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I would like to control a large number (hundreds) of GPIO ports with a Rapberry Pi for high voltage applications such as controlling Nixie tubes (but this woulbe be applicable to any kind of GPIO control).

What is the easiest way one might achieve that?

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One simple way to achieve that is by using a MCP23008 (8-bit) or an MCP23017 (16-bit) I2C GPIO expansion chips. The Raspberry Pi has one I2C bus and the CP23008/MCP23017’s have a 3-bit address select port, so in-theory you can connect up 8 MCP23008/MCP23017’s giving you a GPIO capability of an additional 128 IO pins using these devices (http://wiringpi.com/extensions/i2c-mcp23008-mcp23017/).

To further enable control of high voltage (low power) devices such as Nixie Tubes, one can use MPSA42 NPN transistors, which are rated up to 300V, way above the ignition voltage of most Nixie tubes.

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