Quantitative Force Measurements Research Articles

Characterization of strongly coupled quartz tuning fork sensors for precision force measurement in atomic force microscopy

Miniaturized quartz tuning forks (QTFs) have been adopted as force sensors for non-contact atomic force microscopy (AFM). However, the coupled oscillation behaviors of the QTF prongs are not well understood, preventing quantitative measurement of the nanoscale tip-sample interaction forces. This article presents a lumped model that accurately delineates the coupled mechanical oscillations of QTF prongs, establishing rigorous relationships between experimental observables and tip-sample interaction forces. The first-order resonance spectra of a commercial QTF were fully characterized by correlating its piezoelectric response with the actual mechanical oscillation measured with a Fabry-Pérot interferometer. In order to uniquely determine the modeling parameters (i.e., the effective masses, spring constants, and damping constants), the experimental results were compared with the lumped model predictions while masses were added to one prong. The results reveal that the QTF’s center of mass is highly damped, preventing the observation of a symmetric resonance mode. In addition, the mass loading experiment demonstrates that the mechanical oscillations of the QTF prongs are strongly coupled, accounting for 59% (84%) of the effective stiffness at the in-plane (out-of-plane), antisymmetric resonance mode. We believe that the obtained QTF characterization results will pave the way for quantitative measurements of non-contact interaction forces in QTF-based AFM platforms, significantly improving the precision and reliability of nanoscale force measurements.

Facile Mechanophore Integration in Heterogeneous Biologically Derived Materials via "Dip-Conjugation".

Mechanical forces play critical roles in a wide variety of biological processes and diseases, yet measuring them directly at the molecular level remains one of the main challenges of mechanobiology. Here, we show a strategy to "Dip-conjugate" biologically derived materials at the chemical level to mechanophores, force-responsive molecular entities, using Click-chemistry. Contrary to classical prepolymerization mechanophore incorporation, this new protocol leads to detectable mechanochromic response with as low as 5% strain, finally making mechanophores relevant for many biological processes that have previously been inaccessible. Our results demonstrate the ubiquity of the technique with activation in synthetic polymers, carbohydrates, and proteins under mechanical force, with alpaca wool fibers as a key example. These results push the limits for mechanophore use in far more types of polymeric materials in applications ranging from molecular-level force damage detection to direct and quantitative 3D force measurements in mechanobiology.

Direct force measurements between sub-micron rod-shaped colloids by AFM

The colloidal probe (CP) technique is an essential tool for quantitative direct force measurements by atomic force microscopy (AFM). By attaching a colloidal particle to the free end of an AFM-cantilever, not only a defined interaction geometry can be accomplished, but also a nearly arbitrary surface chemistry becomes possible. Commonly, the CP-technique is utilized for spherical particles in the sphere/sphere or sphere/plane interaction geometry. Here, the CP-technique has been extended to rod-shaped colloids with diameters well below one micrometer, thus preparing ‘rod probes’ based on a procedure similar to that known from DNA combing, allowing for a controlled alignment between these rods and the rod probe. In combination with AFM-imaging by the rod on the probe, sufficiently orthogonally aligned pairs of rods can be identified, and direct force measurements in the crossed-cylinder geometry, similar to the surface force apparatus (SFA), can be accomplished. A proof-of-concept of direct force measurements between silica rods with diameters of 270 ± 50 nm has been presented. The acquired interaction force profiles have been quantitatively evaluated within the framework of the full solutions of the Poisson-Boltzmann equation, including charge regulation.

Efficacy of microchips and 3D sensors for orthodontic force measurement: A systematic review of invitro studies.

