Delft University of Technology
Imaging modes of atomic force microscopy for application in molecular and cell biology
Dufrêne, Yves F.; Ando, Toshio; Garcia, Ricardo; Alsteens, David; Martinez-Martin, David; Engel, Andreas;
Gerber, Christoph; Müller, Daniel J.
DOI
10.1038/nnano.2017.45
Publication date
2017
Document Version
Accepted author manuscript
Published in
Nature Nanotechnology
Citation (APA)
Dufrêne, Y. F., Ando, T., Garcia, R., Alsteens, D., Martinez-Martin, D., Engel, A., Gerber, C., & Müller, D. J.
(2017). Imaging modes of atomic force microscopy for application in molecular and cell biology.
Nature
Nanotechnology
,
12
(4), 295-307. https://doi.org/10.1038/nnano.2017.45
Important note
To cite this publication, please use the final published version (if applicable).
Please check the document version above.
Copyright
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent
of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
Takedown policy
Please contact us and provide details if you believe this document breaches copyrights.
We will remove access to the work immediately and investigate your claim.
This work is downloaded from Delft University of Technology.
For technical reasons the number of authors shown on this cover page is limited to a maximum of 10.
! !
Review&article&for&Nature&Nanotechnology&
!
"#$%&'!($)'*!+&')$,'$-.!/%01&21!+$304&#&*,!
&2!+$4*'540)!023!6*44!7&$4$1.!
!
!"#$%&'%()*+,-#
.
/0%12$342%5-62
7
0%849:+62%;:+94:
<
0%(:"46%5=$>##-$
.
0%(:" 46%?:+>4-#@A?:+>4-
B
0%
5-6+#:$%C-D#=
E
0%F3+4$>2G3%;#+H#+
I
%:-6%(:-4#=%J'%?K==#+
B
/%
%
.
L-$>4>)>#% 2*% M4*#% N94#-9#$% :-6% O:==22-% CP9#==#-9#% 4-% M4*#% $94#-9#$% :-6% Q42>#93-2=2DR%
SOCMQLTU0%V-4"#+$4>W%9:>32=4X)#%6#%M2)":4-0%F+24P%6)%N)6%BAE0%H>#%MY'ZY'ZI'0%QA.<B[%M2)":4-A
=:A\#)"#0%Q#=D4)]'%
7
(#G:+>]#->%2*%^3R$49$0%_:-:@:`:%V-4"#+$4>R0%_:-:@:`:%a7ZA..a70%J:G:-'%
<
L-$>4>)>2%6#%F4#-94:%6#%?:>#+4:=#$%6#%?:6+460%FNLF0%N2+%J):-:%L-W$%6#%=:%F+)@%<0%7[ZBa%
?:6+460%NG:4-'!
B
(#G:+>]#->%2*%Q42$R$>#]$%N94#-9#%:-6%C-D4-##+4-D0%C46D#-b$$4$93#%1#93-4$93#%c293$93)=#%
SC1cU%dK+4930%?:>>#-$>+:$$#%7[0%BZEI%Q:$#=0%N`4>@#+=:-6'!
E
(#G:+>]#->%2*%Q42\:-2$94#-9#0%(#=*>%V-4"#+$4>R%2*%1#93-2=2DR0%e:-%6#+%O::=$`#D%[0%7I7[%
Fc%(#=*>0%13#%\#>3#+=:-6$'%
I
N`4$$%\:-2$94#-9#%L-$>4>)>#0%V-4"#+$4>R%2*%Q:$#=0%_=4-D#=H#+D$>+:$$#%[Z0%BZEY%Q:$#=0%
N`4>@#+=:-6'!
/#A]:4=f%R"#$'6)*+#-#g)9=2)":4-'H#h%6:-4#='])#==#+gH$$#'#>3@'93%
!
7%
!
!
"8,#)0'#!
