Smart Stat - An integrated optogenetic protein induction system for industrial protein and drug production

Web Published:

Smart Stat - An integrated optogenetic protein induction system for industrial protein and drug production 

Princeton Docket # 13-2838

"Smart Stat" is an integrated system which allows for real-timelight-based control of gene expression and subsequent protein production. An exogenous, highly controllable optogenetic induction system is integrated with a chemostat and robotically controlled microfluidic sampling system which allows for automated real-time imaging of cells from the steady-state chemostat culture.  Quantification of protein concentration from the images is used to feedback and control light levels, allowing for the real time adjustment of protein levels.


  • Inexpensive and easily adaptable due to use of light induction
  • Eliminates complicated media changes or long periods for chemical systems  dilute out
  • Easily amenable to any microbe of choice
  • Capable of programming variable protein concentrations over time


·         Optimization of industrial protein and drug production in cell culture bioreactors

·         Real-time monitoring of cell parameters in continuous and batch  bioreactor cultures

·         Replacement for chemical induction systems

·         Research use for interrogating genetic signaling and transcriptional networks




¹Real-time light-driven temporal control of gene expression and protein concentration in S. cerevisiae. Justin Melendez, Benjamin Oakes, Marcus Noyes, Megan N. McClean. Lewis-Sigler Institute, Princeton University, Princeton, NJ., 2012 Yeast Genetics and Molecular Biology Meeting, August 3, 2012


Biological signaling networks, like electrical circuits, take specific inputs and convert them into appropriate outputs.  Electrical engineers uncover the inner workings of such circuits by measuring the transfer function between a specific input voltage signal and output voltage.  This transfer function indicates how the electrical signal propagates through the network and allows the engineer to formulate and refine a model of the network.  Electrical input signals are created using an electronic device called a signal generator.  These devices are capable of creating arbitrary voltage waveforms such as sines, ramps, and pulses.  Additionally, signal generators can be used to control electrical circuits to produce desired outputs.

Unlike electrical engineers, biologists are very limited in the input signals they can generate to interrogate and control biological networks.  Typical experiments perturb the network with a sudden step increase in ligand and assay downstream gene expression.  Such ¿step-shock¿ inputs stimulate the biological network at the receptor level, leaving many unprobed signaling steps between input and output.  When measurement or biological noise is present, step-shocks have been theoretically shown to be inferior to time-varying inputs, such as oscillations, for identifying network components.  Overexpression of a protein of interest is often used to perturb or control a specific biological pathway, however, the inability to dynamically control the protein concentration limits the ability to adjust and control the pathway throughout time.

Biologists are in need of a "signal generator" that can create time-varying input at multiple points in a biological network.  In addition to providing a device for interrogating biological networks, a biological signal generator would allow for control of natural and synthetic biological networks used in biomedical and industrial applications.

                The "Smart Stat" uses light-based induction and real-time feedback control to produce waveforms of gene expression and protein concentration in continuous or batch cell cultures.

Light as an induction system has many advantages over chemical induction systems widely used in industry drug production today. Light induction is inexpensive costing considerably less than many chemical induction signals. Light as an induction system can be added or removed instantaneously from a large bioreactor system while chemical systems require complicated media changes or long periods for the chemical systems to dilute out. Light intensity can be adjusted to increase, decrease or change the rate of induction. In conjunction with the automated sampling system and analysis system described above, light is used to maintain protein concentration at specific levels or vary protein concentration over time.  Thus, the ¿Smart Stat¿ operates like a biological signal generator for interrogating and controlling biological networks.

Intellectual Property status

Patent protection is pending.

Commercialization Strategy

Princeton University¿s Office of Technology Licensing is looking to identify appropriate commercial partners for the further development and commercialization of this technology.


Laurie Tzodikov

Princeton University Office of Technology Licensing  (609) 258-7256

Princeton docket # 13-2838

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
Justin Melendez
Megan Mcclean
Benjamin Oakes