Control of Oscillation Patterns in a Symmetric Coupled Biological Oscillator System

A chain of three-oscillator system was constructed with living biological oscillators of phasmodial slime mold, Physarum polycehalum and the oscillation patterns were analyzed by the symmetric Hopf bifurcation theory using group theory. Multi-stability of oscillation patterns was observed, even when the coupling strength was fixed. This suggests that the coupling strength is not an effective parameter to obtain a desired oscillation pattern among the multiple patterns. Here we propose a method to control oscillation patterns using resonance to external stimulus and demonstrate pattern switching induced by frequency resonance given to only one of oscillators in the system

Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system

The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis. This induces a high risk of sample loss of the collected rare cells. Here, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood concentration of the peripheral blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at a recovery of 76.2 ± 5.9% of the cancer cells and a minute contamination of 0.12 ± 0.04% PBMCs while simultaneously enabling a 20x volumetric concentration. This constitutes a first step towards a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice

Retrograde axonal transport of Poliovirus and EV71 in motor neurons

Poliovirus (PV) can spread through neural pathway to the central nervous system and replicates in motor neurons, which leads to poliomyelitis. Enterovirus 71 (EV71), which is closely related to PV, is one of the causative agents of hand-foot-and-mouth disease and can cause severe neurological diseases similar to poliomyelitis. Since PV is similar to EV71 in its motor neurotoxicity, we tried to understand if the results obtained with PV are of general applicability to EV71 and other viruses with similar characteristics. Using microfluidic devices, we demonstrated that both PV capsid and the PV genome undergo axonal retrograde transport with human PV receptor (hPVR), and the transported virus replicated in the soma of hPVR-expressing motor neurons. Similar to PV in hPVR-transgenic (Tg) mice, neural pathway ensuring spreading of EV71 has been shown in adult human scavenger receptor class B, member 2 (hSCARB2)-Tg mice. We have validated this finding in microfluidic devices by showing that EV71 is retrogradely transported together with hSCARB2 to the cell body where it replicates in an hSCARB2-dependent manner

研究速報 : Lab-on-a-chip : Towards the Miniaturization and Integration of Fluorescence Spectroscopy Based Detection Method onto Portable Device

特集2 日仏マイクロメカトロニクス国際共同研究組織(LIMMS

Periodicities of palaeo-climatic records extracted from the Dome Fuji deep core

The Antarctic ice sheet preserves palaeo-climate information in the form of physical and chemical stratigraphy. A deep ice core was continuously drilled down to a depth of 2503m at Dome Fuji Station, East Dronning Maud Land, Antarctica, during the 1993-97 JARE inland operations. A time scale for the Dome Fuji core is calculated from past accumulation rates and an ice flow model. A depth-age profile was obtained for the past 320kyr back in time. The obtained palaeo-temperature profile shows the past three glacial and interglacial periods. The power spectrum for oxygen isotope variation for 320kyr shows three dominant cycles of 107kyr, 40kyr and 21kyr. Each of these three cycles is similar to Milankovitch cycles. Moving-window spectrum analysis, using a 130kyr window stepped by 10kyr over the past 320kyr, found these main cycles in every age. Variations of other chemical concentrations were also recovered from the Dome Fuji ice core, and are inversely correlated to the temperature profile. Concentrations of terrestrial and marine origin substances are high in glacial periods, and low in interglacial periods. Over the past 320kyr, the dominant periodicities of temperature were also detected in almost all chemical records

Modulation of Hepatocarcinoma Cell Morphology and Activity by Parylene-C Coating on PDMS

BACKGROUND: The ability to understand and locally control the morphogenesis of mammalian cells is a fundamental objective of cell and developmental biology as well as tissue engineering research. We present parylene-C (ParC) deposited on polydimethylsiloxane (PDMS) as a new substratum for in vitro advanced cell culture in the case of Human Hepatocarcinoma (HepG2) cells. PRINCIPAL FINDINGS: Our findings establish that the intrinsic properties of ParC-coated PDMS (ParC/PDMS) influence and modulate initial extracellular matrix (ECM; here, type-I collagen) surface architecture, as compared to non-coated PDMS substratum. Morphological changes induced by the presence of ParC on PDMS were shown to directly affect liver cell metabolic activity and the expression of transmembrane receptors implicated in cell adhesion and cell-cell interaction. These changes were characterized by atomic force microscopy (AFM), which elucidated differences in HepG2 cell adhesion, spreading, and reorganization into two- or three-dimensional structures by neosynthesis of ECM components. Local modulation of cell aggregation was successfully performed using ParC/PDMS micropatterns constructed by simple microfabrication. CONCLUSION/SIGNIFICANCE: We demonstrated for the first time the modulation of HepG2 cells' behavior in relation to the intrinsic physical properties of PDMS and ParC, enabling the local modulation of cell spreading in a 2D or 3D manner by simple microfabrication techniques. This work will provide promising insights into the development of cell-based platforms that have many applications in the field of in vitro liver tissue engineering, pharmacology and therapeutics

Sensing of Oxygen Concentration in a Microfluidic Device mimicking Liver 3D Microarchitecture

International audienceWe designed a microfluidic structure which closely reproduces liver microarchitecture, constraining primary rat hepatocytes at a high density and in three dimensions (3D), and in which a gradient of oxygen can be generated. The device includes an oxygen sensitive membrane that could map the oxygen consumption of hepatocytes. INTRODUCTION Compared to classical two-dimensional cell culture, microfluidic devices or/and 3D culture conditions were evidenced to increase the period of time during which primary hepatocytes retain their functions [1]. Moreover, microfluidic techniques offer the opportunity to mimic the in vivo hepatocyte zonation, by subjecting hepatocytes to oxygen gradients [1-2]. Such oxygen gradients that can be estimated by numerical simulations, were recently experimentally assessed using an oxygen sensitive fluorescent membrane [3]. We proposed to include the oxygen sensitive membrane within a miniaturized fluidic device mimicking several hepatic cords in series, and inducing a gradient of oxygen on those. Moreover each of those hepatic cord units was inducing 3D organization of hepatocytes, due to the 72 µm height of culture chambers in which they can aggregate