To evaluate the efficacy of microchips and 3D microsensors in the measurement of orthodontic forces. Through September 2023, comprehensive searches were conducted on PubMed/MEDLINE, SCOPUS and SCIELO without restrictions. After removing duplicate entries and applying the eligibility criteria, 23 studies were included for analysis. All the studies were conducted invitro, and slightly more than half of them were centred on evaluating orthodontic forces exerted by aligners. Eight utilized microchips as measurement tools, while the remaining studies made use of 3D microsensors for their assessments. In the context of fixed appliances, key findings included a high level of agreement in 3-dimensional orthodontic force detection between simulation results and actual applied forces. Incorporating critical force-moment combinations during smart bracket calibration reduced measurement errors for most components. Translational tooth movement revealed a moment-to-force ratio, aligning with the bracket's centre of resistance. The primary findings in relation to aligners revealed several significant factors affecting the forces exerted by them. Notably, the foil thickness and staging were found to have a considerable impact on these forces, with optimal force transmission occurring at a layer height of 150 μm. Furthermore, the type of material used in 3D-printing aligners influenced the force levels, with attachments proving effective in generating extrusive forces. Deliberate adjustments in aligner thickness were observed to alter the forces and moments generated. Microchips and 3D sensors provide precise and quantitative measurements of orthodontic forces in invitro studies, enabling accurate monitoring and control of tooth movement.

Quantitative radial force measurements of Woven EndoBridge devices.

Lateral/radial forces and the mechanical properties of Woven EndoBridge (WEB) devices have significant importance for therapeutic success. In other words, adequate apposition of the lateral wall of a cerebral aneurysm is critical for preventing recurrence or re-rupture risk. This study aimed to investigate the pressure values applied by different WEB devices to the lateral walls of aneurysms and the relationships between these pressure measurements and the diameters of WEB devices. By placing four WEB devices of different sizes and types between two rigid metal plates, the lateral forces applied by these WEB devices to plates of different apertures were measured quantitatively. We tested a single device of each size over multiple periods. The total number of examined WEB devices is four. There was a significant negative relationship between plate distances and pressure values (correlation coefficient:-0.956, p = 0.000). The lateral wall apposition pressure of a 4- or 5-mm aperture size was higher than a 6-mm aperture size for SL-type WEB devices with a 7-mm diameter. Similarly, the lateral wall apposition pressure detected for a 3- or 3.5-mm aperture size was higher than a 4-mm aperture size for W5-4.5-3 and W5-5-3.6. It was observed that maximum lateral wall pressure was detected in plate measurements of SLS-type devices compared to SL-type devices. The diameter and height values of 3 of the 4 unconstrained WEB devices analyzed differed from the catalog values. It seems that SLS-type devices apply more pressure on the aneurysm's lateral borders than SL-type devices.

Endotracheal tube forces exerted on the larynx and a novel support device to reduce it.

Endotracheal tubes (ETTs) are commonly associated with laryngeal injury that may be short lasting and temporary or more severe and life altering. Injury is believed to result from forces that these ETTs exert on the larynx. Here we quantify the forces of ETTs of various sizes on the laryngotracheal complex to gain a more quantitative understanding of these potential damaging forces. Here we also perform preclinical testing of a novel support device to offload these forces. Endotracheal intubation was performed on a fresh human cadaver using various ETT sizes. A strain-sensitive graphene nanosheet sensor and a commercially available force sensing resistor were secured behind the larynx, anterior to the prevertebral fascia. The forces exerted on the larynx were measured for each of the commonly used ETTs. A novel support device, ETT clip (Endo Clip), was attached to the ETTs and changes in these forces were observed. Forces exerted on the laryngotracheal complex by various ETTs were observed to increase with increasing tube size. This pressure can be significantly reduced with a novel ETT clip. Here we demonstrate the first quantitative measurement of forces that ETTs exert on the larynx. We demonstrate a novel device that can easily clip onto an ETT reducing pressure on the laryngotracheal complex. This preclinical test paves the way for a human clinical trial. 5.

Reconstitution of Organelle Transport Along Microtubules In Vitro.

In this chapter, we describe methods for reconstituting and analyzing the transport of isolated endogenous cargoes in vitro. Intracellular cargoes are transported along microtubules by teams of kinesin and dynein motors and their cargo-specific adaptor proteins. Observations from living cells show that organelles and vesicular cargoes exhibit diverse motility characteristics. Yet, our knowledge of the molecular mechanisms by which intracellular transport is regulated is not well understood. Here, we describe step-by-step protocols for the extraction of phagosomes from cells at different stages of maturation, and reconstitution of their motility along microtubules in vitro. Quantitative immunofluorescence and photobleaching techniques are also described to measure the number of motors and adaptor proteins on these isolated cargoes. In addition, we describe techniques for tracking the motility of isolated cargoes along microtubules using TIRF microscopy and quantitative force measurements using an optical trap. These methods enable us to study how the sets of motors and adaptors that drive the transport of endogenous cargoes regulate their trafficking in cells.

