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Microcantilever sensor technology has been steadily growing for the last 15 years. While we have gained a great amount of knowledge in microcantilever bending due to surface stress changes, which is a unique property of microcantilever sensors, we are still in the early stages of understanding the fundamental surface chemistries of surface-stress-based microcantilever sensors. In general, increasing surface stress, which is caused by interactions on the microcantilever surfaces, would improve the S/N ratio and subsequently the sensitivity and reliability of microcantilever sensors. In this review, we will summarize (A) the conditions under which a large surface stress can readily be attained and (B) the strategies to increase surface stress in case a large surface stress cannot readily be reached. We will also discuss our perspectives on microcantilever sensors based on surface stress changes. 10.1021/ac901955d

We report a novel enzyme-based microcantilever sensor by using layer-by-layer nanoassembly modification. A glucose oxidase (GOx) functionalized microcantilever underwent bending when it was exposed to glucose solutions. The magnitudes of bending were proportional to the concentrations of glucose. The cantilever bending was specific toward glucose, but not to other sugars such as mannose, fructose, or galactose. The flow rate effect on the cantilever bending response is also discussed. The bending mechanism was investigated, and the kinetic and thermodynamic analysis and experimental results showed that the conformational change of GOx and gluconic formation were the origin of cantilever deflection.

Femtomolar concentrations of hydrogen fluoride, a decomposition component of nerve agents, were detected using a Si[O.sub.2] microcantilever. The microcantilever underwent bending due to the reaction of HF with Si[O.sub.2]. The microcantilever deflection increased as the concentration of HF increased. Other acids, such as HCl, had no effect on the deflection of the cantilever. The mechanism of reaction-induced bending and the correlation of microcantilever deflection with the HF concentration are discussed. The deflection in response to HF of a commercially available silicon cantilever was also studied, and its response was compared with that of the Si[O.sub.2] cantilever. Much less bending amplitude and sensitivity were observed for the silicon cantilever.

Hydrogels containing various mounts of tetraalkylammonium salts were used to modify microcantilevers for measurements of the concentration of Cr[O.sub.4.sup.2-] in aqueous solutions. These microcantilevers undergo bending deflection upon exposure to solutions containing various Cr[O.sub.4.sup.2-] concentrations as a result of swelling or shrinking of the hydrogels. The microcantilever deflection as a function of the concentration of Cr[O.sub.4.sup.2-] ions is nearly linear in most concentration ranges. It was found that a concentration of [10.sup.-11] M Cr[O.sub.4.sup.2-] can be detected using this technology in a fluid cell. Other ions, such as [Br.sup.-], HP[O.sub.4.sup.2-], and N[O.sub.3.sup.-], have minimal effect on the deflection of this cantilever. The anions S[O.sub.4.sup.2-] and C[O.sub.3.sup.2-] could interfere with the Cr[O.sub.4.sup.2-] detection, but only at high concentrations (> [10.sup.-5] M). Such hydrogel-coated microcantilevers could potentially be used to prepare microcantilever-based chemical and biological sensors when molecular recognition agents are immobilized in the hydrogel.

Trace amounts of [Hg.sup.2+] are detected by using a microcantilever coated with gold. The microcantilever undergoes bending due to accumulation of [Hg.sup.2+] on the gold surface. It is found that a concentration of [10.sup.-11] M [Hg.sup.2+] can be detected using this technology. Other cations, such as [K.sup.+], [Na.sup.+], [Pb.sup.2+], [Zn.sup.2+], [Ni.sup.2+], [Cd.sup.2+], [Cu.sup.2+], and [Ca.sup.2+] have little or no effect on the deflection of the cantilever. The selectivity of the [Hg.sup.2+] sensor could be improved by coating the gold surface of microcantilever with a self-assembled monolayer of a long-chain thiol compound.

Characterization of single-nucleotide polymorphisms is a major focus of current genomics research. We demonstrate the discrimination of DNA mismatches using an elegantly simple microcantilever-based optical deflection assay, without the need for external labeling. Gold-coated silicon AFM cantilevers were functionalized with thiolated 20- or 25-mer probe DNA oligonucleotides and exposed to target oligonucleotides of varying sequence in static and flow conditions. Hybridization of 10-mer complementary target oligonucleotides resulted in net positive deflection, while hybridization with targets containing one or two internal mismatches resulted in net negative deflection. Mismatched targets produced a stable and measurable signal when only a four-base pair stretch was complementary to the probe sequence. This technique is readily adaptable to a high-throughput array format and provides a distinct positive/negative signal for easy interpretation of oligonucleotide hybridization.

Microcantilevers modified with a self-assembled monolayer respond sensitively to specific ion concentrations. Here, we report the detection of trace amounts of [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] using microcantilevers modified with a self-assembled monolayer of triethyl-12-mercaptododecylammonium bromide. The self-assembled monolayer was prepared on a silicon microcantilever coated with a thin layer of gold on one side. The microcantilever undergoes bending due to sorption of [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] ions on the monolayer-modified side. It was found that a concentration of [10.sup.-9] M [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] call be detected using this technology in a flow cell. Other anions, such as [Cl.sup.-], [Br.sup.-], [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], and [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], have minimal effect on the deflection of this cantilever. The mechanics of the bending and the chemistry of cantilever modification are discussed.

The emission properties of a supramolecular fluorescent probe, mimicking the function of a logic gate, are reported.