Skip to content
Frontiers
Search

Review

Frontiers in Sensors ·

Volume 7 - 2026 | https://doi.org/10.3389/fsens.2026.1774304

Appraisal of organosilane surface modification for probe attachment to biosensor substrates

  • Edmund Chan1
  • Michael Thompson1*corresponding author
  1. Department of Chemistry, University of Toronto, Toronto, ON, Canada
Article metrics0 viewsView details
PDFCiteMetrics

Abstract

In the realm of biosensor technology, organosilane surface chemistry has appeared to be one of the prominent approaches to properly attach biorecognition species onto surfaces of transducer materials. In this regard, the following work briefly elaborates on the fundamentals of the formation of organosilane adlayer, followed by a brief overview of selected examples of important organosilane surface chemistry developed to date.

Keywords

Introduction: organosilane adlayer formation

A key criteria of biosensor development consists in the successful immobilization of biorecognition species (probes) onto surfaces of materials used for device transducer components. Amongst the various probe-attachment approaches to date, organosilane surface chemistry have emerged as a popular option, as they readily form organized bi-functional molecular assemblies (herein termed adlayers) onto hydroxylated surfaces of inorganic or organic substrates (Ulman, 1990; Ulman, 1996). (Prior treatment of such materials to produce hydroxylation may be required.) The bifunctionality of the assembly enables the linking of a probe of choice to the material surface being employed for sensor fabrication. The basic structure of many of such organosilanes is composed of three synthetically customizable components (Figure 1):

Key components of organosilane assemblies used for surface modification (Chan, 2024).
Figure 1. Key components of organosilane assemblies used for surface modification (Chan, 2024).

1. A silyl tail function (often consisting of trialkoxysilyl or trichlorosilyl group) that anchors onto the surface of the material of interest;

2. A distal head function that dictates the overall surface properties of the material, which can be used to attach the probe of interest via an on-surface reaction to create the covalent linkage between the probe and the anchored silane post-assembly.

3. An organic backbone that spaces the head group away from the tail function and reinforces the surface assembly via intermolecular forces.

Whilst there are, in theory, countless possibilities for said organosilane adlayers in terms of overall chemical composition, the availability of head functions that are chemically compatible with the silyl tail function is very limited in reality. In the case of the trichlorosilyl moiety, which is particularly reactive due to the very electrophilic silicon and presence of good leaving groups in the form of chloride, such linkers will not tolerate the presence of nucleophilic head groups (e.g., alcohol, carboxylic acid, amine) that must either be protected during adlayer formation (then deprotected) or introduced post-assembly (Fryxell et al., 1996).

The exact mechanism of adlayer formation is still under debate. However, it has been generally accepted that organosilane adlayers are formed via a multi-stepped mechanism (Silberzan et al., 1991; Schwartz, 2001). The first step of this intricate mechanism begins with the trichlorosilyl moiety or trialkoxysilyl moiety (of said surface linkers) being hydrolyzed to trisilanol anchoring group (Sheikh, 2009) by surface-adsorbed water molecules (Figure 2) (McGovern et al., 1994). The newly formed trisilanol cross-linker subsequently diffuses from the solution bulk to the surface-solution interface, undergoing a reversible adsorption/desorption process involving multiple condensation reactions between said organosilane linker and surface hydroxyl groups to form surface-bound silanols (Figure 2). This ultimately results in formation of islands that nucleate over the surface, expands during a reorganization phase, and aggregates to generate the adlayer, which is further strengthened chemically by covalent cross-linkage between neighboring surface-bound silanols upon additional silanol-to-silanol condensation (Figure 2). The reaction is further driven by intermolecular forces (Van der Waals forces) acting between neighboring organic backbones, providing additional rigidity, order, and stability to the generated adlayer.

Generally-accepted mechanism for organosilane surface adlayer formation (Chan, 2024).
Figure 2. Generally-accepted mechanism for organosilane surface adlayer formation (Chan, 2024).

Various examples of said organosilane adlayers have appeared in the literature over the past decade. The following sections discuss the most prominent of these examples: those incorporating bifunctional propyltrialkoxysilanes and various functionalizable organotrichlorosilanes. A concise list of silane modifiers is summarized in Table 1.

TABLE 1. Summary of selected important organosilanes used for probe surface attachment.

Table summarizing various silane modifiers with columns for silane modifier name, tail function, organic backbone, head function, target probe, probe-anchoring moiety, and pre-activation protocol, highlighting differences in chemical structure and probe compatibility.

Bifunctional propyltrialkoxysilane adlayers

Bifunctional propyltrialkoxysilane linkers have constituted a common foundational approach for immobilizing probe molecules onto hydroxylated inorganic surfaces. These propyltrialkoxysilane surface modifiers consist of a trialkoxysilyl tail function (the alkoxy groups attached to the silicon can be either methoxy or ethoxy) for anchoring onto the surface of the hydroxylated material, and a variety of head functions joined together by a short propyl chain as the organic backbone.

