Nobuyuki Futai

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems

We describe a microfabricated airway system integrated with computerized air–liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.

Selective drive of electrostatic actuators using remote inductive powering

A remote inductive powering system for driving electrostatic actuators is proposed. The actuators can be controlled selectively by matching transmitters frequency to the resonance frequency of the receiver LC-circuits. A 8.5 mm/spl times/7.2 mm square and 20 turns planar coil are used as a receiver coil. The maximum output voltage of the receiver was measured about 45 V when a load resistance is more than 100 k/spl Omega/. A conventional electrostatic comb actuator was used for a prototype of the remote powering system. The coil and the actuator were fabricated on the same surface of a commercially available silicon on insulator (SOI) wafer. The displacement of the actuators were selectively controlled by changing the transmitters frequency.

Microfluidic model of bubble lodging in microvessel bifurcations

The lodging mechanisms and dynamics of cardiovascular gas bubbles are investigated in microfluidic model bifurcations made of poly(dimethylsiloxane). This work is motivated by gas embolotherapy for the potential treatment of cancer by tumor infarction. The results show that the critical driving pressure below which a bubble will lodge in a bifurcation is significantly less than the driving pressure required to dislodge it. From the results the authors estimate that gas bubbles from embolotherapy can lodge in vessels 20μm or smaller in diameter, and conclude that bubbles may potentially be used to reduce blood flow to tumor microcirculation.

Fabrication of high-aspect-ratio PZT thick film structure using sol-gel technique and SU-8 photoresist

An optimized sol-gel process and an SU-8 photoresist were used to produce thick and high-aspect-ratio lead zirconate titanate (PZT) structures on platinized silicon substrates. The fabrication process involved single coating, lapping of the gel, and rapid firing. The PZT structures made with this new process were crack-free and had good crystallinity. Their XRD patterns and ferroelectric properties showed that the structures were high quality PZT. Values of relative permittivity and dielectric loss of the PZT were over 300 and 0.03, respectively. The structures had thickness of 20 /spl mu/m or higher, and had aspect ratio of over one.

On-chip multi-gas incubation for microfluidic cell cultures under hypoxia

We developed a simple system that regulates CO2 and O2 levels within a microfluidic chip. This system enables long-term cell culture under hypoxic conditions without the need of a CO2 incubator or a multi-gas incubator. Hypoxic conditions were generated using a miniature water jacket containing dissolved ascorbate as an oxygen scavenger. Formulations of the water jacket were determined that enables both 5% pCO2 and desired pO2 levels ranging from 5 to 15%. We also cultured PC-12 cells and primary neuronal cells from chick embryos under hypoxia and observed hypoxia-induced cell death and inhibition of neurite outgrowth.

A microfluidic static gradient generator using limited diffusuon through T-shaped narrow channels

We have developed a poly (dimethylsiloxane) (PDMS)-cast microfluidic chip that contains a thin (cross-sectional area less than 1.0 μm2) but high aspect ratio (1:1 ~ 1:3) microchannels. Experimental results showed that the gradient of an example of test substances (sodium fluorescein) remained constant in the thin channel over a long period of time (30 minutes) by simple manual liquid handling. We aim to develop a thinner channel keeping the gradient longer time.

At the Interface: Advanced Microfluidic Assays for Study of Cell Function

Understanding basic biology and disease mechanisms, testing drug safety and efficacy, engineering tissues and cell-based biosensors all require methods to study and manipulate mammalian cell function. A convenient method that has been developed over the past century for these purposes is in vitro cell culture where cells are taken out of their normal physiological environment inside the body and kept alive in a dish. Although in vitro cell culture is powerful, there is increasing evidence that cellular responses in culture dishes do not necessarily reflect how cells may behave in vivo. This discrepancy is due, at least in part, to the fact that much of what happens in living organisms is affected by microscale patterns and heterogeneity which are not well controlled in traditional macroscopic culture systems. Cells, which are micron-sized, determine their behavior based on cues from their microenvironment. Cellular behaviors such as subcellular signaling, chemotaxis (directed migration towards a chemical), growth, differentiation, and death, for example, are determined by subcellular stimulation, microscale chemical gradients, and adhesive micro- & nanopatterns. Microfluidics and other microscale phenomena dominate at this level making microtechnology crucial to the understanding of the cellular basis of life.

Microfluidic Immunoassay for Alveolar Cell Released Interleukin-8 Using a Braille Display for Computer-Controlled Fluid Actuation

We have developed a self-contained, connectorless, automated microfluidic immunoassay system to detect and quantify levels of Interleukin (IL)-8, an important cytokine involved in the inflammatory response. In our microfluidic system, liquid flow is controlled using the pins of a commercially available, refreshable Braille display that act as small mechanical actuators. The successful development of such a microsystem will prove beneficial in both the early diagnosis and treatment of various disease states. Integration of the microfluidic immunoassay system with cell culture can provide a novel, self-contained device to analyze the by-products of chemically stimulated cells in a controlled microenvironment

Simulation, fabrication and evaluation of microinductor-based artificial tactile mechanoreceptor embedded in PDMS

A micromachined planar spiral inductor was created for the use of a passive mechanoreceptor element in a practical skin-like tactile sensor. This paper shows the results of a simulation of the receptor element that changes inductance when largely deformed. We also report a modified method of fabrication that improves durability dramatically. Finally, we evaluated the validation of the simulation method.

Remodeling in synthetic vascular network - experiment and modeling

Vascular network is first generated by vasculogenesis and angiogenesis. The vessel diameters are later modified by vascular flow, which is called remodeling process. Various theoretical models were proposed for this remodeling process to explain vascular patterns in vivo. However, if we fully understand the mechanism of pattern formation, we should be able to generate the vascular pattern from scratch. In the present study, we utilized a microdevice to generate perfusable vascular network (Kim et al., 2013), and established a long-term perfusion method using braille display. Synthetic vasculature first starts as an irregular network. Then the endothelial cells in the microdevice exhibits remodelling process. Unused part of the vascular bed gradually disappears, resulting in one thick blood vessel in the devise. First, we formulated a model to explain the early phase of network formation. Time-lapse observation of first 12 hours of culture revealed the endothelial cell dynamics. The cultured cells seldom moved but extended long protrusions, and stochastic collisions of the protrusion and cell body established the connections between cells. Effect of neighbouring cell on formation and elongation of protrusion is not observed. Based on these findings, we use stochastic model with experimentally measured parameter to reproduce the initial phase of meshwork formation in this culture system. Next, we established amodel to reproduce the remodelling process in a microdevice. We utilized a simple model in which vessel wall change its position for optimized share stress value. We implemented the vessel wall change by phase field method, and the Stokes flow by MAC method. The numerical simulation reproduces pruning process observed in the microdevice, and final thickness of remaining vasculature can be obtained analytically.