In Vivo Trapping of Latex Bead Phagosomes for Quantitative Force Measurements.

Optical trapping of organelles inside cells is a powerful technique for directly measuring the forces generated by motor proteins when they are transporting the organelle in the form of a "cargo". Such experiments provide an understanding of how multiple motors (similar or dissimilar) function in their endogenous environment. Here we describe the use of latex bead phagosomes ingested by macrophage cells as a model cargo for optical trap-based force measurements. A protocol for quantitative force measurements of microtubule-based motors (dynein and kinesins) inside macrophage cells is provided.

Using colloidal AFM probe technique and XDLVO theory to predict the transport of nanoplastics in porous media

The plastic concentration in terrestrial systems is orders of magnitude higher than that found in marine ecosystems, which has raised global concerns about their potential risk to agricultural sustainability. Previous research on the transport of nanoplastics in soil relied heavily on the qualitative prediction of the mean-field extended Derjaguin–Landau–Verwey–Overbeek theory (XDLVO), but direct and quantitative measurements of the interfacial forces between single nanoplastics and porous media are lacking. In this study, we conducted multiscale investigations ranging from column transport experiments to single particle measurements. The maximum effluent concentration (C/C0) of amino-modified nanoplastics (PS–NH2) was 0.94, whereas that of the carboxyl-modified nanoplastics (PS–COOH) was only 0.33, indicating PS-NH2 were more mobile than PS-COOH at different ionic strengths (1–50 mM) and pH values (5–9). This phenomenon was mainly attributed to the homogeneous aggregation of PS-COOH. In addition, the transport of PS-NH2 in the quartz sand column was inhibited with the increase of ionic strength and pH, and pH was the major factor governing their mobility. The transport of PS-COOH was inhibited with increasing ionic strength and decreasing pH. Hydrophilicity/hydrophobicity-mediated interactions and particle heterogeneity strongly interfered with interfacial forces, leading to the qualitative prediction of XDLVO, contrary to experimental observations. Through the combination of XDLVO and colloidal atomic force microscopy, accurate and quantitative interfacial forces can provide compelling insight into the fate of nanoparticles in the soil environment.

Measurement of Intangible Human Elements in Determining Military Combat Readiness

Combat readiness is a composite concept that encompasses both tangible military logistics and intangible human components associated with soldiers preparing for combat missions. Militaries throughout the world define combat readiness as their military doctrine, policies, and public communications being in place to prepare their military troops for combat responsibilities. Situational Force Scoring (SFS) is a quantitative tangible measurement of forces' combat readiness in which numerical tangible scores are assigned based on logistics and manpower required percentages. To complete the equations for combat readiness, this research will identify and quantify the soldier's intangible human components of intangible combat readiness in the areas of morale, quality of life, and military psychological aspects, along with four antecedents for each domain. This quantitative study demonstrates military troops from operating units of the Royal Malaysian Navy and Royal Malaysian Air Force throughout Malaysia. The model was statistically validated against the data (n = 2466) using PLS-SEM. The findings reveal that external characteristics such as morale, quality of life, and psychological well-being account for 62.9 percent of intangible combat readiness. The results reveal that morale (= 0.578) has a greater direct effect on the measure of combat readiness than psychological factors (= 0.171) or quality of life factors (= 0.091). Morale is a critical component in intangible combat readiness enhancement. The findings indicate that boosting efforts to improve personnel morale will undoubtedly improve the Malaysian Armed Forces' soldiers' intangible combat readiness. Efforts to enhance the effectiveness of quality of life and psychological issues must be prioritised.

Modulating Surface Properties of the Linothele fallax Spider Web by Solvent Treatment.