Many of these said propyltrialkoxysilane linkers are readily obtainable commercially. The most prominent of these propyltrialkoxysilane linkers, still heavily used to date, are (3-aminopropyl)trimethoxysilane (APTMS) (Hong et al., 1994) and (3-aminopropyl)triethoxysilane (APTES) (Lu et al., 1993; Sypabekova et al., 2023), both of which terminate with the amino head function (Figure 3). Upon forming the aforementioned adlayers onto the hydroxylated inorganic material of interest, the exposed amino moieties can be used to covalently attach the probe molecule onto the surface via reaction with the carboxylic acid groups (via subsequent treatment with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide (EDC-NHS)) or amino groups (following a pre-activation step with glutaraldehyde) possessed by the probe molecule of interest (Udomsom et al., 2021) (Figure 4). Due to the capacity to target carboxylic acid and amino groups of the probe molecule, the APTMS and APTES surface chemistry has been heavily employed, even to date, for attaching proteins and peptides on a variety of different inorganic materials, among them silicon dioxide (Antoniou et al., 2020), alumina (Nayak et al., 2019), and aluminum nitride (Baur et al., 2005).

Chemical structures of bifunctional propyltrialkoxysilane crosslinkers bearing amino head function (APTMS and APTES), sulfhydryl head function (MPTMS and MPTES), and the epoxide head function (GPTMS and GPTES) (Chan, 2024).
Figure 3. Chemical structures of bifunctional propyltrialkoxysilane crosslinkers bearing amino head function (APTMS and APTES), sulfhydryl head function (MPTMS and MPTES), and the epoxide head function (GPTMS and GPTES) (Chan, 2024).
General Schematic for probe attachment onto inorganic materials modified with silanes (Chan, 2024).
Figure 4. General Schematic for probe attachment onto inorganic materials modified with silanes (Chan, 2024).

Other similar propyltrialkoxysilane surface modifiers have since been developed and made commercially available, among them (3-Mercaptopropyl)trimethoxysilane (MPTMS) (Yee et al., 1991; Bhatia et al., 1992; McGovern and Thompson, 1998) and (3-Mercaptopropyl)triethoxysilane (MPTES) (Mondin et al., 2013). Both linkers bear the sulfhydryl head function (Figure 3), which is useful for reacting with the thiol group from the probe molecule, forming a disulfide bond in the process which covalently immobilizes the probe into the inorganic material of interest (Figure 4). Another series of related trialkoxysilane surface modifiers worthy of mention include (3-Glycidyloxypropyl) trimethoxysilane (GPTMS) (Gabrielli et al., 2014; Trovato et al., 2018) and (3-Glycidyloxypropyl) triethoxysilane (GPTES) (Figure 3) (Guillory et al., 2016). Both linkers terminate in the epoxide head function, a highly reactive functional group whose heavily strained 3-membered ring readily breaks open when a nucleophilic atom (Nu) from the probe molecule undergoes nucleophilic substitution reaction with the less substituted carbon of the epoxide. This process forms a new Nu-C bond which constitutes the covalent linkage between the probe and the inorganic material (Figure 4).

It should be emphasized that the surface chemistry of the aforementioned bifunctional propyltrialkoxysilane linkers is not without drawbacks. The amino-terminating propyl-trialkoxysilane (APTMS and APTES) linker requires the use of pre-activating or coupling agents (EDC-NHS, glutaraldehyde) to facilitate probe attachment, which potentially translates to increased production costs resulting from the use of the said agents to anchor the probe molecules to the surface. In the case of the thiol-bearing variants (MPTMS and MPTES), the exposed sulfhydryl head functions can “cross-react” (i.e., the thiol group of one immobilized linker can form disulfide bonds with that of a neighbouring linker), effectively shutting down the desired sulfhydryl group needed for anchoring thiol-bearing probes. The glycidoxy-bearing counterparts (GPTMS and GPTES), with their reactive epoxide group, can react with a wide range of nucleophilic groups, limiting the scope of the surface chemistry to the immobilization of simple organic molecules. Despite these shortcomings, the said bifunctional trialkoxysilane linkers have remained a popular choice for probe attachment to hydroxylated inorganic surfaces.

Functionalizable alkyltrichlorosilane surface modifiers

While commercially available bifunctional propyltrialkoxysilane adlayers have remained a popular approach to simple probe attachment to date, there have been recent research interests dedicated towards novel functionalizable orangotrichlorosilane as an alternative approach for probe attachment. These linkers contain the more reactive trichlorosilyl tail function in place of the trialkoxysilyl moiety (to anchor onto the said hydroxylated surface) and the distal head group, connected by an organic backbone. These trichlorosilane modifiers are typically synthesized by preparing analogous precursor molecules bearing the terminal alkene as the tail function. These terminal alkene molecules are subsequently treated with trichlorosilane (HSiCl3) and chloroplatinic acid hexahydrate (H2PtCl6•6H2O), both of which, in tandem, convert the terminal alkene moiety into the Cl3Si- anchoring function via the classical catalytic hydrosilylation reaction (Figure 5) (Speier et al., 1957; Blaszykowski et al., 2012).

