Large-range high-speed dynamic-mode atomic force microscope imaging: adaptive tapping towards minimal force.

In this paper, a software-hardware integrated approach is proposed for high-speed, large-range tapping mode imaging of atomic force microscope (AFM). High speed AFM imaging is needed in various applications, particularly in interrogating dynamic processes at nanoscale such as polymer crystallization process. Achieving high speed in tapping-mode AFM imaging is challenging as the probe-sample interaction during the imaging process is highly nonlinear, making the tapping motion highly sensitive to the probe sample spacing, and thereby, difficult to maintain at high speed. Increasing the speed via hardware bandwidth enlargement, however, leads to a substantially reduction of the imaging area. Contrarily, the imaging speed can be increased without loss of the scan size through control (algorithm)-based approach. For example, the recently-developed adaptive multiloop mode (AMLM) technique has demonstrated its efficacy in increasing the tapping-mode imaging speed without loss of scan size. Further improvement, however, has been limited by the hardware bandwidth and the online signal processing speed and computation complexity involved. Thus, in this paper, the AMLM technique is further enhanced to optimize the probe tapping regulation, and integrated with a field programmable gate array platform to further increase the imaging speed without loss of quality and scan range. Experimental implementation of the proposed approach demonstrates that high-quality imaging can be achieved at a high-speed scanning rate of 100 Hz and higher, and over a large imaging area of over 20µm.

Data-driven dynamics-based optimal filtering of acoustic noise at arbitrary location in atomic force microscope imaging.

This paper presents a post-filtering approach to eliminate distortions in atomic force microscope (AFM) images caused by acoustic noise from an unknown location. AFM operations are sensitive to external disturbances including acoustic noise, as disturbances to the probe-sample interaction directly results in distortions in the sample images obtained. Although conventional passive noise cancellation has been employed, limitation exists and residual noise still persists. Advanced online control techniques face difficulty in capturing the complex noise dynamic and limited system bandwidth imposed by robustness requirement. In this work, we propose a dynamics-based optimal filtering technique to remove the acoustic-caused distortions in AFM images. A dictionary-approach is integrated with time-delay measurement to localize the noise source and estimate the corresponding acoustic dynamics. Then a noise-to-image coherence minimization approach is proposed to minimize the acoustic-caused image distortion via a gradient-based optimization to seek an optimal modulator to the acoustic dynamics. Finally, the filter is obtained as the finite-impulse response of the optimized acoustic dynamics. Experimental implementation is presented and discussed to illustrate the proposed technique.

Self-limiting electrospray deposition on polymer templates.

Electrospray deposition (ESD) applies a high voltage to liquids flowing through narrow capillaries to produce monodisperse generations of droplets down to hundreds of nanometers in diameter, each carrying a small amount of the delivered solute. This deposition method has been combined with insulated stencil masks for fabricating micropatterns by spraying solutions containing nanoparticles, polymers, or biomaterials. To optimize the fabrication process for micro-coatings, a self-limiting electrospray deposition (SLED) method has recently been developed. Here, we combine SLED with a pre-existing patterned polymer film to study SLED's fundamental behavior in a bilayer geometry. SLED has been observed when glassy insulating materials are sprayed onto conductive substrates, where a thickness-limited film forms as charge accumulates and repels the arrival of additional charged droplets. In this study, polystyrene (PS), Parylene C, and SU-8 thin films of varying thickness on silicon are utilized as insulated spraying substrates. Polyvinylpyrrolidone (PVP), a thermoplastic polymer is sprayed below its glass transition temperature (Tg) to investigate the SLED behavior on the pre-deposited insulating films. Furthermore, to examine the effects of in-plane confinement on the spray, a microhole array patterned onto the PS thin film by laser dewetting was sprayed with dyed PVP in the SLED mode. This was then extended to an unmasked electrode array showing that masked SLED and laser dewetting could be used to target microscale regions of conventionally-patterned electronics.

Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration.

