What about just using a file event callback? Something like:

$widget->fileevent($fh, 'readable' => sub { ...call-back code... });
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In the call-back code you can directly interact with other widgets - e.g. change the text of a widget, etc.

Also, since you are accessing the serial port as /dev/ttyS0, you should just be able to open and read/write to it directly just like any other file object:

open(S, '+<', '/dev/ttyS0');
read(S, $buf, 1024, length($buf));
print S "etc.\n";
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The Device::SerialPort module is still useful for configuring the port, but it's not needed to read/write to it. One additional configuration you might want to use it to put the port into 'raw' mode instead of line-buffered mode. To be honest, I'm not really sure how it's done with Device::SerialPort -- I've always used the old-school system("stty -F /dev/ttyS0 raw"). :-)

Finally, I haven't tried it, but judging from this example code, file event call-backs should work even in a Win32 environment.

Update: Have a look at this page for an example of the fileevent call-back (under 'Executing Nonblocking System Commands') The code reads from a pipe, but the principle is the same with a serial port.