O4>34-% >3+##% 6#9:6#$0% :>2]49% *2+9#% ]49+2$92GR % S5&?U% 3:$% H#92]#% :% G2`#+*)=%
])=>4*)-9>42-:=%4]:D4-D%G=:>*2+]0%#-:H=4-D%>3#%"4 $):=4@:>42-%:-6%]:-4G)=:>42-%2*%H42=2D49:=%
$:]G=#$0%*+2]% $4-D=#%]2=#9)=#$%>2%=4"4-D%9#==$'%N22-%:*>#+%4>$%4-"#->42-0%4>%`:$%+#92D-4@#6%>3:>%
>3#% *)==% G2>#->4:=% 2*% 5&?% 4]:D4-D% 4-% H42=2DR% +#X)4+#$% i#R% >#93-2=2D49:=% 6#"#=2G]#->$% 4-%
2+6#+%>2%$2="#%:%-)]H#+%2*%=4]4>:>42-$%:-6%6+:`H:9i$'% 134$%-##6%3:$%H##-%:%i#R%6+4"4-D%*2+9#%
>2`:+6$%6#"#=2G4-D%-#`%4]:D4-D%]26:=4>4#$0%G)$34-D%92->4-)2)$=R%>3#%*4#=6%:3#:6'%c#+#0%`#%
$)+"#R%>3#%H:$49%G+4-94G=#$0%:6":->:D#$%:-6%=4]4>:>42-$%2 *%>3#%]2$>%92]]2-%5&?%H424]:D4-D%
]26:=4>4#$%:":4=:H=#%>26:R0%$>:+>4-D%*+2]%>3#%G2G)=:+%92->:9>%:-6%6R-:]49%]26#$0%>2%-#`=R%
6#"#=2G#6% ]26#$0% 4-9=)64-D% ])=>4G:+:]#>+490% ]2=#9)=:+% +#92D-4>42-0% ])=>4*+#X)#-9R% :-6%
34D3A$G##6% 4]:D4-D'%O#% 64$9)$$%+#9#->% #P:]G=#$% >3:>%34D3=4D 3>% >3#% )-4X)#% 9:G:H4=4>4#$% 2*%
>3#$#%#]#+D4-D%-#`%]26:=4>4#$'%O#%:->494G:>#%>3:>0%4-%>3#%-#P>%6#9:6#0%>3#$#%-:-2>22=$%`4==%
3:"#% :% G+2*2)-6% 4-*=)#-9#% 2-% >3#% `:R% +#$#:+93#+$% =22i% :>% H42=2D49:=% $R$>#]$0% >3#+#HR%
3#=G4-D% >3#]% >2% $2="#% *)-6:]#->:=% X)#$>42-$% >3:>% 92)=6% -2>% 3:"#% H##-% :66+#$$#6% `4>3%
>+:64>42-:=%>#93-4X)#$'%
<%
!
!
/2#)$35'#&$2!
13#%#]#+D#-9#%2*%:>2]49%*2+9#%]49+2$92GR%S5&?U%<Z%R#:+$%:D2
.
%4-%>3#%>3#-%*=#6D=4-D%*4#=6%2*%
-:-2>#93-2=2DR
7
%3:$%2G#-#6%-#`%:"#-)#$%4-%G3R$49$0%93#]4$>+R0%H42=2DR0%:-6%]#6494-#0%:-6%
$4-9#%>3#-%3:$%92->4-)2)$=R%4-$G4+#6%+#$#:+93#+$%:==%2"#+%>3#%`2+=60%:$%>#$>4*4#6%HR%]2+#%>3:-%
<BZ0ZZZ%$94#->4*49%:+>49=#$%4-%G##+%+#"4#`#6%j2)+-:=$%S`#H%2*%$94#-9#U'%13#%i#R%4-"#->42-%`:$%
>2%92->2)+%-2-92-6)9>4"#%$)+*:9#$%])93%H#=2`%>3#%64 **+:9>42-%=4]4 >%2*%=4 D3>% HR%92->+2==4-D%:%
92-D=2]#+:>#%2*%*2+9#$%:9>4-D%H#>`##-%:%>4-R%G+2H#%:-6%>3#%2Hj#9>'%O3#+#:$%*4+$>%+#$)=>$%2-%
>3#% :>2]49% $9:=#% `#+#% 2H>:4-#6% `4>34-% :% R#:+
<
0% 4>% > 22i% :-2>3#+% *#`% R#:+$% >2% :992]G=4$3%
:>2]49%4]:D4-D%2*%-2- 92-6)9>4"#%$)+*:9#$%4- %":9))]'%?#:-`34=#0% >3#%>#93-4X)#%$ >:+>#6%>2%