General schematic for synthesis of trichlorosilane surface modifier (Chan, 2024).
Figure 5. General schematic for synthesis of trichlorosilane surface modifier (Chan, 2024).

Various examples of these functionalizable trichlorosilane linkers have appeared in the literature. The most prominent examples of these, first developed in our laboratory, incorporated long alkyl chain as organic backbones, along with pentafluorophenyl ester (PFP) and benzenethiosulfonate (BTS) as modifiable head functions (Figure 6) (Blaszykowski et al., 2012). The PFP moiety is selected for its potent reactivity with primary amine residues to form strong amide bonds, whereas the BTS head function is chosen for its regioselectivity with sulfhydryl groups (thiols) to selectively form disulfide bonds (Blaszykowski et al., 2012; Zefirov et al., 1993).

Functionalizable organotrichlorosilane surface modifiers developed in house bearing PFP and BTS head function and alkyl chain backbone (Blaszykowski et al., 2012).
Figure 6. Functionalizable organotrichlorosilane surface modifiers developed in house bearing PFP and BTS head function and alkyl chain backbone (Blaszykowski et al., 2012).

The PFP-based alkyltrichlorosilane linker has since been used to modify AT-cut quartz surfaces, which was subsequently used to immobilize various amine-bearing probes. In one reported example, Nα,Nα-Bis(carboxymethyl)-L-lysine (NTAL) was anchored onto PFP-modified quartz surfaces in order to functionalize said surfaces with nitrilotriacetic acid (NTA) moiety, which was subsequently used to form nickel (II) coordinate complexes with Polyhistidine-tagged (His-tagged) heat shock protein 10 (HSP-10) (Figure 7) (Chen et al., 2016). The PFP-based silane surface chemistry, with its reactivity to amine moieties, completely avoided the use of activating agent (such as glutaraldehyde) for anchoring amine-bearing probes, rendering it far superior to the traditional APTMS and APTES surface chemistry.

Functionalization of PFP modified quartz with Nα,Nα-Bis(carboxymethyl)-L-lysine and subsequent nickel (II) complex formation between on-surface NTA and His-tagged HSP-10 (Chen et al., 2016).
Figure 7. Functionalization of PFP modified quartz with Nα,Nα-Bis(carboxymethyl)-L-lysine and subsequent nickel (II) complex formation between on-surface NTA and His-tagged HSP-10 (Chen et al., 2016).

In a separate example, the BTS-based alkyltrichlorosilane adlayers have been imposed into aluminum nitride (AlN) thin films, an alternative piezoelectric substrate being considered for future incorporation into acoustic wave biosensor (Chan et al., 2013). As a demonstration of the reactivity of the ideally exposed BTS head function to sulfhydryl groups, the BTS-modified AlN films were subsequently treated with thiolated biotin groups as a proof-of-concept (Figure 8) (Chan et al., 2013). The BTS silane surface chemistry exhibits selectivity for only the thiol groups from the probe molecules, making it a much more reliable approach than the more documented MPTMS and MPTES approaches, as the surface-immobilized BTS head groups do not cross-react.

Surface modification of aluminum nitride thin films with BTS alkyltrichlorosilane adlayers and subsequent probe attachment with thiolated biotin probes (Chan et al., 2013).
Figure 8. Surface modification of aluminum nitride thin films with BTS alkyltrichlorosilane adlayers and subsequent probe attachment with thiolated biotin probes (Chan et al., 2013).

Ethylene glycol (EG) based trichlorosilane surface modifiers

Alongstide the development of said PFP-based and BTS-based alkyltrichlorosilane surface chemistry, our laboratory has also recently been interested in incorporating the ethylene glycol (EG) moiety as an alternative organic backbone in our silane surface modifier design (Sheikh et al., 2010). Our interest in the EG moiety has been largely inspired by its well-documented ability to reduce adsorption of proteins and cells from biological fluids onto various material surfaces. In the context of biosensor technology, this particular property of EG is especially important for combating the ever existing issue of non-specific adsorption (NSA) (or fouling), which, otherwise, interferes with device selectivity and sensitivity of said biosensors. Our first examples of EG-based trichlorosilane linkers developed in-house included the spacer molecule MEG-OH (Figure 9), which incorporated one unit of EG in the backbone and terminated with a hydroxyl head function. Due to the otherwise incompatibility of the hydroxyl head function and the trichlorosilyl tail function for the prospective linker, the surface MEG-OH adlayer was typically achieved by synthesizing the precursor trichlorosilane linker bearing the trifluoroacetyl ester head function (MEG-TFA), and then deprotecting the trifluoroacetyl ester post-assembly (which generated the exposed hydroxyl head functions, forming the MEG-OH adlayer). In our laboratory, MEG-TFA and MEG-OH adlayers were used to modify AT-cut quartz, which were incorporated as a transducing agent in acoustic wave biosensor experiments. Through the said experiments, it was found that the single EG moiety in the silane backbone of MEG-OH compared to other modifiers resulted in a dramatic reduction in fouling from serum (Figure 9) (Sheikh et al., 2012), a result that is clearly associated with the specific molecular structure imposed at the quartz surface.

