A Biaxial Cell StretcherClient: Frank Yin, MD. Ph.D

Group 30Joshua LeibowitzKrista VedvikChristopher Zarins

Background

• Cells in the body experience mechanical forces• Heart• Lungs• Blood vessels

• Laboratory cell cultures should recreate physiological conditions

Need for a Cell Stretcher

• Studying the effects of mechanical force on aortic endothelial cells• Orientation and organization of cells

depends on stretching• Controlling deformation in both directions

gives the most accurate results

Other Uses of Stretching

•Cardiac—Induce alignment of stem cell derived cardiomyocytes (Tulloch, 2011)•Vascular—Study formation of

aneurysms (Ventikos, 2010)•Respiratory—Study the effects of

protein secretion (Arnold, 2006)

Need for Biaxial Tests

•Most current cell stretching experiments are uniaxial•Limits the validity of results

Scope

Design a device capable of applying 40% strain in two directions• Withstands incubator conditions (37˚C, 100%

humidity)• Maintains calibration over a period of weeks• Easy access to medium to allow for additions and

changes

Current approaches

•Culture on an elastic membrane (Patten, 2005)

•Culture imbedded in a pliable gel (Zile, 2006)

Cell culture

Elastic membraneAdhesion Protein

FlexCell system

•Uses pressure to deform a circular membrane•Applies radial

strain

Calculations

Taking E = 10 kPa, A0 = 1 cm2, L0 = 10 cm, ΔL = 4 cm,

F = 4 N

Required deflection force:

Motor accuracy:Assuming 1.8˚ stepper motor resolution, drive mechanism must have at least 0.2 mm deflection per degree

Design Schedule

Task/Milestone 3-Sep 10-Sep 17-Sep 24-Sep 1-Oct 8-Oct 15-Oct 22-Oct 29-Oct 5-Nov 12-Nov 19-Nov 26-Nov 3-Dec 10-DecProject Initiation

Project Selection

*Project Scope

Develop Project Plan

Develop Requirements

*Preliminary Oral Report

*Preliminary Written Report

*Web Page

Initial Risk Analysis

Design & Design Analysis

Feasibility Report

*Progress Oral Reports

*Progress Written Reports

*Final Oral Report

*Final Written Report

Project Poster Judging

Member Responsibilities Chris Josh Krista

Conceptualization

x x x

Device Components

Substrate x

Drive Mechanism x

Controller Interface x

Incubator Compatibility x

Imaging Compatibility x

Calibration x

Risk Analysis

x x x

Research

Feasibility x x x

Literature Searches x

Mathematical Parameters x

Prices/Quotes x

Reports

Initializing x

Scheduling/Labor Division x

Figures x

Copy-editing x

Presentations

Preliminary x

Progress x

Final x

Client Interactions

x x

Intellectual Property

x

Website

x

References• Arnold, S. P. et. al. Design of a New Stretching Apparatus and the

Effects of Cyclic Strain and Substratum on Mouse Lung Epithelial-12 Cells. Ann Biomed Eng, 2007 35, 1156-1164

• Paten, J.A. et. al. Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs. Tis Eng, 2011 17 Part C

• Tulloch, NL. et al. Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res. 2011 Jun 4;109(1):47-59

• Ventikos et al. Modelling evolution and the evolving mechanical environment of saccular cerebral aneurysms. Biomech Model Mechanobiol 2011 10:109-132

• Zile MR. et al. Gel stretch method: A new method to measure constitutive properties of cardiac muscle cells. Am J Physiol. 1998 Jun;274(6 Pt 2):h2188-202

Questions?