Editing Atomic force microscopy (section)

==Force spectroscopy==
Besides imaging, AFM can be used for [[force spectroscopy]], the direct measurement of tip-sample interaction forces as a function of the gap between the tip and sample. The result of this measurement is called a force-distance curve. For this method, the AFM tip is extended towards and retracted from the surface as the deflection of the cantilever is monitored as a function of [[Piezoelectricity|piezoelectric]] displacement. These measurements have been used to measure nanoscale contacts, [[Chemical bond|atomic bonding]], [[Van der Waals force]]s, and [[Casimir effect|Casimir forces]], [[Solvation|dissolution]] forces in liquids and single molecule stretching and rupture forces.<ref>{{cite journal|doi=10.1038/nmeth871|date=May 2006|author1=Hinterdorfer, P |author2=Dufrêne, Yf |title=Detection and localization of single molecular recognition events using atomic force microscopy|volume=3|issue=5|pages=347–55|issn=1548-7091|pmid=16628204|journal=[[Nature Methods]]|s2cid=8912697}}</ref> AFM has also been used to measure, in an aqueous environment, the dispersion force due to polymer adsorbed on the substrate.<ref>{{cite journal | last1 = Ferrari | first1 = L. | last2 = Kaufmann | first2 = J. | last3 = Winnefeld | first3 = F. | last4 = Plank | first4 = J. | date = Jul 2010 | title = Interaction of cement model systems with superplasticizers investigated by atomic force microscopy, zeta potential, and adsorption measurements | journal = [[J Colloid Interface Sci]] | volume = 347 | issue = 1| pages = 15–24 | doi=10.1016/j.jcis.2010.03.005 | pmid=20356605|bibcode = 2010JCIS..347...15F }}</ref> Forces of the order of a few [[piconewton]]s can now be routinely measured with a vertical distance resolution of better than 0.1 nanometers.  Force spectroscopy can be performed with either static or dynamic modes.  In dynamic modes, information about the cantilever vibration is monitored in addition to the static deflection.<ref>{{cite journal|doi=10.1016/j.surfrep.2005.08.003|year=2005|author1=Butt, H |author2=Cappella, B |author3=Kappl, M |title = Force measurements with the atomic force microscope: Technique, interpretation and applications|journal=Surface Science Reports|volume=59|issue=1|pages=1–152|bibcode = 2005SurSR..59....1B |citeseerx=10.1.1.459.3771}}</ref>

Problems with the technique include no direct measurement of the tip-sample separation and the common need for low-stiffness cantilevers, which tend to "snap" to the surface. These problems are not insurmountable.  An AFM that directly measures the tip-sample separation has been developed.<ref>{{cite journal|doi=10.1021/nl803298q|title=Ultrastable Atomic Force Microscopy: Atomic-Scale Stability and Registration in Ambient Conditions|year=2009|author1=Gavin M. King |author2=Ashley R. Carter |author3=Allison B. Churnside |author4=Louisa S. Eberle |author5=Thomas T. Perkins  |name-list-style=amp|journal=[[Nano Letters]]|volume=9|pages=1451–1456|bibcode = 2009NanoL...9.1451K|issue=4|pmid=19351191|pmc=2953871 }}</ref>  The snap-in can be reduced by measuring in liquids or by using stiffer cantilevers, but in the latter case a more sensitive deflection sensor is needed. By applying a small [[dither]] to the tip, the stiffness (force gradient) of the bond can be measured as well.<ref>{{cite journal|doi=10.1098/rspa.2000.0713|title=Direct measurement of interatomic force gradients using an ultra-low-amplitude atomic force microscope|year=2001|author1=Peter M. Hoffmann|author2= Ahmet Oral |author3=Ralph A. Grimble |journal=[[Proceedings of the Royal Society A]]|volume=457|pages=1161–1174|bibcode = 2001RSPSA.457.1161H|issue=2009 |citeseerx=10.1.1.487.4270|s2cid=96542419}}</ref>

===Biological applications and other===
[[Force spectroscopy]] is used in [[biophysics]] to measure the mechanical properties of living material (such as tissue or cells)<ref>{{cite journal|last=Radmacher|first=M.|title=Measuring the elastic properties of biological samples with the AFM|journal=IEEE Eng Med Biol Mag|year=1997|volume=16|issue=2|pages=47–57|doi=10.1109/51.582176|pmid=9086372}}</ref><ref>{{cite web|last1=Perkins|first1=Thomas|title=Atomic force microscopy measures properties of proteins and protein folding|url=http://spie.org/newsroom/technical-articles/videos/perkins-video-x116732|publisher=SPIE Newsroom|access-date=4 March 2016}}</ref><ref>{{cite journal|title=Single-cell unroofing: probing topology and nanomechanics of native membranes|doi=10.1016/j.bbamem.2018.09.019|pmid=30273580|year=2018|last1=Galvanetto|first1=Nicola|journal=Biochimica et Biophysica Acta (BBA) - Biomembranes|volume=1860|issue=12|pages=2532–2538|arxiv=1810.01643|s2cid=52897823}}</ref> or detect structures of different stiffness buried into the bulk of the sample using the stiffness tomography.<ref>{{cite journal | first1=Charles | last1=Roduit | last2=Sekatski | first2=Serguei | last3=Dietler | first3=Giovanni | last4=Catsicas | first4=Stefan | last5=Lafont | first5=Frank | last6=Kasas | first6=Sandor | title= Stiffness Tomography by Atomic Force Microscopy | journal=Biophysical Journal | volume=97 | issue=2 | date=2009 | pages=674–677 | doi=10.1016/j.bpj.2009.05.010| pmid=19619482 | pmc=2711326 | bibcode=2009BpJ....97..674R }}</ref> Another application was to measure the interaction forces between from one hand a material stuck on the tip of the cantilever, and from another hand the surface of particles either free or occupied by the same material. From the adhesion force distribution curve, a mean value of the forces has been derived. It allowed to make a cartography of the surface of the particles, covered or not by the material.<ref>{{cite journal|last=Thomas|first=G.|author2=Y. Ouabbas|author3=P. Grosseau |author4=M. Baron |author5=A. Chamayou |author6=L. Galet|title=Modeling the mean interaction forces between power particles. Application to silice gel-magnesium stearate mixtures|journal=Applied Surface Science|year=2009|volume=255|issue=17|pages=7500–7507|doi=10.1016/j.apsusc.2009.03.099|bibcode = 2009ApSS..255.7500T |citeseerx=10.1.1.591.1899|s2cid=39028440 }}</ref> AFM has also been used for mechanically unfolding proteins.<ref>{{cite journal|year=1997|author1=Rief, M |author2=Gautel, M |author3=Oesterhelt, F |author4=Fernandez, J M |author5=Gaub, H E |title = Reversible Unfolding of Individual Titin Immunoglobulin Domains by AFM |journal= Science |volume=276|issue=5315|pages=1109–1112|doi = 10.1126/science.276.5315.1109 |pmid=9148804 }}</ref> In such experiments, the analyzes of the mean unfolding forces with the appropriate model<ref>{{cite journal | last1 = Petrosyan | first1 = R. | year = 2020 | title = Unfolding force definition and the unified model for the mean unfolding force dependence on the loading rate | journal = J. Stat. Mech. | volume = 2020 | number = 33201 | page = 033201 | doi = 10.1088/1742-5468/ab6a05 | arxiv = 1904.03925 | bibcode = 2020JSMTE..03.3201P | doi-access = free }}</ref> leads to the obtainment of the information about the unfolding rate and free energy profile parameters of the protein.