H#%:6:G>#6%>2%`2+i%2"#+%:%" :$>%>#]G#+:>)+#%$9:=#%:-6%H:$49:==R%4-%#"#+R%#-"4+2-]#->
70B0E0I
'%
13#% :H4=4>R% >2% 4-"#$>4D:>#% $)+*:9#$% `4>3% #P9#G>42-:=%$4 D-:=A>2A-24$#% +:>42% :>%$)HA-:-2]#>#+%
+#$2=)>42-%>+4DD#+#6%:%`#:=>3%2*%5&?A+#=:>#6%>#93-4X)#$%)$4-D%:%":+4#>R%2*%G+2H#$%>2%=29:==R%
$#-$#% 4->#+:9>42-$% :-6% ]:-4G)=:>#% ]:>>#+% *+2]% >3#% :>2]49% >2% ] 49+2$92G49% $9:=#
70Y
'% 134$%
)-4X)#% *=#P4H4=4>R% 2*% 5&?% >2% 4]:D#0% G+2H#% :-6% ]:-4G)=:>#% ]:>#+4:=$% ]:6#% 4>% >3#% ]2$>%
"#+$:>4=#%>22=i4>%4-%-:-2$94#-9#%:-6%A>#93-2=2DR0% 93:-D#6% 2)+%G#+9#G>42-%2*%3:+6% :-6% $2*>%
]:>>#+% :-6% $>4])=:>#6% +#"2=)>42-:+R% 64$92"#+4#$% :-6% >#93-2=2D4#$
7
'% 13#% G2$$4H4=4>R% >2%
2G#+:>#%4-%*=)4649%#-"4+2-]#->$%:-6%:>%:]H4#->%>#]G#+:>)+#%]2"#6%5&?%>2`:+6$%H42=2DR0%
2G#-4-D% >3#% 622+% >2% 4]:D#% :-6% G+2H#% ]2=#9)=#$% :-6% 9#==$% :>% S$)HAU-:-2]#>#+%
+#$2=)>42-
B0E0I0[0a
'%12%:66+#$$%>3#%`46#%92]G=#P4>R%2*%H42=2D49:=%$R$>#]$0%+:-D4-D%*+2]%=4G46$0%
-)9=#49%:946$0%G+2>#4-$0%:$$#]H=4#$%>3#+#2*0%>2%9#==$%:-6%>4$$)#$0%:%`#:= >3%2*%5&?%]26:=4>4#$%
3:"#%H##-%6#"#=2G#6%2"#+%>3#%R#:+$%S(&19!:U'%?:j2+%:6":-9#$%4-%34D3A+#$2=)>42-%4]:D4-D%3:"#%
:=$2%H##-%:934#"#6%4-%92]G=#]#->:+R%]#>326$%4-9=)64-D%$)G#+%+#$2=)>42-%]49+2$92GR%:-6%
9+R2A#=#9>+2-% ]49+2$92GR0% `3493% $4D-4*49:->=R% #-+493%>3#% 4]:D4-D%>22=H2P% -2`% :":4=:H=#% >2%
]2=#9)=:+%:-6%9#==%H42=2DR%S;084*!:U'%%
?:-R%+#"4#`$%3:"#%H##-%G)H=4$3#6%4-% >3#% G:$>%>`2% 6#9:6#$%>3:>%6#$9+4H#%>3#%)$#%2*%9#+>:4-%
5&?% 4]:D4-D% ]26:=4>4#$% >2% 93:+:9>#+4@#% H42=2D49:=% $R$>#]$'% c2`#"#+0% :$% 4>% 4$% 64**49)=>% *2+%
-#`92]#+$%:-6%2*>#-%#"#-%*2+%:6":-9#6%)$#+$%>2%2"#+"4#`%>3#%G+4-94G=#$%2*%>3#$#%X)49i=R%
6#"#=2G4-D% :-6% 64"#+$#% 4]:D4-D%]26:=4>4#$% :-6% >2% #" := ):>#% >3#4+% :GG=4 9:H4=4>R0% :6":->:D#$%
:-6%=4]4>:>42-$0%`#%3#+#%$)+"#R%>3#%]2$>%$4D-4*49:->%$>#G$%>3:>%3:"#%=#6%>2%#$>:H=4$3%5&?%:$%:%
G2`#+*)=%>22=H2P%4-%]2=#9)=:+%:-6%9#==%H42=2DR'%O#%2)>=4-#%*2+%#:93%5&?%4]:D4-D%]26:=4>R%
>2%`3493%i4-6%2*%H4 2=2D4 9:=% $R$>#]$%4>%9:-%H#%G+#*#+:H=R%:GG=4#60%>3#4+%9)++#->%=4]4>:>42-$%:-6%
*)>)+#%G#+$G#9>4"#$'%%
!
