active-probe-atomic-force-microscopy-with-quattro-parallel-cantilever

Active Probe Atomic Force Microscopy with Quattro-Parallel Cantilever Arrays for High-Throughput Large-Scale Sample Inspection

An Atomic Force Microscope&#160;(AFM) is&#160;a powerful and versatile tool for nanoscale surface studies to capture 3D topography images of samples. ...

Massachusetts Institute of Technology

High speed imaging and mapping of nanomechanical properties in atomic force microscopy (AFM) allows the observation and characterization of dynamic sample processes. Recent developments involve several cantilever frequencies in a multifrequency approach. One method actuates the first eigenmode for topography imaging and records the excited higher harmonics to map nanomechanical properties of the sample. To enhance the higher frequencies' response two or more eigenmodes are actuated simultaneously, where the higher eigenmode(s) are used to quantify the nanomechanics. In this paper, we combine each imaging methodology with a novel control approach. It modifies the Q factor and resonance frequency of each eigenmode independently to enhance the force sensitivity and imaging bandwidth. It allows us to satisfy the different requirements for the first and higher eigenmode. The presented compensator is compatible with existing AFMs and can be simply attached with minimal modifications. Different samples are used to demonstrate the improvement in nanomechanical contrast mapping and imaging speed of tapping mode AFM in air. The experiments indicate most enhanced nanomechanical contrast with low Q factors of the first and high Q factors of the higher eigenmode. In this scenario, the cantilever topography imaging rate can also be easily improved by a factor of 10.

Multi-eigenmode control for high material contrast in bimodal and higher harmonic atomic force microscopy.

The development of an accurate and reliable noninvasive near-infrared (NIR) glucose sensor hinges on the success in addressing the sensitivity and the specificity problems associated with the weak glucose signals and the overlapping NIR spectra. Spectroscopic hardware parameters most relevant to noninvasive blood glucose measurement are discussed, which include the optical throughput, integration time, spectral range, and the spectral resolution. We propose a unique spectroscopic system using a continuously rotating interference filter, which produces a signal-to-noise ratio of the order of 10(5) and is estimated to be the minimum required for successful in vivo glucose sensing. Using a classical least-squares algorithm and a spectral range between 2180 and 2312 nm, we extracted clinically relevant glucose concentrations in multicomponent solutions containing bovine serum albumin, triacetin, lactate, and urea.

Design of a mechanical-tunable filter spectrometer for noninvasive glucose measurement.

Cancer cells have distinctive electrochemical properties. This work sheds light on the system design aspects and key challenges that should be considered when experimentally analyzing and extracting the electrical characteristics of a tumor cell line. In this study, we developed a cellularbased functional microfabricated device using lithography technology. This device was used to investigate the electrochemical parameters of cultured cancer cells at the single-cell level. Using impedance spectroscopy analyses, we determined the average specific capacitance and resistance of the membrane of the cancer cell line B16-F10 to be 1.154 +/- 0.29 microF/cm(2), and 3.9 +/- 1.15 KOmega.cm(2) (mean +/- SEM, n =14 cells), respectively. The consistency of our findings via different trails manifests the legitimacy of our experimental procedure. Furthermore, the data were compared with a proposed constructed analytical-circuit model. The results of this work may greatly assist researchers in defining an optimal procedure while extracting electrical properties of cancer cells. Detecting electrical signals at the single cell level could lead to the development of novel approaches for analysis of malignant cells in human tissues and biopsies.

Extracting cancer cell line electrochemical parameters at the single cell level using a microfabricated device.

A special configuration of white-light scanning interferometer is described for measuring the absolute air gap thickness between two planar plates brought into close proximity. The measured gap is not located in any interference arm of the interferometer, but acts as an amplitude-and-phase modulator of the light source. Compared with the common white-light interferometer our approach avoids the influence of the chromatic dispersion of the planar plates on the gap thickness quantification. It covers a large measurement range of from approximate contact to tens of microns with a high resolution of 0.1 nm. Detailed analytical models are presented and signal-processing algorithms based on convolution and correlation techniques are developed. Practical measurements are carried out and the experimental results match well with the analysis and simulation. Short-time and long-time repeatabilities are both tested to prove the high performance of our method.

