Therefore, it is very difficult to manipulate a system, such as a group of cells or tissue, to behave in a desirable or optimal way without understanding the following: the effect each variable has on the system, the different possible states of each variable and how those states affect the overall system, and the relationship amongst the variables. A solution to this approach is to test all the combinations of the different stimuli and the different states of each stimulus by parallel tests. The number of test required increase exponentially with the number of stimuli. For example, the effectiveness of a six-drug combination cocktail on a tissue or cell line, which if only ten different concentration per drug is used, requires 106 or 1 million parallel tests in order to identify the optimal concentration.

INNOVATION:  The invention provides a novel way to determine the variables and the specific state of each variable that altogether exert a desirable and optimal effect on a system, such as a population of cells, without having to investigate the details of the internal process of this system (e.g., how each variable affects cellular behavior). This approach, therefore, obviates the need to run a large number of tests, thereby reducing the amount of time and resources required for this goal. Specifically, the physical device that embodies the inventive concept includes 1) a microenvironment to sustain one single cell to a population of cells, 2) a detection device to continuously detect one or more measurable cellular responses (e.g., a reporter signal), 3) instruments that provide biochemical, electrochemical, mechanical, and optical stimulation dynamically to the cell(s) and, 4) a feedback/microcontroller that regulates the stimuli based on the response detected by the detection device. The device will be supported with the appropriate software and hardware components to a) provide user-interface and data analysis b) enable automation of the optimization process.

The researchers have successfully demonstrated proof-of-concept of the inventive device by using it to study the effect of multiple external stimuli (e.g., cytokines, drugs) on the transcription factor NF-kB in a tumor cell line.

ADVANTAGES  

• The invention identifies the specific variables that yield the optimal response by stimulating the cells iteratively as opposed to conducting the large number of parallel tests that anticipate all the combination of variables, there conserving resources (e.g., cost, reagents, and samples, equipment) and time;
• The invention can be used to study impact of each variable on the system and their interdependent relationships;
• The stimulation module can be flexible to include biochemical, electrochemical, mechanical, and optical stimulation; and, the stimulation module can generate both dynamical and spatial stimulation.
  
• The overall product includes both one-time purchase products (instrument, ancillary software) and consumables (reagents, cellular microenvironment, and stimulation modules).

POTENTIAL APPLICATIONS 

• Combinatorial drug design;
• Drug screening to identify hits and to identify combination of multiple drugs;
• In vitro protein syntheses; and
• Optimization of microenvironment for cell culture and tissue engineering

Reference: UCLA Case No. 2005-246

PCT Publication Number: PCT/US05/042096