Turing Instability in Reaction-Diffusion Systems with a Single Diffuser: Characterization Based on Root Locus

Cooperative behaviors arising from bacterial cell-to-cell communication can be modeled by reaction-diffusion equations having only a single diffusible component. This paper presents the following three contributions for the systematic analysis of Turing instability in such reaction-diffusion systems. (i) We first introduce a unified framework to formulate the reaction-diffusion system as an interconnected multi-agent dynamical system. (ii) Then, we mathematically classify biologically plausible and implausible Turing instabilities and characterize them by the root locus of each agent's dynamics, or the local reaction dynamics. (iii) Using this characterization, we derive analytic conditions for biologically plausible Turing instability, which provide useful guidance for the design and the analysis of biological networks. These results are demonstrated on an extended Gray-Scott model with a single diffuser

Coordinated Spatial Pattern Formation in Biomolecular Communication Networks

This paper proposes a control theoretic framework to model and analyze the self-organized pattern formation of molecular concentrations in biomolecular communication networks, emerging applications in synthetic biology. In biomolecular communication networks, bio-nanomachines, or biological cells, communicate with each other using a cell-to-cell communication mechanism mediated by a diffusible signaling molecule, thereby the dynamics of molecular concentrations are approximately modeled as a reaction-diffusion system with a single diffuser. We first introduce a feedback model representation of the reaction-diffusion system and provide a systematic local stability/instability analysis tool using the root locus of the feedback system. The instability analysis then allows us to analytically derive the conditions for the self-organized spatial pattern formation, or Turing pattern formation, of the bionanomachines. We propose a novel synthetic biocircuit motif called activator-repressor-diffuser system and show that it is one of the minimum biomolecular circuits that admit self-organized patterns over cell population

電場パターンの時空間制御に基づくソフトマターの誘導自己組織化

学位の種別: 課程博士審査委員会委員 : （主査）東京大学講師 星野 隆行, 東京大学教授 生田 幸士, 東京大学教授 奈良 高明, 東京大学准教授 眞渓 歩, 東京大学講師 池内 真志University of Tokyo(東京大学

L-2L ladder digital-to-analogue converter for dynamics generation of chemical concentrations

Cellular response to dynamic chemical stimulation encodes rich information about the underlying reaction pathways and their kinetics. Microfluidic chemical stimulators play a key role in generating dynamic concentration waveforms by mixing several aqueous solutions. In this article, we propose a multi-layer microfluidic chemical stimulator capable of modulating chemical concentrations by a simple binary logic based on the electronic-hydraulic analogy of electronic R-2R ladder circuits. The proposed device, which we call L-2L ladder digital-to-analogue converter (DAC), allows us to systematically modulate 2n levels of concentrations from single sources of solution and solvent by a single operation of 2n membrane valves, which contrasts with existing devices that require complex channel geometry with multiple input sources and valve operations. We fabricated the L-2L ladder DAC with n = 3 bit resolution and verified the concept by comparing the generated waveforms with computational simulations. The response time of the proposed DAC was within the order of seconds because of its simple operation logic of membrane valves. Furthermore, detailed analysis of the waveforms revealed that the transient concentration can be systematically predicted by a simple addition of the transient waveforms of 2n = 6 base patterns, enabling facile optimization of the channel geometry to fine-tune the output waveforms

Spatiotemporal Control of Electrokinetic Transport in Nanofluidics Using an Inverted Electron-Beam Lithography System

Manipulation techniques of biomolecules have been proposed for biochemical analysis which combine electrokinetic dynamics, such as electrophoresis or electroosmotic flow, with optical manipulation to provide high throughput and high spatial degrees of freedom. However, there are still challenging problems in nanoscale manipulation due to the diffraction limit of optics. We propose here a new manipulation technique for spatiotemporal control of chemical transport in nanofluids using an inverted electron-beam (EB) lithography system for liquid samples. By irradiating a 2.5 keV EB to a liquid sample through a 100-nm-thick SiN membrane, negative charges can be generated within the SiN membrane, and these negative charges can induce a highly focused electric field in the liquid sample. We showed that the EB-induced negative charges could induce fluid flow, which was strong enough to manipulate 240 nm nanoparticles in water, and we verified that the main dynamics of this EB-induced fluid flow was electroosmosis caused by changing the zeta potential of the SiN membrane surface. Moreover, we demonstrated manipulation of a single nanoparticle and concentration patterning of nanoparticles by scanning EB. Considering the shortness of the EB wavelength and Debye length in buffer solutions, we expect that our manipulation technique will be applied to nanomanipulation of biomolecules in biochemical analysis and control

Spatiotemporal Control of Electrokinetic Transport in Nanofluidics Using an Inverted Electron-Beam Lithography System

Manipulation techniques of biomolecules have been proposed for biochemical analysis which combine electrokinetic dynamics, such as electrophoresis or electroosmotic flow, with optical manipulation to provide high throughput and high spatial degrees of freedom. However, there are still challenging problems in nanoscale manipulation due to the diffraction limit of optics. We propose here a new manipulation technique for spatiotemporal control of chemical transport in nanofluids using an inverted electron-beam (EB) lithography system for liquid samples. By irradiating a 2.5 keV EB to a liquid sample through a 100-nm-thick SiN membrane, negative charges can be generated within the SiN membrane, and these negative charges can induce a highly focused electric field in the liquid sample. We showed that the EB-induced negative charges could induce fluid flow, which was strong enough to manipulate 240 nm nanoparticles in water, and we verified that the main dynamics of this EB-induced fluid flow was electroosmosis caused by changing the zeta potential of the SiN membrane surface. Moreover, we demonstrated manipulation of a single nanoparticle and concentration patterning of nanoparticles by scanning EB. Considering the shortness of the EB wavelength and Debye length in buffer solutions, we expect that our manipulation technique will be applied to nanomanipulation of biomolecules in biochemical analysis and control