Linothele fallax (Mello-Leitão) (L. fallax) spider web, a potentially attractive tissue engineering material, was investigated using quantitative peak force measurement atomic force microscopy and scanning electron microscopy with energy dispersive spectroscopy both in its natural state and after treatment with solvents of different protein affinities, namely, water, ethanol, and dimethyl sulfoxide (DMSO). Native L. fallax silk threads are densely covered by globular objects, which constitute their inseparable parts. Depending on the solvent, treating L. fallax modifies its appearance. In the case of water and ethanol, the changes are minor. In contrast, DMSO practically removes the globules and fuses the threads into dense bands. Moreover, the solvent treatment influences the chemistry of the threads’ surface, changing their adhesive and, therefore, biocompatibility and cell adhesion properties. On the other hand, the solvent-treated web materials’ contact effect on different types of biological matter differs considerably. Protein-rich matter controls humidity better when wrapped in spider silk treated with more hydrophobic solvents. However, carbohydrate plant materials retain more moisture when wrapped in native spider silk. The extracts produced with the solvents were analyzed using nuclear magnetic resonance (NMR) and liquid chromatography–mass spectrometry techniques, revealing unsaturated fatty acids as representative adsorbed species, which may explain the mild antibacterial effect of the spider silk. The extracted metabolites were similar for the different solvents, meaning that the globules were not “dissolved” but “fused into” the threads themselves, being supposedly rolled-in knots of the protein chain.

Abstract 1166: Structurally defined glycosaminoglycan mimetics exhibit preference for proteins of the growth factor family

Abstract Heparan sulfate (HS), a glycosaminoglycans of considerable structural diversity, has been implicated in a wide-variety of complex roles including regulation of cell signaling. Unfortunately, homogeneous HS is a dream that will likely be unfulfilled this century. To combat this, our lab has synthesized an array of non-saccharide glycosaminoglycan mimetics (NSGMs) that act as structural and functional mimetics of HS. A key advantage of our NSGMs is homogeneity, which enables assessing selectivity for recognition of target proteins with a high degree of confidence. A second advantage is the quantitative measurement of the affinity of these interactions, which affords a detailed understanding of the forces governing recognition of different proteins. Previously, we have shown a lead NSGM named G2.2 as a potent and selective inhibitor of colorectal cancer stem cells (CSCs) through phenotypic in-vitro and in-vivo assays. To improve upon the drug-like properties of G2.2, cholesterol-modified analogs (G2C, G5C, G8C) were designed to enhance potency and selectivity for protein target(s). Although the hypothesis is that G2.2 and its lipidic analogs target a ligand and/or a receptor belonging to CSC-relevant growth factors, the preferred target, if any, remains to be identified. More importantly, the relative order of preference in-vitro and its use in predicted in-vivo activity remains to be determined. In this work, we have performed a comprehensive biophysical screening of a panel of potential growth factor targets using biophysical methods to determine binding affinities, followed by quantitative measurement of the relative forces of interactions involved in target recognition. Our studies are complemented by computational experiments that provide a foundation for thermodynamic studies. Analysis of our results indicate that these NSGMs preferentially recognize certain growth factor proteins, suggesting that appropriately designed HS mimetics can be tailored to modulate a particular tyrosine kinase receptor pathway. More importantly, our results convey the principle that despite the presence of multiple sulfate groups, HS mimetics can be designed to exhibit selectivity for certain growth factor proteins. In fact, the sulfate groups on our molecules may actually contribute to the selectivity and potency of recognition, two central principles for the development of drugs. Citation Format: Connor P. O'Hara, Nehru V. Sankaranarayanan, Rio S. Boothello, Bhaumik B. Patel, Umesh R. Desai. Structurally defined glycosaminoglycan mimetics exhibit preference for proteins of the growth factor family [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1166.

Confronting interatomic force measurements.

