SMART - Singapore MIT Alliance for Research and Technology

Singapore-MIT Alliance for Research & Technology

Biosystems and Micromechanics

BioSystems and Micromechanics (BioSyM) Inter-Disciplinary Research Group

SMART BioSyM @ MicroTAS-2011

BioSyM researchers and graduate students along with their collaborators presented 6 papers in MicroTAS-2011 Conference @ Seattle, Washington, USA

  • RAPID MICROWELL PROTOTYPING, GENERATION OF 3D MULTICELLULAR CANCER AGGREGATES, AND EMT DRUG SCREENING

T.-Y.Tu(1,3), W. Sun(1), W.K. Peng(1), Z. Wang(1), R.Y.J. Huang(4), P.T. Matsudaira(3), J.-P. Thiery(2), and R.D. Kamm(1)
(1) BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology (SMART) Center, Singapore
(2) A*STAR Institute of Molecular Cell Biology (IMCB), Singapore
(3) Mechanobiology Institute (MBI), National University of Singapore, Singapore
(4) Cancer Science Institute (CSI), National University of Singapore, Singapore

ABSTRACT
This work presents a microwell prototyping technique for generating multicellular cancer aggregates in suspension culture for epithelial-mesenchymal-transition (EMT) drug screening. Microwell and aggregate size and geometry were examined in PMMA, PDMS, polystyrene materials materials. Retrieved aggregates were further studied in terms of cell dispersion through drug screening, to identify the effective drug dosage for the inhibition of EMT. Two distinct cell phenotypic behaviors were discovered from Low-attachment-dish- and microwell-generated aggregates under different conditions. Future studies of the two types of aggregates may contribute to the understanding of cancer metastasis.

  • DEAN FLOW FRACTIONATION (DFF) ISOLATION OF CIRCULATING TUMOR CELLS (CTCs) FROM BLOOD

Ali Asgar S. Bhagat(1) , Han Wei Hou(1,2), Leon D. Li(3), Chwee Teck Lim(1,2,4), Jongyoon Han(1,5,6)
(1) BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology (SMART) Centre, SINGAPORE
(2) Division of Bioengineering, National University of Singapore, SINGAPORE
(3) Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA
(4) Mechanobiology Institute, SINGAPORE
(5) Department of Electrical Engineering & Computer Science, MIT, Cambridge, MA, USA
(6) Department of Biological Engineering, MIT, Cambridge, MA, USA

ABSTRACT
Isolation and enumeration of circulating tumor cells (CTCs) as cancer biomarkers have been challenging due to their ex-tremely low abundance in blood. This paper reports an ultra high-throughput technique for CTCs isolation from blood using the inherent Dean vortex flows present in curvilinear channels, aptly termed Dean Flow Fractionation (DFF). Using a 2-inlet 2-outlet spiral microchannel, the separation principle exploits the difference in cell size between CTCs (~16-20 μm diameter) and other blood cells (RBCs ~8 μm; leukocytes ~8-14 μm). Experimental results confirm >99% RBCs and leukocytes re-moval from blood sample (20% hematocrit) spiked with MCF-7 cells with >90% tumor cell recovery after separation. The developed technique offers large sample processing capability due to its ability to process very high hematocrit samples (20%), a key requirement for isolating rare-cells. A single device can process 1 mL whole blood in a single step, under 15 min.

  • MICROFLUIDIC MANIFOLD SYSTEM TO REDUCE THE NUMBER OF SYRINGE PUMPS IN MULTI-PHASE SYSTEMS FOR GENERATING
    ALGINATE BEADS

Choong Kim(1,2), Jae Hoon Bang(1), Young Eun Kim(1), and Ji Yoon Kang(1)
(1) Korea Institute of Science and Technology, KOREA
(2) BioSystems nad Micromechanics, Singapore-MIT Alliance for Research and Technology (SMART) Centre, SINGAPORE

ABSTRACT
This paper proposes a microfluidic manifold system for the generation of uni-form-sized alginate beads to reduce the
number of syringe pumps. Flow rates of fluids (calcified oleic acid, alginate solution including cells, and mineral oil) are
con-trolled by a microfluidic manifold to control the flow rates, and more mono-disperse beads were generated by one syringe pumps than by 4 syringe pumps.

