This page is for a novel commercial product produced by a company RIBM basedon the Biophysical instrument developed by researchers

High-speed Atomic Force Microscope
Toshio Ando, Noriyuki Kodera & Takayuki Uchihashi (Dept. of Physics, Kanazawa Univ.)
We long have had to infer how proteins function fromhigh-speed imaging compatible with low-invasive

the static snapshots of their structure and the dynamicimaging. Through these long efforts, the HS-AFM ofbehavior of optical makers attached to the molecules.

practical use was built at last in 2008 [2].

Therefore, directly observing protein molecules inThe feedback bandwidth has now reached ~100 kHz,

dynamic action at high spatiotemporal resolution hasand therefore, biological molecules can be imaged at ~12long been a holy grail for biological science. To makeframes/s (fps) or faster, without their function being

this long quested dream real, Ando embarked on thedisturbed. It is now rather becoming common to film

development of a high-speed atomic force microscope

dynamic processes of protein molecules by HS-AFM to(HS-AFM) in 1993. AFM is a unique imaging tool thatfind how the proteins act to function (see Review [3]).

enables high resolution visualization of objects made of

For example, bacteriorhodopsin showing photo-induced

any material in any environment. However, it takes at

structural changes [4], myosin V walking on actin

least 30 s (usually minutes) to capture an image.

filaments [5], F1-ATPase exhibiting rotary propagation

In the early stage, we focused on developing a fastof conformational changes [6] have been visualized withscanner, a fast amplitude detector, small cantilevers withunprecedented clearness (Fig. 1). These video images

high resonant frequencies and small spring constants,

newly uncovered molecular actions, bringing greaterand an optical beam deflection detector for the small

insights into their functional mechanism.

cantilevers. The first prototypic HS-AFM setup built inReference

2001 [1] was tested for myosin V but found to be

1. T. Ando et al. PNAS USA 98, 12468-12472 (2001).

insufficient in both speed and low- invasive

2. T. Ando et al. Prog. Surf. Sci. 83, 337-437 (2008).

performances. Then, we developed active damping3. T. Ando et al. Chem. Rev. 114, 3120-3188 (2014).

techniques to suppress the scanner’s unwanted vibrations
as well as to increase its response speed. Moreover, wedevised a new feedback control scheme to make4. M. Shibata et al. Nat. Nanotechnol. 5, 208 – 212(2010).
5. N. Kodera et al. Nature 468, 72-76 (2010).
6. T. Uchihashi et al. Science 333, 755-758 (2011).
Fig. 1. Protein molecules indynamic action captured by HSAFM. (A) myosin V walking onan actin filament, (B) F1-ATPasewith rotating conformationalchanges, (C) bacteriorhodopsin
responding to light. Imaging
rate: 7 fps (A), 12.5 fps (B), 1fps (C).

This page is for a novel commercial product produced by a company RIBM basedon the Biophysical instrument developed by researchers

NanoExplore TM (NEX)
Takao Okada, Norito Kotani & Takashi Morii (Research Institute of Biomolecule MetrologyCo., Ltd.)
Noticing the potential of high-speed AFM and aiming
at its commercialization, RIBM has been collaboratingwith Ando’s lab of Kanazawa University since ten
years ago. In cooperation with five oversea
Universities, Ando’s lab founded the international
consortium on High-speed bio-AFM. RIBM joined
this consortium by producing and supplying theprototypic high-speed AFM to the oversea members.
Through these activities, RIBM learned techniques
constituting the instrument, accumulated know-hows

Fig. 2. High-speed AFM NanoExploreTM

of producing them and also explored applications ofmultiple units of NEX after recognizing its value. InHS-AFM. RIBM turned Ando’s high-speed AFM intoaddition, not only from United States and Europe,

a commercial product, as NanoExplorer (NEX). Since

there are continuing inquiries also from countries in2011, we have been manufacturing and selling theMiddle East and Asia. Thus, further expansion of sales

product to domestic and oversea research institutes

to overseas is expected.

and providing the customers with support services.

The customer laboratories are using NEX to study

In the world market, NEX is one of two

dynamics of, for example, a variety of membranecommercial products that allow video capturing

proteins, membrane scission proteins, interaction ofbiomolecules in physiological solution. Its highest

antigen-antibody, self-assembly of amyloid fibrils andimaging rate is 0.05 sec per frame. As a side effect ofmembrane pore-forming proteins, interaction between

this high-speed performance, NEX is less susceptible

DNA and DNA-related enzymes, opening and closing

to floor vibrations and mechanical drift. Moreover, theof ion channels and transport in nuclear pore. Also,

effect of system parameter changes appears

some customers are using NEX to observe dynamics

immediately on the acquired image, easing the systemoccurring in live cells including neurons. Other thanoperation. Also in this regards, NEX is superior toNEX, there are no products allowing these studies andconventional AFM.

therefore, further expansion of NEX users is certain.

The market of conventional AFM has been

In 2015, RIMB started selling PS-NEX that scansmaturing, resulting in intense price competition andthe cantilever chip, rather than scanning the sample

shrinking market. Under such circumstances, NEX

stage. PS-NEX can use large and heavy samples andthat has brought a qualitative change from still tobe combined with fluorescent microscopes. From thisvideo imaging is now creating a new growing market.

capability it is expected that PS-NEX will contribute

In fact, NEX has already been sold to a number of

not only to basic research of biomolecules but also todomestic and oversea institutions. The overseas

life science in general as well as material sciences.

countries include Australia, Canada, France,

Biophysics has been advancing through creating

Netherlands, Switzerland, United States and others.

and using new measurement techniques. RIBM hopes

There are overseas laboratories that have purchased

to be of more help in progress of Biophysics.