Elsevier

Analytica Chimica Acta

Volume 504, Issue 1, 16 February 2004, Pages 113-122
Analytica Chimica Acta

Development of ion-sensitive field-effect transistor-based sensors for benzylphosphonic acids and thiophenols using molecularly imprinted TiO2 films

https://doi.org/10.1016/S0003-2670(03)00532-4Get rights and content

Abstract

Molecularly imprinted polymeric membranes, containing artificial recognition sites for a number of benzylphosphonic acid derivatives, were prepared by the polymerization of titanium(IV) butoxide in the presence of a titanium(IV) phosphonate complex. Reference polymers were prepared in the same manner but in the absence of the phosphonate template. FTIR spectroscopy was used to follow the formation of a benzylphosphonic acid–Titanium(IV) oxide complex during the imprinting process, and upon the association of the substrate in the imprinted TiO2 thin film. The imprinted polymers were examined as sensing membranes in an ion-sensitive field-effect transistors (ISFETs). The sensors reveal selectivity towards analyzing the imprinted substrates, yet the recognition ability of the sensors strongly depends on the substituents associated with the phosphonic acid structures. The response time of the sensors is ca. 45 s, and the sensors reveal unaffected stability for at least 2 weeks. Also, imprinted TiO2 films for thiophenol, and para-nitrothiophenol were generated on ISFET devices, and the respective substrates were selectively sensed by the functional devices.

Introduction

Substantial research activities are directed to the development of specific simple, cheap and miniaturized sensing devices. Biosensors provide very specific sensors as a result of specific recognition properties of complementary biological interactions. They suffer however from stability limitations, and are limited to substrates recognized by biomaterials [1]. Chemical sensors are anticipated to reveal substantially higher stabilities and eventually would be applicable for the sensing of biologically non-compatible substrates, but are expected to exhibit lower specificity and selectivity features. Recent scientific efforts are directed to developing specific host–guest complexes stabilized by supramolecular interactions [2], [3]. The incorporation of chemical entities capable of forming specific supramolecular complexes into polymer matrices could lead to selective functional membranes for sensing applications.

Synthetic polymer matrices that include pre-designed recognition sites provide interesting interfaces for sensor devices. Polymers that include receptor units such as crown-ethers [4], cyclodextrins [5] or other recognition sites [4], [6] have been employed as active sensing interfaces. Imprinted polymers provide a very general class of sensing matrices that include pre-designed recognition sites [7], [8], [9]. The imprinting procedure of molecular recognition sites in polymers represents the chemist’s approach to an evolutionary process to tailor recognition sites mimicking the biological formation of tailored antibodies [10], [11]. The imprinting of the polymers with molecular recognition sites involves the fabrication of a polymer that includes a template molecular structure. The removal of the molecular template from the polymer structure generates structural contours for the selective binding and accommodation of the released molecule. The generation of the imprinted polymers with selective recognition sites requires the incorporation of chemical functionalities to the polymer backbone that bind the substrate, and a delicate crosslinking degree of the polymer that yields rigid imprinted molecular contours, yet sufficiently permeable to allow the rapid association to the imprinted sites. Two general approaches were employed to generate imprinted sites in polymers. By one approach, monomers that include complementary functional groups to the imprinted molecule, e.g. H-bonds, electrostatic interaction, π–π and donor–acceptor interactions are copolymerized and crosslinked in the presence of the imprinted substrate [12], [13]. Removal of the imprinted substrate by a washing process results in the formation of the imprinted molecular contours in the polymer. The second approach to generate the imprinted polymers involves the covalent attachment [14] or coordination of the substrate [15] to polymerizable groups. The polymerization of the functional monomers in the presence of other monomers under crosslinking conditions yields a copolymer in which the imprinted substrate is linked to the polymer by cleavable bonds. The subsequent chemical cleavage of the bound molecular units yield the imprinted polymer with the specific recognition sites. Imprinted polymers were extensively used as separation matrices [16] and as selective catalytic polymers [17], and the different uses of imprinted polymers were reviewed [18], [19], [20].

