BMSEED
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In Vitro Research

In Vitro Research

MicroElectrode Array Stretching Stimulating und Recording Equipment

(MEASSuRE)

Cells in the body are constantly subject to mechanical forces, with yet poorly understood effects on cell division, gene expression, cell migration, morpho-genesis, ion channel gating, and others. In a physiological stretch, the cells are stretched within their healthy limits. It is currently difficult to investigate reproducibly and reliably the effects of physiological and pathological mechanical stretch on the electrophysiology of biological tissue, both in vitro and in vivo, because current electrodes are hard and stiff, thus break or damage the tissue upon stretching. Moreover, existing commercial technologies only allow to either stretch cells mechanically or to stimulate them electrically, but not both. 

MEASSuRE solves this problem by incorporating BMSEED’s proprietary elastically stretchable microelectrodes. MEASSuRE reproduces the mechanical and electrical in vivo environment in a controlled environment in vitro by allowing the application of a controlled stretch (strain, strain rate) to a cell or tissue culture while simultaneously stimulating electrophysiolgical activity to assess the health of the cells.

MEASSuRE

Capabilities

  • Mechanical stretching
  • Radial and uniaxial
  • Optical imaging
  • Fluorescence
  • Electrical recording
  • Electrical stimulation
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Capabilities of MEASSuRE

MEASSuRE is a complete solution for researchers to stretch cells/tissue mechanically, image them optically, and record/stimulate electrophysiological activity, separately or concurrently. 

Mechanical stretching 

  • radially or uniaxially
  • once or cyclically
  • up to 50% strain
  • at strain rates of up to 100s-1
  • virtually any stretch pattern can be programmed with macros
  • high reproducibility

Optical imaging

  • before, during and after stretching
  • up to 1700 frames per second at 2MP resolution
  • custom, easy-to-use BMSEED software to independently verify the tissue strain

Electrophysiology

  • electrodes stretch with the cells/tissue
  • recording/stimulation before, during, and after stretching
  • comparison of pre and post stretch electrophysiological activity (normalization)
  • soft MEAs on elastomeric silicone substrates
  • standard MEAs on rigid substrates available

Applications for MEASSuRE

Potential applications for MEASSuRE can be grouped in the following segments: 

Physiological Stretching of Cells

Tissue Engineering
Stem cells that differentiate into a specific tissue have properties that resemble adult tissue more closely when the cells are under mechanical and electrical stimulation during the differentiation process. MEASSuRE has the capability to provide both, electrical and mechanical stimulation. 

Drug Toxicity Testing
Tissues grown from stem cells differentiated under mechanical and electrical stimulation are more representative of their respective organ in an adult human. Thus, the validity of drug toxicity testing by pharmaceutical company increases. MEASSuRE has the capability to provide both, electrical and mechanical stimulation.

Mechano-Biology
There are a variety of mechanisms for transducing and sensing mechanical forces in neurons and other cell types. MEASSuRE provides capabilities to fundamentally understand the effect of mechanical forces.

Pathological Stretching of Cells

Neurotrauma Research and Treatments
MEASSuRE allows to reproduce reliably and repeatedly the biomechanics of traumatic brain injury and spinal cord injury in a controlled environment.  Changes in the electrophysiology of the injured neurons can be assessed in a straightforward manner with the embedded microelectrodes by comparing the post-injury electrophysiology to pre-injury level. The effectiveness of drugs or other treatment strategies to minimize the damage after injury cantherefore be readily assessed.

Concussion research
MEASSuRE will allow researchers and physicians to develop improved concussion protocols that are based on the electrophysiology of the underlying injury rather than cognitive tests. 

Muscle Injury Research and Treatments
MEASSuRE will allow the investigation of the mechanism of those muscle injuries that are caused by excessive tension or compression, and the evaluation of drugs to speed up recovery. 

Mechanisms on Stem Cell Repair Research
Stem cells are involved in repair processes after injury in different parts of the body, e.g., in the brain after a traumatic brain injury. The mechanism of the activation of the mechanoreceptors is not understood. MEASSuRE will be a useful tool to elucidate and study this mechanism.

Other – Research on Neurodegenerative Diseases
Neurodegenerative diseases such as Alzheimer’s disease have common pathological pathways with traumatic brain injury, e.g., the build-up of amyloid-plaques. Therefore, MEASSuRE might be a valuable tool for the early evaluation of the efficacy of drug candidates against Alzheimer’s disease.

 

How is the mechanical stretch applied to the cells?

Morrison et al., J Neurosience Methods, 150:192, 2006

Schematic drawing of the stretching mechanism:
The tissue is stretched by pulling the sMEA over a cylindrical indenter.

 

One cycle of stretching followed by relaxation

Before Stretching: The microelectrodes record signals from the tissue.

During Stretching: The tissue, the microelectrodes, and the silicone membrane are stretched. The microelectrodes record  signals from the same location on the  tissue as before stretching. 

After Relaxation: The tissue, the microelectrodes, and the silicone membrane are relaxed. The microelectrodes record/stimulate signals at the same tissue/cell location before and during stretching. 

Can be repeated over many cycles