Structures of MEG-TFA and MEG-OMe organosilane linkers (top), surface modifications of quartz with various organosilane surface modifiers (middle), and frequency shift studies of untreated (bare) and various organosilane-modified quartz on exposure to undiluted goat serum using an acoustic wave biosensor (bottom) (Sheikh et al., 2012).
Figure 9. Structures of MEG-TFA and MEG-OMe organosilane linkers (top), surface modifications of quartz with various organosilane surface modifiers (middle), and frequency shift studies of untreated (bare) and various organosilane-modified quartz on exposure to undiluted goat serum using an acoustic wave biosensor (bottom) (Sheikh et al., 2012).

Further studies involving molecular dynamics calculations (Sheikh et al., 2015) and neutron reflectometry experiments (Pawlowska et al., 2014) conducted in our laboratory suggested that the incorporated EG backbone in MEG-OH facilitates the formation of a distinct interfacial water barrier, which constitutes an energy cost to perturbation, and, in turn, suppresses the protein dehydration process during protein adsorption onto inorganic surfaces.

Alongside the development of MEG-TFA and MEG-OH silanes used as spacer molecules, our laboratory has also developed various other EG-based trichlorosilane geared towards subsequent probe attachment, with particular attention geared towards tuning the number of EG units incorporated into the organic backbone in an attempt to enhance the effect of reduction of NSA (Sheikh et al., 2010). One such linker developed in-house is OEG-TTTA, which incorporates the replaceable, 2,2,2-trifluoroethyl ester (TFE) head group (Figure 10). The selection of the TFE group is chosen due to its selectivity towards reaction with primary amines (Kohler et al., 2004; Veiseh et al., 2005; Latham and Williams, 2006; Biesta et al., 2012). Another of these EG-based silane surface modifiers developed in-house consisted of OEG-TUBTS (Figure 10), which possesses the thiol-selective BTS head group. Both of these molecules have been employed successfully to modify AT-quartz in preparation for subsequent probe attachment whilst preserving the antifouling property. In one reported example, the OEG-TTTA linker was used in tandem with the said MEG-OH spacer for the covalent immobilization of polymyxin B for the detection of lipopolysaccharide (LPS) (Thompson et al., 2015).

Selected EG-based trichlorosilane surface modifiers bearing TFE (OEG-TTTA) and BTS (OEG-TUBTS) replaceable head functions (Sheikh et al., 2010).
Figure 10. Selected EG-based trichlorosilane surface modifiers bearing TFE (OEG-TTTA) and BTS (OEG-TUBTS) replaceable head functions (Sheikh et al., 2010).

Further experiments were conducted to better understand the correlation between number of EG moieties and NSA reduction. In this context, TFA-bearing trichlorosilanes of varying number of EG moieties (7-OEG-TFA, 10-OEG-TFA, and 13-OEG-TFA) were synthesized (Figure 11) and used to modify AT-cut quartz, with the TFA head functions being deprotected post-assembly to expose the distal OH head functions (forming adlayers of 7-OEG, 10-OEG, 13-OEG).

Structures of 7-OEG-TFA, 10-OEG-TFA, and 13-OEG-TFA trichlorosilane linkers (Sheng et al., 2021).
Figure 11. Structures of 7-OEG-TFA, 10-OEG-TFA, and 13-OEG-TFA trichlorosilane linkers (Sheng et al., 2021).

Through acoustic wave sensors experiments using said modified quartz, it was found upon exposure to undiluted goat serum, the 7-OEG adlayers exhibited much lower fouling relative to the adlayers consisting of the longer molecules (i.e. 10–OEG and 13–OEG), despite the latter containing higher numbers of EG groups (Figure 12) (Sheng et al., 2021). This result strongly suggests that the silane adlayers bearing shorter chain length (lower number of EG moieties) possess enhanced resistance to NSA (Sheng et al., 2021). This is very likely associated with the fact that the lower packing density formed by shorter molecules allows better water penetration to form the aforementioned interstitial zone. As the chain length (number of EG moieties) increases, the adlayer becomes more densely packed thus obviating such water penetration.