The regulatory mechanisms enabling the intestinal epithelium to maintain a high degree of regenerative capacity during mucosal injury remain unclear. Ex vivo survival and clonogenicity of intestinal stem cells (ISCs) strictly required growth response mediated by cell division control 42 (Cdc42) and Cdc42-deficient enteroids to undergo rapid apoptosis. Mechanistically, Cdc42 engaging with EGFR was required for EGF-stimulated, receptor-mediated endocytosis and sufficient to promote MAPK signaling. Proteomics and kinase analysis revealed that a physiologically, but nonconventionally, spliced Cdc42 variant 2 (V2) exhibited stronger MAPK-activating capability. Human CDC42-V2 is transcriptionally elevated in some colon tumor tissues. Accordingly, mice engineered to overexpress Cdc42-V2 in intestinal epithelium showed elevated MAPK signaling, enhanced regeneration, and reduced mucosal damage in response to irradiation. Overproducing Cdc42-V2 specifically in mouse ISCs enhanced intestinal regeneration following injury. Thus, the intrinsic Cdc42-MAPK program is required for intestinal epithelial regeneration, and elevating this signaling cascade is capable of initiating protection from genotoxic injury.

Rapid broadband discrete nanomechanical mapping of soft samples on atomic force microscope.

In this paper, an approach to achieve rapid broadband discrete nanomechanical mapping of soft samples using an atomic force microscope is developed. Nanomechanical mapping (NM) is needed to investigate, for example, dynamic evolution of the nanomechanical distribution of the sample-provided that the mapping is fast enough. The throughput of conventional NM methods, however, is inherently limited by the continuous scanning involved where the probe visits each sampling location continuously. Thus, we propose to significantly reduce the number of measurements through discrete mapping where only discrete sampling locations of interests are visited and measured. An online-searching learning-based technique is utilized to achieve rapid probe engagement and withdrawal with the interaction force minimized at each sampling location. Then, a control-based nanoindentation measurement technique is used to quickly acquire the nanomechanical property at each location, over frequencies that can be chosen arbitrarily in a broad range. Finally, a decomposition-based learning approach is explored to achieve rapid probe transitions between the sampling locations. The proposed technique is demonstrated through experiments using a Polydimethylsiloxane (PDMS) sample and a PDMS-epoxy sample as examples.

Active control of acoustics-caused nano-vibration in atomic force microscope imaging.

In this paper, we propose a finite-impulse-response (FIR)-based feedforward control approach to mitigate the acoustic-caused probe vibration during atomic force microscope (AFM) imaging. Compensation for the acoustic-caused probe vibration is important, as environmental disturbances including acoustic noise induce nano-scale probe vibration, directly affecting the AFM performance in applications such as imaging, nanomechanical characterization, and nanomanipulation. Although conventional passive noise cancellation apparatus has been employed, limitation exists, and residual noise still persists. Thus, a FIR-based active feedforward control approach is developed, by exploring a data-driven approach to account for the vibrational dynamics of the probe caused by the environmental acoustic noise in the controller design. An experimental implementation in AFM imaging application is presented and discussed to illustrate the proposed technique. Experimental results show that the FIR-based feedforward control is promising to not only complement, but also alleviate the limitations of passive noise control in AFM operations.

Adaptive-scanning, near-minimum-deformation atomic force microscope imaging of soft sample in liquid: Live mammalian cell example.

In this paper, an adaptive-scanning mode (ASM) of atomic force microscope (AFM) with near-minimum sample deformation is proposed for imaging live biological samples in liquid. Conventional contact mode (CM) imaging of live cells is rather slow (scan rate  <  0.2 Hz), and as the imaging speed increases, significant deformation of the soft and highly corrugated cell membrane is induced. Such a low speed CM imaging of live biological samples is not only time consuming, but also incapable of capturing dynamic biological evolutions occurring in seconds to minutes. The proposed ASM approach aims to address these issues through two synergetic efforts integrated together. First, an adaptive-scanning technique is proposed to optimally adjust the lateral scanning speed to accommodate the sample topography variation and the probe-sample interaction force, so that the scanning-caused sample deformation is maintained below the threshold value while the overall imaging time is minimized. Secondly, a data-driven iterative feedforward control is integrated to the vertical feedback loop along with a gradient-based optimization of the deflection set-point to substantially improve the tracking of the sample topography while maintaining the vertical sample deformation around the minimal. The ASM technique is experimentally validated through imaging live human prostate cancer cells on AFM. The experimental results demonstrate that compared to the conventional CM imaging, the imaging speed is increased over eight times without loss of tracking the topography details of the live cell membrane, and the probe-sample interaction force is substantially reduced.