White-light scanning interferometer for absolute nano-scale gap thickness measurement.

A Moiré fringe approach is developed to identify simultaneously the global and local distortions in hot-embossed polymeric samples. A square grid pattern with a pitch of 63.5 microm is hot-embossed on the polymer substrate. When a reference grid, a polymeric film with the same pattern, is placed on top of the sample, a Moiré fringe pattern is observed and recorded by a document scanner. The deviation of the intersections of the fringes from their ideal positions presents the residual distortion in the sample. With different sample-reference rotation angles eight images are acquired for the same sample to achieve the optimal result by a data fitting technique. The validity of this method is proved by the self-consistency of the results from the eight images. To the best of our knowledge, this is the first time distortion quantification has been achieved both in a large area up to that of a scanner and with a high resolution at the level of 1 microm. Furthermore, we do not use any expensive instrument, nor need to measure the sample-reference rotation angle or position the sample precisely, and the process is run automatically by a computer instead of manual operation.

Large-area and high-resolution distortion measurement based on Moiré fringe method for hot embossing process.

Utilizing a newly developed atomic-force-microscopy-based wide-frequency rheology system, we measured the dynamic nanomechanical behavior of normal and glycosaminoglycan (GAG)-depleted cartilage, the latter representing matrix degradation that occurs at the earliest stages of osteoarthritis. We observed unique variations in the frequency-dependent stiffness and hydraulic permeability of cartilage in the 1Â Hz-to-10 kHz range, a frequency range that is relevant to joint motions from normal ambulation to high-frequency impact loading. Measurement in this frequency range is well beyond the capabilities of typical commercial atomic force microscopes. We showed that the dynamic modulus of cartilage undergoes a dramatic alteration after GAG loss, even with the collagen network still intact: whereas the magnitude of the dynamic modulus decreased two- to threefold at higher frequencies, the peak frequency of the phase angle of the modulus (representing fluid-solid frictional dissipation) increased 15-fold from 55Â Hz in normal cartilage to 800Â Hz after GAG depletion. These results, based on a fibril-reinforced poroelastic finite-element model, demonstrated that GAG loss caused a dramatic increase in cartilage hydraulic permeability (up to 25-fold), suggesting that early osteoarthritic cartilage is more vulnerable to higher loading rates than to the conventionally studied "loading magnitude". Thus, over the wide frequency range of joint motion during daily activities, hydraulic permeability appears the most sensitive marker of early tissue degradation.

High-Bandwidth AFM-Based Rheology Reveals that Cartilage is Most Sensitive to High Loading Rates at Early Stages of Impairment.

Utilisant un syst&egrave;me developp&eacute; r&eacute;cemment atomic force microscopy-dot&eacute;s d&#39;&eacute;chelle-fr&eacute;quence rh&eacute;ologie, nous avons mesur&eacute; le comportement dynamique nanom&eacute;triques de normale et de glycosaminoglycanes (GAG)-appauvri le cartilage, la d&eacute;gradation de matrice qui repr&eacute;sente cette derni&egrave;re qui se produit dans les premiers stades de l&#39;arthrose. Nous avons observ&eacute; des variations uniques dans la rigidit&eacute; d&eacute;pendant de la fr&eacute;quence et de la perm&eacute;abilit&eacute; hydraulique du cartilage dans la gamme de 1 Hz &agrave; 10 kHz, une bande passante qui s&#39;applique aux propositions communes de d&eacute;ambulation normale au chargement d&#39;impact haute-fr&eacute;quence. Mesure dans cette gamme de fr&eacute;quences est bien au del&agrave; que les fonctionnalit&eacute;s du commercial typique atomique force microscopes. Nous avons montr&eacute; que le module dynamique du cartilage subit une alt&eacute;ration dramatique apr&egrave;s perte GAG, m&ecirc;me avec le r&eacute;seau de collag&egrave;ne encore intacte : tandis que l&#39;ampleur du module dynamique diminue-de deux &agrave; trois fois &agrave; des fr&eacute;quences plus &eacute;lev&eacute;es, la fr&eacute;quence maximale de l&#39;angle de phase du module (repr&eacute;sentant la dissipation par frottement fluide-solide) a augment&eacute; de 15 fois de 55 Hz dans le cartilage normal &agrave; 800Hz apr&egrave;s &eacute;puisement de GAG. Ces r&eacute;sultats, bas&eacute;s sur un mod&egrave;le d&#39;&eacute;l&eacute;ments finis poro&eacute;lastique renforc&eacute;s de fibrilles, d&eacute;montr&eacute; que GAG perte a entra&icirc;n&eacute; une augmentation dramatique de perm&eacute;abilit&eacute; hydraulique du cartilage (jusqu&#39;&agrave; 25 fois), sugg&eacute;rant que le cartilage arthrose pr&eacute;coce est taux de chargement plus vuln&eacute;rables &agrave; la hausse qu&#39;&agrave; la fa&ccedil;on conventionnelle &eacute;tudi&eacute;e &laquo; chargement grandeur &raquo;. Ainsi, au cours de la large bande passante d&#39;une proposition commune au cours d&#39;activit&eacute;s quotidiennes, perm&eacute;abilit&eacute; hydraulique semble le marqueur le plus sensible de d&eacute;gradation pr&eacute;coce des tissus.