Functionalization of quartz with 7–OEG–TFA and 13–OEG–TFA and subsequent cleavages of the protecting TFA group (top) (10–OEG–TFA surface attachment and cleavage, though not shown, was carried out on quartz in a similar fashion); Frequency shift study of untreated (cleaned) and organosilane-modified quartz (7-OEG, 10-OEG, 13-OEG) on exposure to undiluted goat serum using an ultra-high frequency acoustic wave biosensor (bottom) (Sheng et al., 2021).
Figure 12. Functionalization of quartz with 7–OEG–TFA and 13–OEG–TFA and subsequent cleavages of the protecting TFA group (top) (10–OEG–TFA surface attachment and cleavage, though not shown, was carried out on quartz in a similar fashion); Frequency shift study of untreated (cleaned) and organosilane-modified quartz (7-OEG, 10-OEG, 13-OEG) on exposure to undiluted goat serum using an ultra-high frequency acoustic wave biosensor (bottom) (Sheng et al., 2021).

The MEG-Cl surface modifier

Finally, we have researched the sister molecule to MEG-OH, 3-(3-(trichlorosilyl-propyloxy)propanoyl chloride (MEG-Cl) (Figure 13) (De La Franier et al., 2017; Spagnolo et al., 2020). This particular surface modifier functions both as a linker for subsequent probe attachment as well as a general spacer molecule aimed to reduce adsorption on surfaces in a similar manner to aforementioned the MEG-OH adlayer. The MEG-Cl surface chemistry has since be used to modify hydroxylated materials for various purposes, among them the attachment of Ni-NTA for the binding of recombinant proteins (De La Franier et al., 2017), as well as to reduce fouling by serum and milk samples. In one particular study, it was shown, through acoustic wave sensors experiments incorporating MEG-Cl modified quartz substrates, that the MEG-Cl coated surfaces possessed a large degree of anti-fouling that were comparable to previously studied MEG-OH-modified surfaces (Spagnolo et al., 2020). With respect to practical implementation, the surface chemistry has been employed in conjunction with an aptamer-based sensor specific to Escherichia coli (E. coli) (Spagnolo et al., 2022). In this context, the aptamer is being covalently tethered to the quartz surface (of the acoustic wave sensor setup) through the anti-fouling linker, MEG-Cl. The sensor is capable of the selective measurement of E coli in phosphate buffered saline and in cow’s milk samples down to limits of detection of 35 and 8 CFU/mL, respectively, which is well below the safe limits for commercial milk products.

Structure of the MEG-Cl surface linker (De La Franier et al., 2017).
Figure 13. Structure of the MEG-Cl surface linker (De La Franier et al., 2017).

Final remarks

Organosilane surface chemistry continues to be a popular method for attachment of appropriate probe molecules to various materials employed for biosensor fabrication. While the examples covered in the present work focused on inorganic substrates, there have been cases involving organic materials, e.g., polymers. Regardless, successful implementation of organosilane surface chemistry for probe requires the following crieria to be considered:

  • The underlying transducer material is required to possess a large coverage of surface hydroxyl groups in order to facilitate the multiple condensation steps (upon exposure of surface to organosilanes) during the organosilane adlayer formation. While many metallic substrates innately bear these surface hydroxyl groups (or can be treated easily to possess said surface hydroxyl groups), it is rather challenging to install said hydroxyl groups on polymers and other non-metallic materials. In such cases, special surface oxidation techniques, such as oxygen plasma treatment, may be implemented to functionalize such materials with the necessary hydroxyl groups.
  • A key issue for probe attachment lies in the necessity to achieve “ideal’ lateral spacing of the probe on the device being fabricated, which, in the context of organosilanes, is typically achieved by careful optimization of the ratio of the spacer silane molecule versus the probe-anchoring silane linker used to functionalize the transducer material. While having a higher abundance of surface-immobilized probes is highly desirable for for sensitivity purposes, the accompanying close proximity effects between neighbouring probes can potentially lead to a compromising of bio-recognition capability. Indeed, striking an ideal balance between sensitivity and spacing of probes is a challenging aspect of this organosilane surface chemistry.
  • As summarized above, an important structural element of silane linking species and spacer molecules is the incorporation of anti-fouling chemistry in both moieties. This is mandatory if it is envisaged that assay of low concentrations analyses in matrices such as blood and serum is involved. In our research, we have shown that short backbone chains with a EG functionality represent the best approach.
  • One issue that is rarely addressed in the world of biosensor technology is the orientation of the attached probe on the particular transducer being employed. The reality is that the linking process to attach probe molecules to surface modifiers such as silanes can lead to either “blocking” of the bio-recognition site or a compromise of the biological probe structure. To address these issues, one approach is the development of surface modifiers that incorporate novel head groups designed to specifically target important biological motifs found in the probe molecules. In the context of protein (and peptide-based) probes, one interesting idea consists in developing linkers with head functions that can covalently target important peptide tags that are terminally-generated in proteins/peptides during their expression. This can be achieved via immobilizing His-tagged proteins by targeting the His-tag motif. Such surface chemistry offers the potential to immobilize, virtually, any protein or important peptide of interest onto the inorganic material of interest while providing better control over the orientation of the protein or peptide.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Footnotes

