Tuning forks as tip–sample distance detectors are a promising and versatile alternative to conventional cantilevers with optical beam deflection in noncontact atomic force microscopy (AFM). Both theory and experiments are presented to make a comparison between conventional and tuning-fork-based AFM. Measurements made on a Si(111) sample show that both techniques are capable of detecting monatomic steps. The measured step height of 0.33 nm is in agreement with the accepted value of 0.314 nm. According to a simple model, interaction forces of 30 pN are obtained for the tuning-fork-based setup, indicating that, at the proper experimental conditions, the sensitivity of such an instrument is competitive to conventional lever-based AFM.
We present a study of the dynamic behavior of tuning forks and the application of tuning fork based shear force microscopy on soft samples in liquid. A shift in resonance frequency and a recovery of the tip vibration amplitude have been observed upon immersion into liquid. Conservation of the vibration mode is confirmed by both direct stroboscopic observation and by detection of the tip vibration amplitude of the tuning fork. Thanks to the partial recovery of the Q factor upon complete immersion into liquid, it is possible to obtain high-resolution images on soft samples in liquid. This opens a new domain of applications for tuning fork based near-field scanning optical microscopes.
ObjectivesIn rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA.MethodsIn 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference.ResultsAt the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005.ConclusionsIn this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.
Throughout the years, fluorescence microscopy has proven to be an extremely versatile tool for cell biologists to study live cells. Its high sensitivity and non-invasiveness, together with the ever-growing spectrum of sophisticated fluorescent indicators, ensure that it will continue to have a prominent role in the future. A drawback of light microscopy is the fundamental limit of the attainable spatial resolution – ∼250 nm – dictated by the laws of diffraction. The challenge to break this diffraction limit has led to the development of several novel imaging techniques. One of them, near-field scanning optical microscopy (NSOM), allows fluorescence imaging at a resolution of only a few tens of nanometers and, because of the extremely small near-field excitation volume, reduces background fluorescence from the cytoplasm to the extent that single-molecule detection sensitivity becomes within reach. NSOM allows detection of individual fluorescent proteins as part of multimolecular complexes on the surface of fixed cells, and similar results should be achievable under physiological conditions in the near future.
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