Visualization of biomedical samples in their native environments at the microscopic scale is crucial for studying fundamental principles and discovering biomedical systems with complex interaction. The study of dynamic biological processes requires a microscope system with multiple modalities, high spatial/temporal resolution, large imaging ranges, versatile imaging environments and ideally in-situ manipulation capabilities. Recent development of new Atomic Force Microscopy (AFM) capabilities has made it such a powerful tool for biological and biomedical research. This review introduces novel AFM functionalities including high-speed imaging for dynamic process visualization, mechanobiology with force spectroscopy, molecular species characterization, and AFM nano-manipulation. These capabilities enable many new possibilities for novel scientific research and allow scientists to observe and explore processes at the nanoscale like never before. Selected application examples from recent studies are provided to demonstrate the effectiveness of these AFM techniques.

With the recent advances in the field of nanotechnology, measurement and manipulation requirements at the nanoscale have become more stringent than ever before. In atomic force microscopy, high-speed performance alone is not sufficient without considerations of other aspects of the measurement task, such as the feature aspect ratio, required range, or acceptable probe-sample interaction forces. In this paper, the authors discuss these requirements and the research directions that provide the highest potential in meeting them. The authors elaborate on the efforts toward the downsizing of self-sensed and self-actuated probes as well as on upscaling by active cantilever arrays. The authors present the fabrication process of active probes along with the tip customizations carried out targeting specific application fields. As promising application in scope of nanofabrication, field emission scanning probe lithography is introduced. The authors further discuss their control and design approach. Here, microactuators, e.g., multilayer microcantilevers, and macroactuators, e.g., flexure scanners, are combined in order to simultaneously meet both the range and speed requirements of a new generation of scanning probe microscopes.

Piezoelectric hysteresis is a critical issue that significantly degrades the motion accuracy of piezo-actuated nanopositioners. Such an issue is difficult to be precisely modeled and compensated for, primarily due to its asymmetric, rate, and input amplitude-dependent characteristics. This article proposes a novel method to deal with this challenge. Specifically, a polynomial-based fractional order disturbance model is proposed to accommodate and characterize the complex hysteresis effect. In this model, the rate dependence is captured by a general method of implementing curve fitting in Bode magnitude plot. The inverse model for control purposes is immediately available from the original one. The proposed method does not require expensive computational resources. In fact, this article shows that this controller can be easily implemented in an analog manner, which brings the advantages of high bandwidth and low cost. Extensive modeling and tracking experiments are carried out to demonstrate the effectiveness of the proposed method. It is shown that the piezoelectric hysteresis nonlinearity can be significantly suppressed over a wide bandwidth.

Charge control is a well-known sensorless approach to operate piezoelectric actuators, which has been proposed for more than 30 years. However, it is rarely used in industry because the implemented controllers suffer from the issues of limited low-frequency performance, long settling time, floating-load, and loss of stroke, etc. In this paper, a novel controller circuit dedicated to overcome these issues is presented. In the proposed scheme, a grounded-load charge controller with decoupled configuration is developed, which separates high-frequency and low-frequency paths, thus achieving arbitrarily low transition frequency without increasing the settling time. Based on this, a self-compensating configuration is further proposed and integrated into the controller circuit, which makes full use of controller output to improve its own control performance at low frequencies. Experimental results show that the presented charge controller can effectively reduce more than 88% of the hysteretic nonlinearity even when operating close to the transition frequency. To demonstrate its practical value, we then integrate it into a custom-designed high-speed atomic force microscope system. By comparing images obtained from using voltage drive and charge controller, it is clear that the piezoelectric hysteresis has been significantly reduced in a wide bandwidth.