"!<$5)2*.!&2#$!"(+!&%01&21!#*'=2&>5*,!
/%01&21!20#&?*!8&$4$1&'04!,.,#*%,!&2!4&>5&3!
13#% i#R% H+#:i>3+2)D3% >3:>% =#6% >2% H42=2D49:=% 5&?% `:$% >3#% 6#"#=2G]#->% 2*% :-% 2G>49:=%
6#>#9>42-% $R$>#]0% *2==2`#6% HR% >3#% 6#$4D-% 2*% :% *=)46% 93:]H#+0% #-:H=4-D% 4]:D4-D% 4-% H)**#+%
$2=)>42-% :-6% >3)$% ]:4->:4-4-D% >3#% -:>4"#% $>:>#% 2*% >3#% H42=2D49:=% $R$>#]
B0E
'% 13#% *4+$>% 5&?%
4]:D4-D% ]26#% 4-"#->#60%contact&mode0%+:$>#+%$9:-$%:%>4G%2"#+%>3#%$:]G=#%:-6%:6j)$>$%G4P#=A
HRAG4P#=% >3#% 3#4D3>% 2*% >3#% >4G% $2% >3:>% >3#% *2+9#% :GG=4#6% >2% >3#% $:]G=#% 4 $% i#G>% 92-$>:->%
S(&19!@0U'%13#%+#$)=>4-D%3#4D3>%4]:D#%+#$#]H=#$%>3#% $:]G=#%>2G2D+:G3R%`4>3%>3#%+#$2=)>42-%
6#G#-64-D%2-%>3#%+:64)$%2*%>3#%>4G0%>3#%$:]G=#%92++)D:>42-0%>3#%G3R$49:=%G+2G#+>4#$%2*%>3#%
$:]G=#0% :-6% 32`% G+#94$#=R% >3#% *##6H:9i% $R$>#]% 92->2)+$% >3#% >4G% 2"#+% >3#% $2*>% H42=2D49:=%
B%
!
!
$:]G=#'%%
N32+>=R%:*>#+%4->+26) 94-D%>3#%*4+$>%92]]#+94:==R%:":4=:H=#%5&?0%H42=2D49:=%$G#94]#-$%4]:D#6%
4-9=)6#6% :-4]:=% 9#==$
.Z0..
0% 9#==% ]#]H+:-#%G:>93#$% :-6%]#]H+:-#%G+2>#4-$
.70.<0.B
0% (\5% :-6%
8\5
.E
0% :$% `#==% :$% =4G46% *4=]$
.I0.Y
'% &2+% *=:>0% $]22>3=R% 92++)D:>#6% $)+*:9#$% $)93% :$% G+2>#4-$%
G+2>+)64-D% k.%-]% *+2]% ]#]H+:-#$% 92->:9>% ]26#% 5&?% 9:-% G+2"46#% >2G2D+:G3$% 2*% $4-D=#%
]#]H+:-#% G+2>#4-$% :>% =:>#+:=% :-6% "#+>49:=% +#$2=)>42-% 2*% l.%-]% :-6% lZ'.%-]0% +#$G#9>4"#=R%
S(&19!@8U
.B0.[0.a
'%134$%#P9#G>42-:==R%34D3%+#$2=)>42-%:-6%$4D-:=A>2A-24$#%+:>42%2*%5&?%:==2`#6%*2+%
#P:]G=#%>2%)-+:"#=%>3#%*)-9>42-:==R%+#=#":->%2=4D2]#+49%$>:>#%2*%":+42)$%`:>#+A$2=)H=#%:-6%
]#]H+:-#%G+2>#4-$
7Z07.07707<07B
'%TG#+:>#6%4-%>3#%>4]#A=:G$#%92->:9>%]26#%5&?%"4$):=4@#6%>3#%
]2+G32=2D49:=% 6R-:]49$% 2*% 9#==$
.Z0..