Receptor-mediated endocytosis generates nanomechanical force reflective of ligand identity and cellular property.

Whether environmental (thermal, chemical, and nutrient) signals generate quantifiable, nanoscale, mechanophysical changes in the cellular plasma membrane has not been well elucidated. Assessment of such mechanophysical properties of plasma membrane may shed lights on fundamental cellular process. Atomic force microscopic (AFM) measurement of the mechanical properties of live cells was hampered by the difficulty in accounting for the effects of the cantilever motion and the associated hydrodynamic force on the mechanical measurement. These challenges have been addressed in our recently developed control-based AFM nanomechanical measurement protocol, which enables a fast, noninvasive, broadband measurement of the real-time changes in plasma membrane elasticity in live cells. Here we show using this newly developed AFM platform that the plasma membrane of live mammalian cells exhibits a constant and quantifiable nanomechanical property, the membrane elasticity. This mechanical property sensitively changes in response to environmental factors, such as the thermal, chemical, and growth factor stimuli. We demonstrate that different chemical inhibitors of endocytosis elicit distinct changes in plasma membrane elastic modulus reflecting their specific molecular actions on the lipid configuration or the endocytic machinery. Interestingly, two different growth factors, EGF and Wnt3a, elicited distinct elastic force profiles revealed by AFM at the plasma membrane during receptor-mediated endocytosis. By applying this platform to genetically modified cells, we uncovered a previously unknown contribution of Cdc42, a key component of the cellular trafficking network, to EGF-stimulated endocytosis at plasma membrane. Together, this nanomechanical AFM study establishes an important foundation that is expandable and adaptable for investigation of cellular membrane evolution in response to various key extracellular signals.

Simultaneous topography imaging and broadband nanomechanical mapping on atomic force microscope.

In this paper, an approach is proposed to achieve simultaneous imaging and broadband nanomechanical mapping of soft materials in air by using an atomic force microscope. Simultaneous imaging and nanomechanical mapping are needed, for example, to correlate the morphological and mechanical evolutions of the sample during dynamic phenomena such as the cell endocytosis process. Current techniques for nanomechanical mapping, however, are only capable of capturing static elasticity of the material, or the material viscoelasticity in a narrow frequency band around the resonant frequency(ies) of the cantilever used, not competent for broadband nanomechanical mapping, nor acquiring topography image of the sample simultaneously. These limitations are addressed in this work by enabling the augmentation of an excitation force stimuli of rich frequency spectrum for nanomechanical mapping in the imaging process. Kalman-filtering technique is exploited to decouple and split the mixed signals for imaging and mapping, respectively. Then the sample indentation generated is quantified online via a system-inversion method, and the effects of the indentation generated and the topography tracking error on the topography quantification are taken into account. Moreover, a data-driven feedforward-feedback control is utilized to track the sample topography. The proposed approach is illustrated through experimental implementation on a polydimethylsiloxane sample with a pre-fabricated pattern.

High-speed dynamic-mode atomic force microscopy imaging of polymers: an adaptive multiloop-mode approach.

Adaptive multiloop-mode (AMLM) imaging to substantially increase (over an order of magnitude) the speed of tapping-mode (TM) imaging is tested and evaluated through imaging three largely different heterogeneous polymer samples in experiments. It has been demonstrated that AMLM imaging, through the combination of a suite of advanced control techniques, is promising to achieve high-speed dynamic-mode atomic force microscopy imaging. The performance, usability, and robustness of the AMLM in various imaging applications, however, is yet to be assessed. In this work, three benchmark polymer samples, including a PS-LDPE sample, an SBS sample, and a Celgard sample, differing in feature size and stiffness of two orders of magnitude, are imaged using the AMLM technique at high-speeds of 25 Hz and 20 Hz, respectively. The comparison of the images obtained to those obtained by using TM imaging at scan rates of 1 Hz and 2 Hz showed that the quality of the 25 Hz and 20 Hz AMLM imaging is at the same level of that of the 1 Hz TM imaging, while the tip-sample interaction force is substantially smaller than that of the 2 Hz TM imaging.