Rh&eacute;ologie de haut-bande passante AFM-Based r&eacute;v&egrave;le que le Cartilage est plus sensible &agrave; des taux &eacute;lev&eacute;s de chargement &agrave; des stades pr&eacute;coces de la d&eacute;ficience.

Utilizzando un sistema di nuova concezione atomica-forza-microscopia-basato-frequenze reologia, abbiamo misurato il comportamento dinamico nanomeccanici del normale e glicosaminoglicano (GAG)-impoverito della cartilagine, il degrado di matrix che rappresenta quest&#39;ultima che si verifica alle prime fasi dell&#39;artrosi. Abbiamo osservato uniche variazioni nella frequenza dipendente rigidit&agrave; e permeabilit&agrave; idraulica della cartilagine nella gamma di 1 Hz a 10 kHz, una gamma di frequenza che &egrave; pertinente alle proposte congiunte da normale deambulazione a impatto ad alta frequenza di caricamento. Misura in questa gamma di frequenza &egrave; ben oltre che le funzionalit&agrave; del tipico commerciale atomic force microscopi. Abbiamo dimostrato che il modulo dinamico della cartilagine subisce un&#39;alterazione drammatica dopo la perdita di GAG, anche con la rete di collagene intatta: mentre la grandezza del modulo dinamico sono diminuiti due-a triplice a frequenze pi&ugrave; alte, la frequenza di picco dell&#39;angolo di fase del modulo (che rappresenta la dissipazione d&#39;attrito del fluido-solido) aumentato di 15 volte da 55 Hz in normale cartilagine a 800 Hz dopo esaurimento GAG. Questi risultati, basati su un modello di elementi finiti poroelastic rinforzata fibrillare, hanno dimostrato che la perdita GAG causate un drammatico aumento della permeabilit&agrave; idraulica della cartilagine (fino a ghiacciamento), suggerendo che la cartilagine osteoartritiche precoce &egrave; pi&ugrave; vulnerabili ai pi&ugrave; alti tassi di caricamento rispetto a convenzionalmente studiato &quot;caricamento di grandezza&quot;. Cos&igrave;, oltre la gamma di frequenza ampia di movimento congiunto durante le attivit&agrave; quotidiane, permeabilit&agrave; idraulica appare l&#39;indicatore pi&ugrave; sensibile della precoce degradazione dei tessuti.

Reologia basati su High-Bandwidth AFM rivela che la cartilagine &egrave; pi&ugrave; sensibile ad alti tassi di carico alle prime fasi di svalutazione.