0% >3#% D+2`>3% 2*% G:>32=2D49:=% :]R=246% *4H+4=$
7E
0% >3#%
#-@R]:>49%6#D+:6:>42-%2*%(\5
7I
%2+%=4G46%]#]H+:-#$
7Y
0%:-6%G+2"46#6%4-$4D3>%4->2%>3#%`2+i4-D%
G+4-94G=#$% 2*% H:9> #+4:=% 2)>#+% ]#]H+:-#% G2+#$
7[
0% D:G% j)-9>42-$% #-:H=4-D% 4->#+9#==)=:+%
92--#9>42-$% H#>`##-% 9#+>:4-% :-4]:=% 9#==$
7a
% :-6% -)9=#:+% G2+#% 92]G=#P#$
<Z
'% T>3#+% #P94>4-D%
#P:]G=#$% ]2-4>2+#6% >3#% 4-$#+>42-% 2*% G:>32=2D49:=% >2P4-$% 4->2% ]#]H+:-#$
<.
% :-6% >3#%
$)G+:]2=#9)=:+%:+934>#9>)+#%2*%G32>2$R->3#>49%]#]H+:-#$%93:-D4-D%4-%+#$G2-$#%>2%=4D3>
<7
'%
N)93% 4-$4D3>% :==2`#6% $>:>49% $>+)9>)+:=% ]26#=$% >2% H#% 92]G=#]#->#6% `4>3% *)-9>42-:=%
6R-:]49$
<<
'%
5=>32)D3%92->:9>%]26#%5&?%4$%`46#=R%)$#6%>2%93:+:9>#+4@#%$2=46%$)H$>+:>#$0%4>$%:GG=49:>42-%>2%
$2*>%H42=2D49:=%$R$>#]$%+#X)4+#$%#PG#+>%$i4==$%>2%:6j)$>%>3#%*2+9#%:GG=4#6%>2%>3#%>4G'%5$%:%+)=#%2*%
>3)]H0%*2+9#$%m.ZZ%G\%$32)=6%H#%:"246#6%:$%>3#R%9:-%9:)$#%+#"#+$4H=#%2+%#"#-%4++#"#+$4H=#%
6#*2+]:>42-$
<<
'%Dynamic&mode&imaging%S2+4D4-:==R%>#+]#6%>:GG4-D%2+%2$94==:>42-%]26#U%`:$%
4-"#->#6%>2%]4-4]4@#%>3#%*+49>42-%:-6%>3#%* 2+9#%:GG=4#6%H#>`##-%>4G%:-6%$:]G=#%S(&19!@0A'U'%L-%
4>$% $4]G=#$>%:GG=49:>42-0% >3#%9:->4=#"#+%4$% 2$94==:>#6%9=2$#%>2%+#$2-:-9#%`34=#%$9:--4-D%:9+2$$%
:% $:]G=#
.
