Cell line, system and method for optical-based screening of ion-channel modulators
A variety of applications, systems, methods and constructs are implemented for use in connection with screening of ion-channel modulators. Consistent with one such system, drug candidates are screened to identify their effects on cell membrane ion channels and pumps. The system includes screening cells having light responsive membrane ion switches, voltage-gated ion switches and fluorescence producing voltage sensors. A chemical delivery device introduces the drug candidates to be screened. An optical delivery device activates the light responsive ion switches. An optical sensor monitors fluorescence produced by the voltage sensors. A processor processes data received from the optical sensor. A memory stores the data received from the optical sensor.
1. A system for screening drug candidates to identify their effects on cell membrane ion channels and pumps, the system comprising:
a genetically modified mammalian cell, wherein the cell is genetically modified to express a heterologous, microbial light-responsive ChR2 ion channel and a heterologous, microbial light-responsive NpHR ion pump, wherein the cell comprises a voltage-gated ion channel and a fluorescence producing voltage sensor;
a chemical delivery device for introducing the drug candidates to be screened;
an optical delivery device to activate the light responsive ion switches; and
an optical sensor to monitor fluorescence produced by the voltage sensors.
2. The system of claim 1 , wherein the voltage-gated ion channel is a Ca2 + channel.
3. The system of claim 1 , wherein the cell further comprises an indicator.
4. The system of claim 1 , further comprising an array of wells each containing a portion of the screening cells and an array of optical sensors for detecting light from respective wells from the array of wells.
5. The system of claim 1 , further comprising a processor to process data received from the optical sensor.
6. The system of claim 1 , further comprising memory for storing the data received from the optical sensor.
7. The system of claim 3 , wherein the indicator is a calcium indicator.