High-speed broadband monitoring of cell viscoelasticity in real time shows myosin-dependent oscillations.

Study of the dynamic evolutions of cell viscoelasticity is important as during cell activities such as cell metastasis and invasion, the rheological behaviors of the cells also change dynamically, reflecting the biophysical and biochemical connections between the outer cortex and the intracellular structures. Although the time variations of the static modulus of cells have been investigated, few studies have been reported on the dynamic variations of the frequency-dependent viscoelasticity of cells. Measuring and monitoring such dynamic evolutions of cells at nanoscale can be challenging as the measurement needs to meet two objectives inherently contradictory to each other-the measurement must be broadband (to cover a large frequency spectrum) but also rapid (to capture the time-elapsed changes). In this study, we exploited a recently developed control-based nanomechanical protocol of atomic force microscope to monitor in real time the dynamic evolutions of the viscoelasticity of live human prostate cancer cells (PC-3 cells) and study its dependence on myosin activities. We found that the viscoelasticity of PC-3 cells, followed the power law, and oscillated at a period of about 200 s. Both the amplitude and the frequency of the oscillation strongly depended on the intracellular calcium and blebbistatin-sensitive motor proteins.

Study of Cholesterol Repletion Effect on Nanomechanical Properties of Human Umbilical Vein Endothelial Cell Via Rapid Broadband Atomic Force Microscopy.

Abnormalities of blood cholesterol concentration are associated with increased risks for vascular disease, especially heart attacks and strokes. As one of the main lipid components of plasma membrane in all mammalian cells, cholesterol has a major impact on the mechanical properties of the membrane of endothelial cells. Although the effect of cholesterol depletion on cell mechanical properties has been studied, no results yet have been reported on quantitative investigation of cholesterol repletion effect. In this study, the cholesterol repletion effect on the nanomechanical properties of human umbilical vein endothelial cell (EA.hy926) was studied using a control-based atomic force microscope (AFM) nanomechanical measurement protocol. The viscoelasticity of EA.hy926 cells were measured over a large frequency range (0.1-100 Hz) using both constant-rate excitation force with different loading rates and a broadband excitation force. The viscoelasticity oscillation of the cell membranes under the cholesterol effect was also monitored in real-time. The experiment results showed that under the effect of cholesterol repletion, both the Young's modulus and the complex modulus of EA.hy926 cell were increased over 30%, respectively, and moreover, the amplitudes of both the elasticity oscillation and the viscosity oscillation at a period of around 200 s were increased over 70%, respectively. Therefore, this work is among the first to investigate the mechanical properties, particularly, the broadband viscoelasticity variations of EA.hy926 cells under cholesterol repletion treatment. The results revealed that cholesterol repletion may reinforce the coupling of F-actin to plasma membrane by increasing actin stability, and the cholesterol might have modified the submembrane cytoskeletal organization of EA.hy926 cell by causing the involvement of the motor protein nonmuscle myosin II.

An Atomic Force Microscope Study Revealed Two Mechanisms in the Effect of Anticancer Drugs on Rate-Dependent Young's Modulus of Human Prostate Cancer Cells.

Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3) are investigated using a recently developed control-based nanoindentation measurement (CNM) protocol on atomic force microscope (AFM). The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young's modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young's modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.

High-speed adaptive contact-mode atomic force microscopy imaging with near-minimum-force.