The quantitative interatomic force measurements open a new pathway to materials characterization, surface science, and chemistry by elucidating the tip-sample interaction forces. Atomic force microscopy is the ideal platform to gauge interatomic forces between the tip and the sample. For such quantitative measurements, either the oscillation frequency or the oscillation amplitude and the phase of a vibrating cantilever are recorded as a function of the tip-sample separation. These experimental quantities are subsequently converted into the tip-sample interaction force, which can be compared with interatomic force laws to reveal the governing physical phenomena. Recently, it has been shown that the most commonly applied mathematical conversion techniques may suffer a significant deviation from the actual tip-sample interaction forces. To avoid the assessment of unphysical interatomic forces, the use of either very small (i.e., a few picometers) or very large oscillation amplitudes (i.e., a few nanometers) has been proposed. However, the use of marginal oscillation amplitudes gives rise to another problem as it lacks the feasibility due to the adverse signal-to-noise ratios. Here, we show a new mathematical conversion principle that confronts interatomic force measurements while preserving the oscillation amplitude within the experimentally achievable and favorable limits, i.e., tens of picometers. Our theoretical calculations and complementary experimental results demonstrate that the proposed technique has three major advantages over existing methodologies: (I) eliminating mathematical instabilities of the reconstruction of tip-sample interaction force, (II) enabling accurate conversion deep into the repulsive regime of tip-sample interaction force, and (III) being robust to the uncertainty of the oscillation amplitude and the measurement noise. Due to these advantages, we anticipate that our methodology will be the nucleus of a reliable evaluation of material properties with a more accurate measurement of tip-sample interaction forces.

Trapping performance of holographic optical tweezers generated with different hologram algorithms

Quantitative measurement of small forces and small displacement using holographic optical tweezers (HOTs) is finding increasing applications due to the features of non-contact and high accuracy manipulation. Although hologram optimization algorithms have been widely reported, the holographic optical trapping performance relying on the algorithms has not been studied systematically. In this paper, we investigated the force measuring the performance of various types of HOTs generated with six different hologram algorithms (GSW, GAA, GS, SR, S, and RM). To do this, we built up a HOT instrument and compared the light fields’ intensity distribution, trap stiffness, efficiency, and calculation time of multi-point trap arrays generated by six hologram algorithms with this setup. Our work will provide a better understanding of the performance of different hologram algorithms in HOTs.

Nanomechanical Insights into Versatile Polydopamine Wet Adhesive Interacting with Liquid-Infused and Solid Slippery Surfaces.

Mussel-inspired polydopamine (PDA) can be readily deposited on almost all kinds of substrates and possesses versatile wet adhesion. Meanwhile, slippery surfaces have attracted much attention for their self-cleaning capabilities. It remains unclear how the versatile PDA adhesive would interact with slippery surfaces. In this work, both liquid-infused poly(tetrafluoroethylene) (PTFE) (LI-PTFE) and solid slippery surfaces (i.e., self-assembly of small thiol-terminated organosilane, polysiloxane covalently attached to substrates) were fabricated to investigate their capability to prevent PDA deposition. It was found that PDA particles could be easily deposited on a PTFE membrane and the two types of solid slippery surfaces, which resulted in the alternation of their surface wettability and slippery behavior of water droplets. Adhesion was detected between a PDA-coated silica colloidal probe and the PTFE membrane or solid slippery surfaces through quantitative force measurements using an atomic force microscope (AFM), mainly due to van der Waals (vdW) and hydrophobic interactions, which led to the PDA deposition phenomenon. In contrast, LI-PTFE with a thin liquid lubricant film could effectively prevent PDA deposition, with negligible changes in surface morphology, wettability, and slippery characteristics. Although PDA particles could be loosely attached to the lubricant/water interface for LI-PTFE based on the capillary adhesion measured by AFM, they could be readily removed by gentle rinsing with water, as demonstrated by the ultralow friction over LI-PTFE as compared to PTFE using lateral force microscopy (LFM). Our results indicate that LI-PTFE possesses excellent antifouling and self-cleaning properties even when interacting with the versatile PDA wet adhesives. This work provides new insights into the deposition of PDA on slippery surfaces and their interaction mechanism at the nanoscale, with useful implications for the design and development of novel slippery surfaces.

Direct measurement of individual optical forces in ensembles of trapped particles

Optical tweezers are a powerful tool to hold and manipulate particles on the microscale. The ability to measure tiny forces enables detailed investigations, e.g., of the mechanical properties of biological systems. Here we present a generally applicable method to simultaneously measure all components of the force applied to a specific particle in a trapped ensemble, or to a specific site of an extended object. This holographic force measurement relies on a detailed analysis of a single interference pattern formed in the far field to recover amplitude and phase of the field. It requires no information about size, shape, or optical properties of the particles and can be scaled to many traps—we show individual force measurements for up to 10 particles. In addition, we demonstrate force measurements when stretching a red blood cell, held directly by four traps. This method opens up a wealth of new opportunities made possible by localized quantitative force measurements in complex biological settings.

