zhang, T.; Lai,
C.-Z.; Fierke, M.; Stein, A.; Bühlmann, P., The Pittsburgh Conference, Orlando, March 11–15, 2012.
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