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Pioneering Nanofluidics

Posted: Feb. 21, 2019

Award Recipient: Prof. Takehiko Kitamori School of Engineering, The University of Tokyo

Professor Kitamori developed a thermal lens microscope TLM which can detect and determine non-fluorescent molecules in liquid hyper-sensitively. His microchemical chip which was spinoff of a micro sample vessel and flow switching device for ultra-small liquid samples of the TLM is one of the sources of microfluidics today (CSJ Award for Creative Work, 2006). Since then, he has devoted himself to pioneer nanofluidics and to realize nanofluidic devices. As the result, he developed a variety of novel technologies, outstandingly innovated analytical chemistry in which sample volume became fL and aL and limit of determination evolved from mol to number of molecules, found unique properties of liquids in nanospace which was smaller than the wavelength of light, and brought impacts to the other science fields by these achievements. Thus, Professor Kitamori pioneered innovative scientific area, that is nanofluidics, which is essentially different from microfluidics. His main achievements are introduced below.

1. Establishing methodologies and underlying technologies for nanofluidics
Professor Kitamori developed the concept to realize nanofluidic devices, which consists of three main strategies, 1) size hierarchy structure, 2) nano unit operation NUO, 3) laser spectroscopic readout. He fabricated nanochannels at 10nm and 100nm orders on glass substrates which can stably maintain nano structures by using electron beam drawing and plasma anisotropic etching. He also realized nano-patterning surface modification methods in/on nanochannels with the functional molecules such as hydrophilic group, hydrophobic group, antibody, and catalyst by using electron beam and VUV light ablations and liftoff fabrication methods in addition to the ordinary chemical glass surface modification methods. In addition, he innovated on glass bonding method, and realized the low temperature bonding method in which free water molecules and siloxane coupling between two glass substrates were controlled by oxygen and fluorine plasma surface treatment. The low temperature bonding method brought a big breakthrough to realize a variety of nanofluidic devices, because it didn't damage on the surface modification even if the cover glass was bonded after partial-nanopatterning of nanochannel surfaces by functional molecules. Detection on the nanofluidic device is based on the TLM which is his powerful original detection tool for non-fluorescent molecules, however, geometric optics doesn't work in the nanochannel which is smaller than the wavelength of the prob laser beam in principle. Then, Professor Kitamori developed the differential interference contrast TLM (DIC-TLM) in which wave optics was introduced. The DIC-TLM detects small change of refractive index of the liquid sample in a nanochannel by phase shift of the prob laser beam caused by heat energy from photo absorption and non-radiative relaxation of the target molecules, and it is extremely highly sensitive for the target molecules in nanochannels. It has become powerful detection tool for study of nanofluidic devices.

2. Coming true, nanofluidics and nanofluidic devices
Professor Kitamori realized nanofluidics and nanofluidic devices by making above technologies full use skillfully. First, he put a variety of nano unit operations NUOs such as mixing and reaction into practice. For example, he proved the concept of nano solvent extraction in a 800nm channel half of which 400nm was hydrophobized and the other half 400nm was kept hydrophilic. Other kinds of NUOs in various phases like solid phase separation by antigen-antibody reaction, evaporation, and condensation were also developed. Furthermore, he combined those NUOs in serial and parallel and proved that continuous flow chemical processing could be configured even in nano scale. In total, he established the foundation of nanofluidics the first time in the world by using channels which were narrower than the wavelength of light.
Regarding the functional nanofluidic devices, Professor Kitamori is the world's first scholar who realized and proved the excellent functions of the fL immunoassay device, aL chromatography, solar driven fuel cell device, nano heat pump, and so on. For example, his single cell ELISA device integrated all the processes of single cell handling and fL molecular analysis onto one glass substrate, and he demonstrated single cell stimulation, cytokine release, fL sampling, and determination of cytokine molecules at countable number molecule levels. Actually, his group has succeeded in determination of IL-6 molecules at countable levels from single B cell, and he developed it as a tool of the single cell pathology to elucidate autoimmunological diseases by collaborating with the researchers of the university hospital. A combination with fl-LC to this device is also expected to be a novel tool for single cell proteomics and metabolomics.

3. Solution chemistry in liquid nanospace
During the history of his research, Professor Kitamori found that liquids in nanochannels possess completely different properties as chemical solutions and different characteristics as physical fluids from macroscale liquids. For examples, viscosity of water increased about 4 times and dielectric constant became 1/7, and proton mobility was 20 folds and conductivity was 500 folds higher than the water in usual macro space. Furthermore, water molecules just on the nanochannel surface flew with slipping, although velocity has to become zero at the surface according to usual fluid mechanics. Some functional devices described above utilized these unusual properties and characteristics of nanofluidics.
Liquid phase nanospace is unusual space in which the effects of the surface functional groups reach to entire space. Especially, in the water of nanochannels, proton diffusion was found to be the Grötthuss type hopping diffusion and the diffusion was highly affected by the proton donner properties of the surface functional groups of the channels, and therefore, Professor Kitamori proposed the proton transfer phase model in which the proton mobility is enhanced within 101 nm area from the surface and put forward the possibility of the novel solution chemistry and fluid chemistry in the liquid/solid interfacial nano space. However, his model isn't inconsistent with the ordinary electrochemistry nor interfacial chemistry which is dominated by the surface charge, and it proposes the molecular picture of loosely coupled molecule configuration by the proton hopping.
The nanofluidics by Professor Kitamori pioneers completely new research field, that is the designed and fabricated liquid nanospace. The liquid nanospace is similar sized space to the synaptic cleft, and the nanofluidic device may also provide an important research tool to the life sciences.

As described above, Professor Kitamori was the first in the world to realize the nanofluidics and nanofluidic devices, and he attracted many followers and founded a completely new research area. The area of analytical chemistry was extended to fL and aL volume, the ordinary chemistry with the unit of mole was innovated to chemistry at number of molecules, and then, the novel research field of liquid nanospace was opened. Thus, he gave impacts not only on analytical chemistry and microfluidics which was already established worldwide but also on single cell science and single cell pathology, and the nanofluidic devices is expected to provide novel experimental tools which will bring innovative breakthrough in these research fields. Professor Kitamori is an internationally admired and renowned scholar, and he contributed much to the domestic and international communities of these fields as the founder, the first President, or the Vice President. And thus, Professor Kitamori's great contributions deserves well to the Chemical Society of Japan(CSJ) Award.