New instrument for quantitative measurements of passive duction forces and its clinical implications.

Evaluating the passive duction force of the extraocular muscles is important for the diagnosis of and surgical planning for strabismus. This is especially relevant in patients with an observable limitation of duction movement. The purpose of this study was to validate passive duction forces in healthy subjects using a novel instrument. An instrument for making continuous quantitative measurements of passive duction forces was designed. Tension was measured as the eyeball was rotated horizontally or vertically from the resting position under general anesthesia 10 mm (50°) away from the direction of force to be tested (opposite side). Seventy eyes of 35 subjects were enrolled in this study (age range of 4-80 years and mean age of 36.3 years). The passive duction force was measured at 49.0 ± 15.3 g (mean ± standard deviation) for medial rotation, 44.8 ± 13.2 g for lateral rotation, 50.5 ± 14.8 g for superior rotation, and 53.5 ± 13.8 g for inferior rotation. The passive duction forces were similar for all gaze positions, but it was larger for inferior rotation than for lateral rotation (P = 0.009). The passive duction force was significantly larger for vertical rotation (51.9 ± 14.4 g) than for horizontal rotation (46.9 ± 14.4 g) (P = 0.006). The passive duction force did not differ significantly with sex (P = 0.355), side (P = 0.087), or age (P = 0.872). These measurements of passive duction forces in a healthy population provide valuable information for diagnosing specific strabismic problems and could be useful for increasing the precision of strabismus surgery. Graphical abstract.

Calibration of T-shaped atomic force microscope cantilevers using the thermal noise method.

The tip-sample interaction force measurements in atomic force microscopy (AFM) provide information about materials' properties with nanoscale resolution. The T-shaped cantilevers used in Torsional-Harmonic AFM allow measuring the rapidly changing tip-sample interaction forces using the torsional (twisting) deflections of the cantilever due to the off-axis placement of the sharp tip. However, it has been difficult to calibrate these cantilevers using the commonly used thermal noise-based calibration method as the mechanical coupling between flexural and torsional deflections makes it challenging to determine the deflection sensitivities from force-distance curves. Here, we present thermal noise-based calibration of these T-shaped AFM cantilevers by simultaneously analyzing flexural and torsional thermal noise spectra, along with deflection signals during a force-distance curve measurement. The calibration steps remain identical to the conventional thermal noise method, but a computer performs additional calculations to account for mode coupling. We demonstrate the robustness of the calibration method by determining the sensitivity of calibration results to the laser spot position on the cantilever, to the orientation of the cantilever in the cantilever holder, and by repeated measurements. We validated the quantitative force measurements against the known unfolding force of a protein, the I91 domain of titin, which resulted in consistent unfolding force values among six independently calibrated cantilevers.

Quantitative electrostatic force measurement and characterization based on oscillation amplitude using atomic force microscopy

Measurement of electrostatic force at the micro-/nanoscale has a great scientific value and engineering significance. This paper develops a new determination method of electrostatic forces based on Kelvin probe force mode in atomic force microscopy (AFM). Applying DC voltage and AC voltage simultaneously, we measured the oscillation amplitudes of the probe at two specific frequencies. By the equivalent parallel-plate capacitor model and the vibration theory, we established quantitative relationship between electrostatic force and AFM raw data, and derived a complete and practical formula for calculating electrostatic force. Then, the fundamental characteristics of electrostatic force with time were revealed, and the changes of all components of electrostatic force with tip–sample distance and applied AC peak voltage were discussed in detail. The regulation effects of the distance and the voltage on the total electrostatic force were also compared. Furthermore, we pointed out the main advantages and disadvantages of this method and stated the applicable conditions of the conclusions according to the experimental results and theoretical analysis.

Design and Construction of A Continuous Quantitative Force Measurement Microdevice for Artificial Skeletal Muscle

Design and Construction of A Continuous Quantitative Force Measurement Microdevice for Artificial Skeletal Muscle