Cell based shear stress sensor

A method of evaluating a biotechnological device or system with respect to fluid shear stress acting on cells caused by operation of said biotechnological device or system, comprising the steps of:

• (a) providing a biotechnological device or system, (b) subjecting a sample comprising said cells to operation of said biotechnological device or system, wherein said cells comprise an isolated nucleic acid molecule or a nucleic acid vector comprising said isolated nucleic acid molecule, and wherein said isolated nucleic acid molecule comprises a functional mammalian EGR-1 (early growth response protein 1) promoter region that is operatively linked to a gene encoding a fluorescent protein and controls expression of said gene;
• (c) measuring an intensity of a fluorescence signal emitted by the fluorescent protein in the sample of said cells;
• (d) measuring an intensity of a fluorescence signal emitted by the fluorescent protein in a control comprising said cells but not subjected to the operation of the biotechnological device or system;
• (e) determining a level of fluid shear stress acting on said cells during operation of said biotechnological device or system by normalizing the intensity of the fluorescence signal measured in step (c) by the intensity of the fluorescence signal measured in step (d);
• and (f) determining whether the biotechnological device or system applies an acceptable level of fluid shear stress to said cells based on whether the level of fluid shear stress determined in step (e) is below a predetermined level of fluid shear stress.

A method of designing a biotechnological device or system, comprising the steps of:

• (a) providing a candidate biotechnological device or system, (b) subjecting a sample comprising cells to operation of said candidate biotechnological device or system, wherein said cells comprise an
• isolated nucleic acid molecule or a nucleic acid vector comprising said isolated nucleic acid molecule, and wherein said isolated nucleic acid molecule comprises a functional mammalian EGR-1 (early growth response protein 1) promoter region that is operatively linked to a gene encoding a fluorescent protein and controls expression of said gene;
• (c) measuring an intensity of a fluorescence signal emitted by the fluorescent protein in the sample of said cells;
• (d) measuring an intensity of a fluorescence signal emitted by the fluorescent protein in a control comprising said cells but not subjected to the operation of the biotechnological device or system;
• (e) determining a level of fluid shear stress acting on cells during operation of said candidate biotechnological device or system by normalizing the intensity of the fluorescence signal measured in step (c) by the intensity of the fluorescence signal measured in step (d);
• (f) determining whether the level of fluid shear stress acting on said cells during operation of said candidate biotechnological device or system is higher than a predetermined level of fluid shear stress, (g) based on the determination of step (f), either:
• (i) accepting the design of the biotechnological device or system as the final design of the biotechnological device or system, or (ii) modifying the design of the candidate biotechnological device or system to apply less shear stress to cells and repeating steps (a) to (e) until the level of fluid shear stress determined in step (c) is lower than said predetermined level of fluid shear stress, wherein upon each repetition of steps (a) to (e), the candidate biotechnological device or system used in step (a) uses the previously modified biotechnological device or system design.