Edited by: Rosaria Anna Picca, University of Bari Aldo Moro, Italy

Reviewed by: Luisa Pilan, Politehnica University of Bucharest, Romania

Kulvinder Singh, DAV College, India

Footnotes

APTES, (3-aminopropyl)triethoxysilane; APTMS, (3-aminopropyl)trimethoxysilane; BTS, Benzenethiosulfonate; Cl3Si-, Trichlorosilyl; EG, Ethylene glycol; E. coli, Escherichia coli; GPTES, (3-Glycidyloxypropyl)triethoxysilane; GPTMS, (3-Glycidyloxypropyl)trimethoxysilane; HSP-10, Heat shock protein 10; His-tag, Polyhistidine peptide; MPTES, (3-Mercaptopropyl)triethoxysilane; MPTMS, (3-Mercaptopropyl)trimethoxysilane; MEG-Cl, (3-(3-(trichlorosilylpropyloxy)propanoyl chloride; MEG-TFA, 2-(3-trichlorosilylpropyloxy)-ethyl trifluoroacetate; OEG-TTTA 5.3-(2-(2-(3-trichlorosilylpropyloxy)-ethoxy)-ethoxy)-propanoic acid 2,2,2-, trifluoroethyl ester; OEG-TUBTS, (2–(3–trichlorosilyl–propyloxy)–ethoxy)–ethoxy)–ethyl)benzenethiosulfonate; MEG-OMe, Ethylene glycol 3-trichlorosilylpropyl methyl ether; 7-OEG-TFA, Trifluoroaceticacid 2–(3–trichlorosilyl–propyloxy)–ethyl ester; 10-OEG-TFA, Trifluoroacetic acid 2–(2–(3–trichlorosilyl–propyloxy)–ethoxy)–ethyl ester; 13-OEG-TFA Trifluoroacetic acid 2–(2–(2–(3–trichlorosilyl-propyloxy)–ethoxy)—ethoxy)–ethyl, ester; PFP, Pentafluorophenyl ester; TFA, Trifluoroacetic acid; TUBTS, S–(11–trichlorosilylundecanyl)benzenethiosulfonate.

Statements

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declared that financial support was not received for this work and/or its publication.

Author contributions

EC: Formal Analysis, Writing – original draft, Writing – review and editing, Investigation. MT: Conceptualization, Formal Analysis, Project administration, Supervision, Writing – original draft, Writing – review and editing.