Poroelastic interactions between interstitial fluid and the extracellular matrix of connective tissues are critical to biological and pathophysiological functions involving solute transport, energy dissipation, self-stiffening and lubrication. However, the molecular origins of poroelasticity at the nanoscale are largely unknown. Here, the broad-spectrum dynamic nanomechanical behavior of cartilage aggrecan monolayer is revealed for the first time, including the equilibrium and instantaneous moduli and the peak in the phase angle of the complex modulus. By performing a length scale study and comparing the experimental results to theoretical predictions, we confirm that the mechanism underlying the observed dynamic nanomechanics is due to solid-fluid interactions (poroelasticity) at the molecular scale. Utilizing finite element modeling, the molecular-scale hydraulic permeability of the aggrecan assembly was quantified (kaggrecan = (4.8 ± 2.8) × 10(-15) m(4)/N·s) and found to be similar to the nanoscale hydraulic permeability of intact normal cartilage tissue but much lower than that of early diseased tissue. The mechanisms underlying aggrecan poroelasticity were further investigated by altering electrostatic interactions between the molecule's constituent glycosaminoglycan chains: electrostatic interactions dominated steric interactions in governing molecular behavior. While the hydraulic permeability of aggrecan layers does not change across species and age, aggrecan from adult human cartilage is stiffer than the aggrecan from newborn human tissue.

Aggrecan nanoscale solid-fluid interactions are a primary determinant of cartilage dynamic mechanical properties.

Owing to recent climate changes, dust storms are increasingly common, particularly in the Middle East region. Dust accumulation and subsequent mud formation on solid surfaces in humid environments typically have adverse effects on surface properties such as optical transmittance, surface texture, and microhardness. This is usually because the mud, which contains alkaline and ionic species, adheres strongly to the surface, often through chemical bonds, and is therefore difficult to remove. In this study, environmental dust and the after-effects of mud formed on a polycarbonate sheet, which is commonly used as a protective glass in photovoltaic cells. Ionic compounds (OH(-)) are shown to significantly affect the optical, mechanical, and textural characteristics of the polycarbonate surface, and to increase the adhesion work required to remove the dry mud from the polycarbonate surface upon drying. Such ability to modify characteristics of the polycarbonate surface could address the dust/mud-related limitations of superhydrophobic surfaces.

Characterization of Environmental Dust in the Dammam Area and Mud After-Effects on Bisphenol-A Polycarbonate Sheets.

This paper proposes a gossip-based protocol that utilises a multi-factor weighting function (MFWF) that takes several parameters into account: residual energy, Chebyshev distances to neighbouring nodes and the sink node, node density, and message priority. The effects of these parameters were examined to guide the customization of the weight function to effectively disseminate data to three types of IoT applications: critical, bandwidth-intensive, and energy-efficient applications. The performances of the three resulting MFWFs were assessed in comparison with the performances of the traditional gossiping protocol and the Fair Efficient Location-based Gossiping (FELGossiping) protocol in terms of end-to-end delay, network lifetime, rebroadcast nodes, and saved rebroadcasts. The experimental results demonstrated the proposed protocol's ability to achieve a much shorter delay for critical IoT applications. For bandwidth-intensive IoT application, the proposed protocol was able to achieve a smaller percentage of rebroadcast nodes and an increased percentage of saved rebroadcasts, i.e., better bandwidth utilisation. The adapted MFWF for energy-efficient IoT application was able to improve the network lifetime compared to that of gossiping and FELGossiping. These results demonstrate the high level of flexibility of the proposed protocol with respect to network context and message priority.

Context-Aware Gossip-Based Protocol for Internet of Things Applications.

Slippery and hydrophilic surfaces find critical applications in areas as diverse as biomedical devices, microfluidics, antifouling, and underwater robots. Existing methods to achieve such surfaces rely mostly on grafting hydrophilic polymer brushes or coating hydrogel layers, but these methods suffer from several limitations. Grafted polymer brushes are prone to damage and do not provide sufficient mechanical compliance due to their nanometer-scale thickness. Hydrogel coatings are applicable only for relatively simple geometries, precluding their use for the surfaces with complex geometries and features. Here, a new method is proposed to interpenetrate hydrophilic polymers into the surface of diverse polymers with arbitrary shapes to form naturally integrated "hydrogel skins." The hydrogel skins exhibit tissue-like softness (Young's modulus ≈ 30 kPa), have uniform and tunable thickness in the range of 5-25 µm, and can withstand prolonged shearing forces with no measurable damage. The hydrogel skins also provide superior low-friction, antifouling, and ionically conductive surfaces to the polymer substrates without compromising their original mechanical properties and geometry. Applications of the hydrogel skins on inner and outer surfaces of various practical polymer devices including medical tubing, Foley catheters, cardiac pacemaker leads, and soft robots on massive scales are further demonstrated.

