Re[2]: APC/PE

From: Tom Frey (Tom_Frey@bdis.com)
Date: Mon Dec 01 1997 - 19:33:27 EST


Gene Pizzo asked:

>>>>I'll ask the question again...it hasn't been answered here yet, twice.
>>>>It wasn't answered in BD class when I asked it.
>>>>It wasn't answered by the service engineers I've asked.
>>>>Maybe no one has an answer.

Well, I feel kind of compelled to put in my two cents now!  Unfortunately, I
also feel an urge to the longwinded today - you are warned.

>>>>We all understand that the Cy5 of the PE-Cy5 tandem can be excited
>>>>by the red laser, that's the easy part. But if the signal generated 
>>>>from the two beams is separated in both space and time why should
>>>>there be a compensation necessity?

Compensation is used to remove the true fluorescence of a dye from channels that
we don't want it to show up in, so that we can then assign one antibody to one
channel.  (For example fluorescein REALLY emits in FL2 at 585 nm, we just comp
it away) PerCP and PE/Cy5 are each excited by the red and the blue lasers and
emit long wavelength red.  The separation of the beams is what allows us to tell
whether the emission is from red excition or from blue excitation. Since both
PerCP and PE/Cy5 are "FL3 dyes" we want to subtract their red excited
fluorescence from the FL4 channel.

>>>>Furthermore, why on the FACSCalibur is it necessary to align the two 
>>>>beams in time when on the FACStar Plus the electronic separation of 
>>>>the two beams in time is considered a necessity?

For those you who haven't used a four color Calibur, I think we're discussing
the Time-Delay Calibration function that is part of the Calibur.  This function
does NOT align the beams in time.  It (more or less) matches the timing between
pulses from the two beams in the electronics to the travel time between the two
beam intercepts.  It is intended to allow for changes in the particle velocity
in the sample stream.

The pulse from the red beam is delayed to arrive simultaneous with the pulses
from the blue beam.  The delayed signal is used for interbeam compensation.  The
Calibur does this compensation in analog, the pulses are subtracted over the
entire pulse waveform.  (I don't want to get into an argument about whether this
is "best" - there are good reasons to do things this way in a 10-bit system (and
no I don't know where bit came from))  For analog compensation between beams the
pulses from the two sources need to be properly aligned - ie the peaks need to
occur at the same time.  If, during time delay calibration, the system senses a
misalignment of the pulse originating from the blue laser (forward scatter in
this case) and that from the red laser (FL4 from the recommended APC beads) then
the electronics are adjusted so that the pulse alignment is corrected so that
accurate subtraction can occur.

I hope this goes some distance to answering the original question without
inducing too many blank stares.  I am sure, as always, the group will clarify
any points they feel are incorrect or too vague.



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