References

  1. Antoniou M., Tsounidi D., Petrou P. S., Beltsios K. G., Kakabakos S. E. (2020). Functionalization of silicon dioxide and silicon nitride surfaces with aminosilanes for optical biosensing applications. Med. Devices. Sens. 3 (5), e10072. doi:10.1002/mds3.10072
  2. Baur B., Steinhoff G., Hernando J., Purrucker O., Tanaka M., Nickel B. (2005). Chemical functionalization of GaN and AlN surfaces. Appl. Phys. Lett. 87 (26), 263901. doi:10.1063/1.2150280
  3. Bhatia S. K., Hickman J. J., Ligler F. S. (1992). New approach to producing patterned biomolecular assemblies. J. Am. Chem. Soc. 114 (2), 981 – 986. doi:10.1021/ja00037a077
  4. Biesta W., Van Lagen B., Gevaert V. S., Marcelis A. T. M., Paulusse J. M. J., Nielen M. W. F. (2012). Preparation, characterization, and surface modification of trifluoroethyl ester-terminated silicon nanoparticles. Chem. Mater. 24 (22), 4311 – 4318. doi:10.1021/cm302060f
  5. Blaszykowski C., Sheikh S., Benvenuto P., Thompson M. (2012). New functionalizable alkyltrichlorosilane surface modifiers for biosensor and biomedical applications. Langmuir 28 (5), 2318 – 2322. doi:10.1021/la2042839
  6. Chan E. (2024). Novel silane surface chemistry for covalent immobilization with n-protected histidine: towards improved functionalization of hydroxylated materials with his-tagged biomolecules. [dissertation]. Toronto, ON: University of Toronto (Accessed May 20, 2026).
  7. Chan E., Jackson N., Mathewson A., Galvin P., Alamin Dow A. B., Kherani N. P. (2013). Surface modification of piezoelectric aluminum nitride with functionalizable organosilane adlayers. Appl. Surf. Sci. 282, 709 – 713. doi:10.1016/j.apsusc.2013.06.039
  8. Chen J. B., Neves M. A. D., Thompson M. (2016). Biosensor surface attachment of the ovarian cancer biomarker HSP10 via his-tag modification. Sens. Biosensing Res. 11, 107 – 112. doi:10.1016/j.sbsr.2016.10.006
  9. De La Franier B., Jankowski A., Thompson M. (2017). Functionalizable self-assembled trichlorosilyl-based monolayer for application in biosensor technology. Appl. Surf. Sci. 414, 435 – 441. doi:10.1016/j.apsusc.2017.04.111
  10. Fryxell G. E., Rieke P. C., Wood L. L., Engelhard M. H., Williford R. E., Graff G. L. (1996). Nucleophilic displacements in mixed self-assembled monolayers. Langmuir 12 (21), 5064 – 5075. doi:10.1021/la9506842
  11. Gabrielli L., Connell L., Russo L., Jiménez-Barbero J., Nicotra F., Cipolla L. (2014). Exploring GPTMS reactivity against simple nucleophiles: chemistry beyond hybrid materials fabrication. RSC Adv. 4 (4), 1841 – 1848. doi:10.1039/c3ra44748k
  12. Guillory X., Tessier A., Gratien G. O., Weiss P., Colliec-Jouault S., Dubreuil D. (2016). Glycidyl alkoxysilane reactivities towards simple nucleophiles in organic media for improved molecular structure definition in hybrid materials. RSC Adv. 6 (78), 74087 – 74099. doi:10.1039/c6ra01658h
  13. Hong H.-G., Jiang M., Sligar S. G., Bohn P. W. (1994). Cysteine-specific surface tethering of genetically engineered cytochromes for fabrication of Metalloprotein nanostructures. Langmuir 10, 153 – 158. doi:10.1021/la00013a023
  14. Kohler N., Fryxell G. E., Zhang M. (2004). A bifunctional Poly(Ethylene glycol) silane immobilized on metallic oxide-based nanoparticles for conjugation with cell agents. J. Am. Chem. Soc. 126 (23), 7206 – 7211. doi:10.1021/ja049195r
  15. Latham A. H., Williams M. E. (2006). Versatile routes toward functional, water-soluble nanoparticles via Trifluoroethylester-PEG-Thiol ligands. Langmuir 22 (9), 4319 – 4326. doi:10.1021/la053523z
  16. Lu B., Wu C. R., Yang W. Y., Wei Y. (1993). The binding of bifunctional reagents to silanized silicon surfaces studied by angle-dependent X-Ray Photoelectron spectroscopy. Appl. Surf. Sci. 72 (2), 125 – 132. doi:10.1016/0169-4332(93)90002-s
  17. McGovern M. E., Thompson M. (1998). Self-Assembled silanes and the Thiol functionalization of surfaces. Anal. Commun. 35, 391 – 393. doi:10.1039/a807021k
  18. McGovern M. E., Kallury K. M. R., Thompson M. (1994). Role of solvent on the silanization of glass with octadecyltrichlorosilane. Langmuir 10 (17), 3607 – 3614. doi:10.1021/la00022a038
  19. Mondin G., Lohe M. R., Wisser F. M., Grothe J., Mohamed-Noriega N., Leifert A. (2013). Electroless copper deposition on (3-Mercaptopropyl)Triethoxysilane-Coated silica and Alumina nanoparticles. Electrochim. Acta. 114, 521 – 526. doi:10.1016/j.electacta.2013.10.055
  20. Nayak N., Huertas R., Crespo J. G., Portugal C. A. M. (2019). Surface modification of Alumina Monolithic columns with 3-Aminopropyltetraethoxysilane (APTES) for protein attachment. Sep. Purif. Technol. 229, 115674. doi:10.1016/j.seppur.2019.115674
  21. Pawlowska N. M., Fritzsche H., Blaszykowski C., Sheikh S., Vezvaie M., Thompson M. (2014). Probing the hydration of ultrathin antifouling organosilane adlayers using neutron reflectometry. Langmuir 30 (5), 1199 – 1203. doi:10.1021/la4038233
  22. Schwartz D. K. (2001). Mechanisms and kinetics of self-assembled monolayer Formation. Annu. Rev. Phys. Chem. 52 (1), 107 – 137. doi:10.1146/annurev.physchem.52.1.107
  23. Sheikh S. (2009). Selective biochemical interactions studied by an ultra high frequency acoustic wave device. [Master’s Thesis]. Toronto, ON: University of Toronto. 4–5 (Accessed April 7, 2026).
  24. Sheikh S., Sheng J. C.-C., Blaszykowski C., Thompson M. (2010). New oligoethylene glycol linkers for the surface modification of an ultra-high frequency Acoustic wave biosensor. Chem. Sci. 1 (2), 271 – 275. doi:10.1039/c0sc00158a
  25. Sheikh S., Yang D. Y., Blaszykowski C., Thompson M. (2012). Single ether group in a glycol-based ultra-thin layer prevents surface fouling from undiluted serum. Chem. Commun. 48, 1305 – 1307. doi:10.1039/c2cc15692j
  26. Sheikh S., Blaszykowski C., Nolan R., Thompson D., Thompson M. (2015). On the hydration of subnanometric antifouling organosilane adlayers: a molecular dynamics simulation. J. Colloid Interface Sci. 437, 197 – 204. doi:10.1016/j.jcis.2014.09.025
  27. Sheng J. C., De La Franier B., Thompson M. (2021). Assembling surface linker chemistry with minimization of non-specific adsorption on biosensor. Materials 14, 472. doi:10.3390/ma14020472
  28. Silberzan P., Léger L., Ausserré D., Benattar J. J. (1991). Silanation of Silica surfaces. A new method of constructing pure or mixed monolayers. Langmuir 7 (8), 1647 – 1651. doi:10.1021/la00056a017
  29. Spagnolo S., De La Franier B., Hianik T., Thompson M. (2020). Surface probe linker with tandem anti-fouling properties for application in biosensor technology. Biosensors 10, 20. doi:10.3390/bios10030020
  30. Spagnolo S., De La Franier B., Davoudian K., Hianik T., Thompson M. (2022). Detection of E. coli bacteria in milk by an Acoustic wave aptasensor with an anti-fouling coating. Sensors 22 (5), 1853. doi:10.3390/s22051853
  31. Speier J. L., Webster J. A., Barnes G. H. (1957). The addition of silicon hydrides to olefinic double bonds. Part II. The Use of Group VIII metal catalysts. J. Am. Chem. Soc. 79, 974 – 979. doi:10.1021/ja01561a054
  32. Sypabekova M., Hagemann A., Rho D., Kim S. (2023). Review: 3-Aminopropyltriethoxysilane (APTES) deposition methods on oxide surfaces in solution and vapor phases for biosensing applications. Biosens. (Basel) 13 (1), 36. doi:10.3390/bios13010036
  33. Thompson M., Blaszykowski C., Sheikh S., Romaschin A. (2015). A true Theranostic approach to medicine: towards tandem sensor detection and removal of Endotoxin in blood. Biosens. Bioelectron. 67, 3 – 10. doi:10.1016/j.bios.2014.07.008
  34. Trovato V., Colleoni C., Castellano A., Plutino M. R. (2018). The key role of 3-Glycidoxypropyltrimethoxysilane sol–gel precursor in the development of wearable sensors for health monitoring. J. Solgel. Sci. Technol. 87, 27 – 40. doi:10.1007/s10971-018-4695-x
  35. Udomsom S., Mankong U., Paengnakorn P., Theera-Umpon N. (2021). Novel rapid protein coating technique for silicon photonic biosensor to improve surface morphology and increase bioreceptor density. Coatings 11 (5), 595. doi:10.3390/coatings11050595
  36. Ulman A. (1990). Self-Assembled monolayers of alkyltrichlorosilanes: building blocks for future organic materials. Adv. Mater. 2 (12), 573 – 582. doi:10.1002/adma.19900021203
  37. Ulman A. (1996). Formation and structure of self-assembled monolayers. Chem. Rev. 96 (4), 1533 – 1554. doi:10.1021/cr9502357
  38. Veiseh O., Sun C., Gunn J., Kohler N., Gabikian P., Lee D. (2005). Optical and MRI multifunctional nanoprobe for targeting gliomas. Nano Lett. 5 (6), 1003 – 1008. doi:10.1021/nl0502569
  39. Yee J. K., Parry D. B., Caldwell K. D., Harris J. M. (1991). Modification of quartz surfaces via Thiol-Disulfide interchange. Langmuir 7, 307 – 313. doi:10.1021/la00050a018
  40. Zefirov N. S., Zyk N. V., Beloglazkina E. K., Kutateladze A. G. (1993). Thiosulfonates: synthesis, reactions and practical applications. Sulfur Rep. 14 (1), 223 – 240. doi:10.1080/01961779308055018

