Microfluidic tools for mechanical screening of circulating cells

Microfluidic tools for mechanical screening of circulating cells

Citation for published version (APA):

Hernandez, L. I., Bouten, C. V. C., Anderson, P. D., & Toonder, den, J. M. J. (2009). Microfluidic tools for

mechanical screening of circulating cells. Poster session presented at Mate Poster Award 2009 : 14th Annual

Poster Contest.

Document status and date:

Published: 01/01/2009

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Introduction

Atherosclerosis represents a major risk factor for many

cardiovascular diseases (CVD). At this date it is not

possible to diagnose patients that hide “unstable vulnerable

plaques’’ due to lack of biomarkers with strong positive

predictive values that are able to identify patients with high

risk of developing the disease.

One explored avenue for biomarker searching has

been the circulating cells (e.g. white blood cells) in the

blood. Importantly, when in contact with an injured

endothelium or atherosclerotic plaque, circulating cells

become activated and alter their mechanical properties

and expression patterns[1,2].

Objective

To develop microfluidic-based devices that allow high

throughput mechanical screening and investigation of

circulating cells and their potential as carriers of

biomarkers suitable for discriminating patients with early

stage atherosclerosis or with increased risk of developing

multiple unstable plaques.

Designs and Fabrication

150m

50m 10m

250m

C)

Microfluidic Tools for Mechanical

Screening of Circulating Cells

L.I. Hernandez, C.V.C Bouten, P.D. Anderson, Jaap den Toonder

/ Soft Tissue Biomechanics and Engineering

Figure 2. A. Schematic view of a 3-D microfluidic device assembly. 2 PDMS chips are sandwiched together with a polycarbonate membrane (pore size 0.2m diameter) in between. The bottom layer contains the microfluidic channels and the top layer contains an open reservoir that allows easy introduction of different stimuli.

B. Top view of the microfluidic channel with membrane on top. The design

consists of 2 contraction channels (6m diameters) for mechanical interogation of the cells and a serpentine segment that allows for the incubation and increased reaction time with the applied stimuli on top.

C. Skematic representation of the microfluidic contraction channel for cell

defomation studies.

Design 2

Figure 3. Multi functional microfluidic device for single cell isolation [2], cultivation, mechanical deformation (in the narrow channel that connects the main channel pockets with the buffer channel), chemotaxis and sorting.

Relevant Output

 Cell transit time in the narrow channels

 Cell shape recovery time before and after treatment with

various stimuli

 Pre-screening based on subsequent deformation and

recovery time cycles of single cells from a pool of cells

References

1. D. Versteeg , I.E. Hoefer, A.H. Schoneveld Heart, 94 (2008), 770-776 2. G. Liuzzo, M. Santamaria, L.M. Biasucci J Am Coll Cardiol, 49 (2007),

185-194

3. Y. Yamaguchia, T. Arakawab,d, N. Takedac, Y. Edagawaa, S. Shojib, Sensors and Actuators B: Chemical, 136 (2009) 555–561

.

Response to mechanical and biochemical stress B) outlet stimuli (cytokines) A) PDMS PDMS membrane Design 1