Multifunctional "Hydrogel Skins" on Diverse Polymers with Arbitrary Shapes.

Atomic force microscopy is a powerful topography imaging method used widely in nanoscale metrology and manipulation. A conventional Atomic Force Microscope (AFM) utilizes an optical lever system typically composed of a laser source, lenses and a four quadrant photodetector to amplify and measure the deflection of the cantilever probe. This optical method for deflection sensing limits the capability of AFM to obtaining images in transparent environments only. In addition, tapping mode imaging in liquid environments with transparent sample chamber can be difficult for laser-probe alignment due to multiple different refraction indices of materials. Spurious structure resonance can be excited from piezo actuator excitation. Photothermal actuation resolves the resonance confusion but makes optical setup more complicated. In this paper, we present the design and fabrication method of coated active scanning probes with piezoresistive deflection sensing, thermomechanical actuation and thin photoresist polymer surface coating. The newly developed probes are capable of conducting topography imaging in opaque liquids without the need of an optical system. The selected coating can withstand harsh chemical environments with high acidity (e.g., 35% sulfuric acid). The probes are operated in various opaque liquid environments with a custom designed AFM system to demonstrate the imaging performance. The development of coated active probes opens up possibilities for observing samples in their native environments.

Lights Out! Nano-Scale Topography Imaging of Sample Surface in Opaque Liquid Environments with Coated Active Cantilever Probes.

The spontaneous formation of biological substances, such as human organs, are governed by different stimuli driven by complex 3D self-organization protocols at the molecular level. The fundamentals of such molecular self-assembly processes are critical for fabrication of advanced technological components in nature. We propose and experimentally demonstrate a promising 3D printing method with self-healing property based on molecular self-assembly-monolayer principles, which is conceptually different than the existing 3D printing protocols. The proposed molecular building-block approach uses metal ion-mediated continuous self-assembly of organic molecular at liquid-liquid interfaces to create 2D and 3D structures. Using this technique, we directly printed nanosheets and 3D rods using dithiol molecules as building block units.

Building block 3D printing based on molecular self-assembly monolayer with self-healing properties.

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.

Article	Year
Multi-eigenmode control for high material contrast in bimodal and higher harmonic atomic force microscopy. Nanotechnology\| PubMed ID: 25994333	2015
Design of a mechanical-tunable filter spectrometer for noninvasive glucose measurement. Applied optics\| PubMed ID: 15130007	2004
Extracting cancer cell line electrochemical parameters at the single cell level using a microfabricated device. Biotechnology journal\| PubMed ID: 19226555	2009
White-light scanning interferometer for absolute nano-scale gap thickness measurement. Optics express\| PubMed ID: 19687988	2009
Large-area and high-resolution distortion measurement based on Moiré fringe method for hot embossing process. Optics express\| PubMed ID: 20372570	2009
High-Bandwidth AFM-Based Rheology Reveals that Cartilage is Most Sensitive to High Loading Rates at Early Stages of Impairment. Biophysical journal\| PubMed ID: 23561529	2013
Aggrecan nanoscale solid-fluid interactions are a primary determinant of cartilage dynamic mechanical properties. ACS nano\| PubMed ID: 25758717	2015
Characterization of Environmental Dust in the Dammam Area and Mud After-Effects on Bisphenol-A Polycarbonate Sheets. Scientific reports\| PubMed ID: 27076199	2016
Context-Aware Gossip-Based Protocol for Internet of Things Applications. Sensors (Basel, Switzerland)\| PubMed ID: 29997354	2018
Multifunctional "Hydrogel Skins" on Diverse Polymers with Arbitrary Shapes. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 30570776	2019
Lights Out! Nano-Scale Topography Imaging of Sample Surface in Opaque Liquid Environments with Coated Active Cantilever Probes. Nanomaterials (Basel, Switzerland)\| PubMed ID: 31337145
Building block 3D printing based on molecular self-assembly monolayer with self-healing properties. Scientific reports\| PubMed ID: 35474113	2022
Review: Advanced Atomic Force Microscopy Modes for Biomedical Research. Biosensors\| PubMed ID: 36551083	2022

Kamal Youcef-Toumi

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