'% L6#:==R% >3#% >4G% 2-=R% >2)93#$% >3#% $:]G=#% :>% >3#% "#+R% #-6% 2*% 4>$% 62`-`:+6%
]2"#]#->%>3)$%92-$46#+:H=R%]4-4]4@4-D%*+49>42-'%L-%9=2$#%G+2P4]4>R%>2%>3#%$:]G=#% $)+*:9#0%
>3#% 4->#+:9>42-$% H#>`##-% >4G% :-6% $:]G=#% 93:-D#% H2>3% >3#% 9:->4=#"#+% :]G=4>)6#% :-6%
+#$2-:-9#% *+#X)#-9R% :==2`4-D% >3#]% >2% H#% )$#6% :$% *##6H:9i% G:+:]#>#+$% *2+% 92->2)+4-D%
*+:D4=#% H42=2D49: =% $:]G=#$
<B0<E0<I
'% V$4-D% >3#% :]G=4>)6#% :$% *##6H:9i% 4$% >#93-49:==R% $4]G=#+%
H#9:)$#% 4>% +#X)4+#$% 2-=R% 2-#% *##6H:9i% =22G% 92]G:+#6% >2% )$4-D% *+#X)#-9R% :$% *##6H:9i%
+#X)4+4-D%>3+##%$)93%=22G$'%13)$0%:]G=4>)6#%]26)=:>42-%5&?%4$%9)++#->=R%]2+#%2*>#-%:GG=4#6%
>3:-%*+#X)#-9R%]26)=:>42-%5&?'%Q#$46#$%>3#$#%>`2%`#== Ai-2`-%5&?%4]:D4-D%]26#$0%2>3#+%
6R-:]49% ]26#$% 3:"#% H##-% 6#"#=2G#6% `3493% #]G=2R% 64**#+#->% $4D-:=$% :$% *##6H:9i%
G:+:]#>#+$% 2+% #P94>#% >3#% 9:->4=#"#+% :>% 64**#+#->% *+#X)#-94#$% $4])=>:-#2)$=R% S$##% $#9>42-%
?)=>4*+#X)#-9R% L ]:D4-DU
<Y
'% L]G2+>:->=R0% :$% 6R-:]49% ]26#$% 92-$46#+:H=R% +#6)9#% *2+9#% :-6%
*+49>42-%H#>`##-%>4G%:-6%$:]G=#0%>3#R%9:-%H#%:GG=4#6%>2%4]:D#%H42=2D49:=%2Hj#9>$0%`3493%:+#%
2-=R%`#:i=R%:6$2+H#6%>2%$)GG2+>$0%=4i#%(\50%$4-D=#%G+2>#4-$0%:-6%*4=:]#->$
<[0<a0BZ0B.
'% (R-:]49%
]26#$% :=$2% :==2`% 34D3=R% 92++)D:>#6% 2Hj#9>$0% =4i#% =4"4-D% 9#==$0% >2% H#% 6#G49>#6% 4-% >3#4+%
)-G#+>)+H#6%$>:>#
B7
'%c2`#"#+0%>3#%>2G2D+:G349%92->+:$>%+#=4#$%2-%+:>3#+%92]G=#P%4->#+:9>42-%
]#93:-4$]$% H#>`##-% >3#% 5&?% >4G% :-6% $:]G=#'% N>4**-#$$0% +2)D3-#$$0% $)+*:9#% 93:+D#% :-6%
93#]4$>+R0%2+%*+49>42-%2*%>3#%$:]G=#%9:-%93:-D#% >3#% 2$94==:>42-%2*%>3#%>4G%:-6%>3)$%:=>#+%2+%
#"#-% 4-"#+>% >3#% 92->+:$>
<Y
'% 12% +#92+6% *:4>3*)=% 34D3A+#$2=)>42-% 4]:D#$% 4>% 9:-% >3#+#*2+#% H#%
3#=G*)=% >2% 4]:D#% )-i-2`-% H42=2D49:=% $R$>#]$% 4-% >3#% G+#$#-9#% 2*% $>+)9>)+:==R% `#==A
93:+:9>#+4@#6%+#*#+#-9#%$:]G=#$
<Y0B<0BB
'%%
5GG=4#6% >2% 9#==)=:+% $R$>#]$% 92->:9>% :-6%
6R-:]49%]26#%5&?%+#"#:=% >2G2D+:G3$%H#=2`%>3#%
+#$2=)>42-%=4]4>%2*%92-"#->42-:=%=4D3>%]49+2$92GR'%13#%#:$#%2*%)$#%:-6%>3#%#P9#G>42-:=%$4D-:=A