The original commercial AFM-IR instruments required most samples to be thicker than 50 nm to achieve sufficient sensitivity. Sensitivity improvements were achieved using specialized cantilever probes with an internal resonator and by wavelet based signal processing techniques. Sensitivity was further improved by Lu et al. by using quantum cascade laser (QCL) sources. The high repetition rate of the QCL allows absorbed infrared light to continuously excite the AFM tip at a "contact resonance" of the AFM cantilever. This resonance-enhanced AFM-IR, in combination with electric field enhancement from metallic tips and substrates led to the demonstration of AFM-IR spectroscopy and compositional imaging of films as thin as single self-assembled monolayers. AFM-IR has also been integrated with other sources including a picosecond OPO offering a tuning range 1.55 μm to 16 μm (from 6450 cm to 625 cm).
In its initial development, with samples deposited on transparent prisms and using OPO laser sources, the sensitivity of AFM-IR was limited to a minimal thickness of the sample of circa 50-100 nm as mentioned above. The advent of quantum cascade lasers (QCL) and the use of the electromagnetic field enhancement between metallic probes and substrates have improved the sensitivity and spatial resolution of AFM-IR down to the measurement of large (>0.3 μm) and flat (~2–10 nm) self-assembled monolayers, where still hundreds of molecules are present. Ruggeri et al. have recently developed off-resonance, low power and short pulse AFM-IR (ORS-nanoIR) to prove the acquisition of infrared absorption spectra and chemical maps at the single molecule level, in the case of macromolecular assemblies and large protein molecules with a spatial resolution of ca. 10 nm.