In this paper, an adaptive contact-mode imaging approach is proposed to replace the traditional contact-mode imaging by addressing the major concerns in both the speed and the force exerted to the sample. The speed of the traditional contact-mode imaging is largely limited by the need to maintain precision tracking of the sample topography over the entire imaged sample surface, while large image distortion and excessive probe-sample interaction force occur during high-speed imaging. In this work, first, the image distortion caused by the topography tracking error is accounted for in the topography quantification. Second, the quantified sample topography is utilized in a gradient-based optimization method to adjust the cantilever deflection set-point for each scanline closely around the minimal level needed for maintaining stable probe-sample contact, and a data-driven iterative feedforward control that utilizes a prediction of the next-line topography is integrated to the topography feeedback loop to enhance the sample topography tracking. The proposed approach is demonstrated and evaluated through imaging a calibration sample of square pitches at both high speeds (e.g., scan rate of 75 Hz and 130 Hz) and large sizes (e.g., scan size of 30 µm and 80 µm). The experimental results show that compared to the traditional constant-force contact-mode imaging, the imaging speed can be increased by over 30 folds (with the scanning speed at 13 mm/s), and the probe-sample interaction force can be reduced by more than 15% while maintaining the same image quality.

High-speed atomic force microscope imaging: adaptive multiloop mode.

In this paper, an imaging mode (called the adaptive multiloop mode) of atomic force microscope (AFM) is proposed to substantially increase the speed of tapping mode (TM) imaging while preserving the advantages of TM imaging over contact mode (CM) imaging. Due to its superior image quality and less sample disturbances over CM imaging, particularly for soft materials such as polymers, TM imaging is currently the most widely used imaging technique. The speed of TM imaging, however, is substantially (over an order of magnitude) lower than that of CM imaging, becoming the major bottleneck of this technique. Increasing the speed of TM imaging is challenging as a stable probe tapping on the sample surface must be maintained to preserve the image quality, whereas the probe tapping is rather sensitive to the sample topography variation. As a result, the increase of imaging speed can quickly lead to loss of the probe-sample contact and/or annihilation of the probe tapping, resulting in image distortion and/or sample deformation. The proposed adaptive multiloop mode (AMLM) imaging overcomes these limitations of TM imaging through the following three efforts integrated together: First, it is proposed to account for the variation of the TM deflection when quantifying the sample topography; second, an inner-outer feedback control loop to regulate the TM deflection is added on top of the tapping-feedback control loop to improve the sample topography tracking; and, third, an online iterative feedforward controller is augmented to the whole control system to further enhance the topography tracking, where the next-line sample topography is predicted and utilized to reduce the tracking error. The added feedback regulation of the TM deflection ensures the probe-sample interaction force remains near the minimum for maintaining a stable probe-sample interaction. The proposed AMLM imaging is tested and demonstrated by imaging a poly(tert-butyl acrylate) sample in experiments. The experimental results demonstrate that the image quality achieved by using the proposed AMLM imaging at a scan rate of 25 Hz and over a large-size imaging (50 µm × 25 µm) is at the same level of that obtained using TM imaging at 1 Hz, while the probe-sample interaction force is noticeably reduced from that achieved using TM imaging at 2.5 Hz.

Mechanical-plowing-based high-speed patterning on hard material via advanced-control and ultrasonic probe vibration.

In this paper, we present a high-speed direct pattern fabrication on hard materials (e.g., a tungsten-coated quartz substrate) via mechanical plowing. Compared to other probe-based nanolithography techniques based on chemical- and/or physical-reactions (e.g., the Dip-pen technique), mechanical plowing is meritorious for its low cost, ease of process control, and capability of working with a wide variety of materials beyond conductive and/or soft materials. However, direct patterning on hard material faces two daunting challenges. First, the patterning throughput is ultimately hindered by the "writing" (plowing) speed, which, in turn, is limited by the adverse effects that can be excited/induced during high-speed, and/or large-range plowing, including the vibrational dynamics of the actuation system (the piezoelectric actuator, the cantilever, and the mechanical fixture connecting the cantilever to the actuator), the dynamic cross-axis coupling between different axes of motion, and the hysteresis and the drift effects related to the piezoelectric actuators. Secondly, it is very challenging to directly pattern on ultra-hard materials via plowing. Even with a diamond probe, the line depth of the pattern via continuous plowing on ultra-hard materials such as tungsten, is still rather small (<0.5 nm), particularly when the "writing" speed becomes high. To overcome these two challenges, we propose to utilize a novel iterative learning control technique to achieve precision tracking of the desired pattern during high-speed, large-range plowing, and introduce ultrasonic vibration of the probe in the normal (vertical) direction during the plowing process to enable direct patterning on ultra hard materials. The proposed approach was implemented to directly fabricate patterns on a mask with tungsten coating and quartz substrate. The experimental results demonstrated that a large-size pattern of four grooves (20 µm in length with 300 nm spacing between lines) can be fabricated at a high speed of ~5 mm/s, with the line width and the line depth at ~95 nm and 2 nm, respectively. A fine pattern of the word "NANO" is also fabricated at the speed of ~5 mm/s.