Citation

Chan, E. & Thompson, M. (2026). Appraisal of organosilane surface modification for probe attachment to biosensor substrates. Frontiers in Sensors, Volume 7. https://doi.org/
Received
Accepted
Published
Volume
7 - 2026

Copyright

Copyright © 2026 Chan and Thompson.

License: https://creativecommons.org/licenses/by/4.0/

*Correspondence: Michael Thompson

Article metrics

Views
0
Downloads
0
Citations
0
Shares
0

Related articles

ReviewAdvances and applications of wearable electrochemical sensors in personalised medicine and precision agriculture: a systematic reviewVaibhav Sharma, Anuj Sharma, Raj Shukla, Mahipal Singh Sankhla, Garima Awasthi, Amanpreet Singh, Manpreet Kaur, Diksha Pathania, Sheifali Gupta, Kumud Kant Awasthi, Harsh SableOriginal ResearchPathogenic bacteria sensing with tellurium dioxide/cadmium gallium sulfide-assisted surface plasmonic resonance refractive index sensor: a machine learning approachRajanidevi Merigala, Sandeep Boddu, Yesudasu Vasimalla, Mallellu Sai Prashanth, Saleh Chebaane, Norah A. M. Alsaif, Sana Ben Khalifa, Bhishma KarkiOriginal ResearchA centralized mapping architecture for Automated Streetlight Fault Detection via Wireless Sensor Mesh NetworksSwarnajit Bhattacharya, Biswajit Mandal, Banshidhari Samanta