Published papers

© 2017 IEEE. The predictive ability of stochastic chemical reactions is currently limited by the lack of closed form solutions to the governing chemical master equation. To overcome this limitation, this letter proposes a computational method capable of predicting mathematically rigorous upper and lower bounds of transient moments for reactions governed by the law of mass action. We first derive an equation that transient moments must satisfy based on the moment equation. Although this equation is underdetermined, we introduce a set of semidefinite constraints known as moment condition to narrow the feasible set of the variables in the equation. Using these conditions, we formulate a semidefinite program that efficiently and rigorously computes the bounds of transient moment dynamics. The proposed method is demonstrated with illustrative numerical examples and is compared with related works to discuss advantages and limitations.

© 2017 IEEE. The advance of synthetic biology has opened up many potential applications of synthetic biocircuits, including sensing, computation and high-value chemical production using biological cells. To enable rational and robust design of large-scale and complex systems, model-guided design of biocircuits has been increasingly important. Here we review a combined theoretical and experimental platform for model-based optimization of biocircuits. The framework combines feedback control theory and microfluidic technology to enable rapid characterization of biocircuit dynamics in vitro based on advanced mathematical tools in feedback control.

© 2018 The Author(s) Published by the Royal Society. All rights reserved. Model-guided design has become a standard approach to engineering biomolecular circuits in synthetic biology. However, the stochastic nature of biomolecular reactions is often overlooked in the design process. As a result, cell-cell heterogeneity causes unexpected deviation of biocircuit behaviours from model predictions and requires additional iterations of design-build- test cycles. To enhance the design process of stochastic biocircuits, this paper presents a computational framework to systematically specify the level of intrinsic noise usingwell-defined metrics of statistics and design highly heterogeneous biocircuits based on the specifications. Specifically, we use descriptive statistics of population distributions as an intuitive specification language of stochastic biocircuits and develop an optimization-based computational tool that explores parameter configurations satisfying design requirements. Sensitivity analysis methods are also performed to ensure the robustness of a biocircuit design against extrinsic perturbations. These design tools are formulated with convex optimization programs to enable rigorous and efficient quantification of the statistics. We demonstrate these features by designing a stochastic negative feedback biocircuit that satisfies multiple statistical constraints and perform an in-depth study of noise propagation and regulation in negative feedback pathways.

© 2017 IEEE. Model-based prediction of stochastic noise in biomolecular reactions often resorts to approximation with unknown precision. As a result, unexpected stochastic fluctuation causes a headache for the designers of biomolecular circuits. This paper proposes a convex optimization approach to quantifying the steady state moments of molecular copy counts with theoretical rigor. We show that the stochastic moments lie in a convex semi-algebraic set specified by linear matrix inequalities. Thus, the upper and the lower bounds of some moments can be computed by a semidefinite program. Using a protein dimerization process as an example, we demonstrate that the proposed method can precisely predict the mean and the variance of the copy number of the monomer protein.

We recapitulate the notion of phase change rate maximization and demonstrate the usefulness of its solution on analyzing the robust instability of a cyclic network of multi-agent systems subject to a homogenous multiplicative perturbation. Subsequently, we apply the phase change rate maximization result to two practical applications. The first is a magnetic levitation system, while the second is a repressilator with time-delay in synthetic biology.

Polymer microchannels with circular cross-sections for on-off valves are designed and fabricated using the Mosquito method. By demonstrating liquid-flow and by applying load to the fabricated microchannels, we confirm that the microchannels appropriately close to stop flowing the liquid as an on-off valve.

System-level understanding of dynamic biological process requires the measurement of the dynamic response of cells to chemical stimulations with various waveforms. Here, we develop a simple and scalable microfluidic chemical stimulator capable of modulating the concentration waveforms. The proposed device is based on the analogy of an electronic digital-analog converter (DAC), and thereby, the waveforms can be controlled by an intuitive binary logic. We demonstrate dynamic modulation of solution concentrations and perform systematic characterization of the waveforms to enable facile tuning and scale-up of the device.

Recently, molecular communication (MC) has been studied as a micro-scale communication between cells or molecular robots. In previous works, the MC channels in unbounded environment was analyzed. However, many of the experimentally implemented MC channels are surrounded by walls, thus the boundary condition should be explicitly considered to analyze the dynamics of MC channels. In this paper, we propose a framework to analyze the frequency response of one-dimensional MC channels based on a diffusion equation with a boundary. In particular, we decompose the MC channel into the diffusion system and the boundary system, and show the relation between the cut-off frequency of the MC channel and the communication distance based on the transfer function. We then analyze the frequency response of a specific MC channel and reveal that the boundary can restrict the communication bandwidth of the MC channel.