The use of imprinted polymers as active specific sensing matrices is particularly tempting since pre-designed recognition sites may be architectured in the polymer. The use of imprinted polymers as active sensing interfaces is, however, quite limited until now. Several factors limit the use of imprinted polymers in sensor devices: (i) The concentration of imprinted recognition sites per unit volume of the polymer is relatively low. Thus, to achieve satisfactory sensitivities, relatively thick polymer matrices are required. This introduces diffusion barriers of the substrates to the imprinted sites and relatively slow response times. (ii) In order to develop a sensor device, the integration of the imprinted polymer with electronic transducers is required. The substrates that bind to the imprinted molecular recognition sites usually do not communicate with the electronic transducer, leading to the failure of the device. Thus, for the assembly of electronic sensors based on molecularly imprinted polymers, it is advantageous to design systems that include thin polymer matrices that communicate with the electronic transducer to the extent that the binding of the host substrate to the imprinted sites is sufficient to activate the electronic transducer to yield a readable signal that reflects the bonding event to the sensing interface. Most of the sensors based on imprinted polymers are optical and include chromogenic markers [21] or fluorescence dyes [22]. Several studies have employed microgravimetric quartz crystal microbalance (QCM) measurements that followed mass changes associated with the binding of the substrate to the imprinted sites [23], [24]. Recently, the swelling of imprinted hydrogels resulting in upon association of the substrate, was reported to develop quartz crystal microbalance sensors [25] and surface plasmon resonance (SPR) sensors [26].

The use of ion-sensitive field-effect transistors (ISFETs) as electronic transducing elements of molecular recognition events in imprinted polymers could reveal important analytical advantages due to intrinsic high sensitivities, miniaturization capability, and cost effectiveness. Recently, imprinted polymer membranes that alter the ISFET gate potential upon the binding of the substrates to the imprinted sites, were employed to develop sensors, e.g. for nucleotides [25]. Also, imprinted TiO2 films assembled on ISFET devices were used to develop highly specific electronic sensors for chloroaromatic acids [27]. It was demonstrated that chiroselective [28] and stereoselective [29] imprinted TiO2 films could be assembled on the ISFET devices for a variety of chiral carboxylic acids and for structural isomers of carboxylic acids. In all of these systems a TiO2 imprinted film that is associated with the gate surface of the ISFET is generated by the sol–gel deposition of the Ti(IV)–carboxylate complex on the gate interface. The subsequent elimination of the carboxylate yields the molecular contours of the carboxylate in the TiO2 film and generates a Ti(IV)-OH site that undergoes dissociation that controls the gate potential. Thus, re-binding of the carboxylate to the imprinted sites can be electronically transduced by the functional ISFET device.

Here we wish to report on the integration of imprinted TiO2 films with ISFET devices for the analysis of benzylphosphonic acid and thiophenol derivatives. We address the fabrication of the imprinted membranes on the ISFET devices, and discuss the selectivity of the imprinted membranes.

Section snippets

Materials

Benzylphosphonic acid was purchased from Aldrich and its derivatives, p-CF3, -Br and -NO2, were synthesized as described below.

Titanium(IV) butoxide was purchased from Aldrich. All other chemicals (Sigma or Aldrich) were of analytical grade and used as supplied. Ultrapure water from Serapur PRO90CN was used throughout all the experiments.

General procedure for the preparation of the benzylphosphonic acids

The respective para-substituted benzyl bromide and triethyl phosphite (2 eq.) were placed in a round-bottomed flask equipped with a magnetic stirring bar and an

Results and discussion

Fig. 1 outlines the method to prepare the imprinted recognition sites for the phosphonic acids substrates in a TiO2 polymer thin film acting as the sensing interface on the ISFET gate. The structures of the different substrates imprinted in the films are also depicted in the Fig. 1. The imprinting of the phosphonic acid substrates in the TiO2 film associated with the ISFET gate is accomplished by the sol–gel polymerization of Ti(IV)-butoxide in the presence of the Ti(IV)–phosphonate complex

Conclusions

The present paper has demonstrated the imprinting of molecular recognition sites for benzylphosphonic acid derivatives and thiolated substrates in TiO2 films associated with ISFET devices. Phosphonic acid derivatives are common pollutants originating from the detergent industries [37]. Mercaptans are pollutants originating from oil refineries and other chemical plants, e.g. herbicide manufacturers. The present study introduces inorganic imprinted matrices that may be applied for the separation

Acknowledgements

This research was supported by The Israel Ministry of Science as an Infrastructure Project in Material Science.

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