Indentation quantification for in-liquid nanomechanical measurement of soft material using an atomic force microscope: rate-dependent elastic modulus of live cells.

In this paper, a control-based approach to replace the conventional method to achieve accurate indentation quantification is proposed for nanomechanical measurement of live cells using atomic force microscope. Accurate indentation quantification is central to probe-based nanomechanical property measurement. The conventional method for in-liquid nanomechanical measurement of live cells, however, fails to accurately quantify the indentation as effects of the relative probe acceleration and the hydrodynamic force are not addressed. As a result, significant errors and uncertainties are induced in the nanomechanical properties measured. In this paper, a control-based approach is proposed to account for these adverse effects by tracking the same excitation force profile on both a live cell and a hard reference sample through the use of an advanced control technique, and by quantifying the indentation from the difference of the cantilever base displacement in these two measurements. The proposed control-based approach not only eliminates the relative probe acceleration effect with no need to calibrate the parameters involved, but it also reduces the hydrodynamic force effect significantly when the force load rate becomes high. We further hypothesize that, by using the proposed control-based approach, the rate-dependent elastic modulus of live human epithelial cells under different stress conditions can be reliably quantified to predict the elasticity evolution of cell membranes, and hence can be used to predict cellular behaviors. By implementing the proposed approach, the elastic modulus of HeLa cells before and after the stress process were quantified as the force load rate was changed over three orders of magnitude from 0.1 to 100 Hz, where the amplitude of the applied force and the indentation were at 0.4-2 nN and 250-450 nm, respectively. The measured elastic modulus of HeLa cells showed a clear power-law dependence on the load rate, both before and after the stress process. Moreover, the elastic modulus of HeLa cells was substantially reduced by two to five times due to the stress process. Thus, our measurements demonstrate that the control-based protocol is effective in quantifying and characterizing the evolution of nanomechanical properties during the stress process of live cells.

Macroscopic highly aligned DNA nanowires created by controlled evaporative self-assembly.

By subjecting DNA aqueous solution to evaporate in a curve-on-flat geometry that was composed of either a spherical lens or a cylindrical lens situated on a flat substrate, a set of highly aligned DNA nanowires in the forms of spokes and parallel stripes over a macroscopic area (i.e., millimeter scale) were successfully created. The DNA molecules were stretched and aligned on polymer-coated substrate by the receding meniscus. The imposed curve-on-flat geometry provided a unique environment for controlling the flow within the evaporating solution by eliminating temperature gradient and possible convective instability and, thus, regulated the formation of DNA nanowires. Such controlled evaporative self-assembly is remarkably easy to implement and opens up a new avenue for crafting large-scale DNA-based nanostructures in a simple and cost-effective manner, dispensing with the need for lithography techniques.

High-speed force load in force measurement in liquid using scanning probe microscope.

This article presents an inversion-based iterative feedforward-feedback (II-FF/FB) approach to achieve high-speed force load in force measurement of soft materials in liquid using scanning probe microscope (SPM). SPM force measurement under liquid environment is needed to interrogate a wide range of soft materials, particularly live biological samples. Moreover, when dynamic evolution of the sample occurs during the measurement, and/or measuring the rate-dependent viscoelasticity of the sample, the force measurement also needs to be acquired at high-speed. Precision force load in liquid, however, is challenged by adverse effects including the thermal drift effect, the reduction of the signal to noise ratio, the distributive hydrodynamic force effect, and the hysteresis and vibrational dynamics effects of the piezoelectric actuators (for positioning the probe relative to the sample), particularly during high-speed measurement. Thus, the main contribution of the article is the development of the II-FF/FB approach to tackle these challenges. The proposed method is illustrated through an experimental implementation to the force-curve measurement of a poly (dimethylsiloxane) sample in liquid at high-speed.