  • A NEW IN VIVO-MIMIC ANGIOGENESIS MI-CROFLUIDC PLATFROM FOR THE STUDY OF CELL ENCAPSULATION BASED CELL THERAPY

Choong Kim(1), Min-Cheol Kim(1), Seok Chung(4), H. Harry Asada(1,2), and Roger D. Kamm(1,2,3)
(1) BioSystems nad Micromechanics, Singapore-MIT Alliance for Research and Technology (SMART) Centre, SINGAPORE
(2) Department of Biological Engineering, MIT, USA
(3) Department of Biological Engineering, MIT, USA
(4) Korea University, KOREA

ABSTRACT
In this paper, we have developed a novel in vitro angiogenesis on a chip to identify potential molecular targets, secreted
from cell encapsulated beads; augmenting, altering and blocking endothelial cell responses, and to enable preliminary screening before transplantation. We confirmed that growth factors secreted from the encapsulated cells in CE beads were able to induce ECs migration and form lumen-like structures in the collagen scaffold.

  • SIZE-INDEPENDENT DEFORMABILITY CYTOMETRY WITH ACTIVE FEEDBACK CONTROL OF MICROFLUIDIC CHANNELS

Guofeng Guan(1,2), Ali Asgar Bhagat(2), Weng Kung Peng(2), Wong Cheng Lee(2,3), Chong Jin Ong(1), Peter C. Y. Chen(1,2), and Jongyoon Han(2,4,5)
(1) Department of Mechanical Engineering, National University of Singapore, Singapore
(2) Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology (SMART), Singapore
(3) Department of Bioengineering, National University of Singapore, Singapore
(4) Department of Biological Engineering, Massachusetts Institute of Technology, USA
(5) Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, USA

ABSTRACT
Mechanical properties of cells can be correlated with various cell states and are now considered as an important
biophysical marker. While there are many microfluidic and other techniques emerged recently to assay cell mechanical
properties, most of them are affected by the inherent cell size variation of a given cell population. In this work, we present a new microfluidic technique with real-time feedback control system to evaluate single cell deformability while minimizing cell-size dependence of the measurement. We demonstrate the device using breast cancer cells (MCF-7) as well as primary human mesenchymal stem cells (hMSCs). It is anticipated that this system would be useful to profile the stiffness of cells in a complex, diverse cell populations such as mesenchymal stem cells.

  • PATHOGEN AND INFLAMMATORY COMPONENTS REMOVAL FROM BLOOD USING CELL MARGINATION

H.W. Hou(1,2) , H.Y. Gan(3), A.A.S. Bhagat(1), L.D. Li(4), C.T. Lim(1,2,5), J. Han(1,3,6)
(1) BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology (SMART) Centre, SINGAPORE
(2) Division of Bioengineering, National University of Singapore, SINGAPORE
(3) Department of Electrical Engineering & Computer Science, MIT, Cambridge, MA, USA
(4) Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA
(5) Mechanobiology Institute, National University of Singapore, SINGAPORE
(6) Department of Biological Engineering, MIT, Cambridge, MA, USA

ABSTRACT
Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a novel
microfluidic approach for non-specific removal of both pathogen and inflammatory cellular components from whole blood
directly using cell margination. A high microbial removal efficiency of >80% was achieved in our device consisting of 2
cascaded microchannels in series, thus allowing a 2-stage removal of microbes in a single step. ~90% of platelets and leukocytes were also successfully removed from the blood which can be used to modulate the host inflammatory responses and potentially as a blood cleansing method for sepsis treatment.