Re: BD LSR ?

From: David Coder (dcoder@u.washington.edu)
Date: Tue Mar 07 2000 - 13:35:15 EST


Having had one of the first LSR analyzers installed in the field, my experience
parallels that noted below. For examples of data (4 color surface markers, DAPI
and 3 color, DNA (DAPI) linearity checks, and calcium flux comparisons with the
Vantage see the LSR lab web page:
http://nucleus.immunol.washington.edu/Research_facilities/Lsr1/lsr.htm

Note that the DAPI and 3 surface marker illustrations are from an 8-parameter
data file. For a user-operated instrument, it is quite easy to set complex
analytical procedures. Once defined, protocols, screen layouts, instrument
configuration, and all instrument settings are easily retrieved from CellQuest
disk files.

There is no instrument alignment to be done. In fact, the optical stability has
been boringly invariant. Allow about 30 minutes warm-up time if using the HeCd
laser, and then retrieve your experimental setup and run samples. So, if anyone
is familiar with a FACScan and CellQuest, then multi-color experiments on the
LSR should be easy to run.

Fluorochromes that have been used successfully include: FITC, PE, PE-Texas Red,
PE-Cy5, PE-Cy7, PerCP, CSFE, GFP, DAPI, Hoechst 33342, PI, 7-AAD, and indo-1.

Calcium flux experiments using indo-1 have been quite successful. As I note on
the above web page, the resolution of populations showing different levels of
calcium flux seems to be better on the LSR than the Vantage. In fact, the
shorter calcium-bound fluorescence of indo-1 is better resolved on the LSR than
the Vantage since calcium-bound indo-1 is excited more efficiently with the
325nm light of HeCd laser. On the other hand, the calcium-free indo-1
fluorescence is better resolved when excited with the longer wavelength uv lines
of the argon laser.  (I built a very cheap and simple water jacket to maintain
samples at 37C. It consists of a 15mm diameter polypropylene test tube cut to a
height to take a standard 13mm sample tube, and wound with two concentric layers
of about ~3mm silicon tubing; electrical tape keeps the tubing windings in
place. The ends of the tubing are connected to a recirculating 37C water bath.
There is sufficient clearance for the sample arm to support the water jacket and
sample tube.  It's very easy to remove the sample, add agonist, and replace the
sample tube. Note that the gap on the time vs. indo-1 ratio density plot is
shorter on the LSR than on the Vantage.)

As Dr. Petrie notes, it keeps the Vantage doing high-speed sorts, plate sorts,
and 6 to 8 color analysis as it should be.

If all goes well (still waiting for some filters to arrive), the HeNe laser I
installed on the LSR may give us the ability to do DNA and 6 other colors in
addition to pulse processing. Stay tuned . . . .

Dave
**********************************
David M. Coder, Ph.D.
Director, Cell Analysis Facility
Dept. of Immunology
Univ. of Washington School Medicine
Box 357650
Seattle WA 98195-7650

tel. 206-685-3014
fax. 206-543-3480
email: dcoder@u.washington.edu
----- Original Message -----
From: Dr. Howard Petrie <h-petrie@SKI.MSKCC.org>
To: cyto-inbox
Sent: Friday, March 03, 2000 12:32 PM
Subject: re: BD LSR ?



I didn't see anyone else respond to Franck Morel's query about the B-D LSR,
so I'll put my two cents in.  Having been tied to a sorter for UV
applications for the last decade (a shameful misuse of both sorter  and
sorter-operator [i.e., my] time), all I can say is that it's about time.
We have had our instrument for about 3-4 months, and at times (see below)
the data have been incredibly good, with DNA cv's of 3-5% and no
discernable noise (HeCd lasers must have improved significantly).  We
routinely perform 3-4 color surface/cytoplasmic immunfluorescence together
with DNA (UV) analysis.  On the sorter, we used DAPI, FITC, PE, Texas Red,
and APC.  On the LSR, we presently use DAPI, FITC, PE, Red-613, and PerCP
(we have the UV/488 model).  When the red laser is available/installed, we
will be able to use DAPI/FITC/PE/PerCP/APC (a combination we presently use,
sans DAPI, on the Calibur), and most remarkably about this combination, the
only compensations are FITC/PE.  Needless to say, given this and the
absence of daily alignment, everyone in my lab is able to do experiments
without the need for me to be there, which represents a major increase in
productivity, not to mention freeing up the sorter for what it is intended
to do.  Calcium flux experiments have also been almost trivial to set up;
although the people doing this (from other labs) have not actually SEEN
flux, I think this is a biological problem, because the baseline looks
quite normal.

On the cautionary side, on three occasions we have experienced significant
deterioration of laser alignment (to give credit where due, B-D has always
responded by sending an engineer within 24-48 hours).  The source of the
problem has been difficult to pinpoint, and may be due to the instrument
getting settled in, or may have a more deep-rooted source, only time will
tell.  Right now I can say that it's been a major improvement for us, and
assuming that the stability problems are worked out, I think it's going to
be an extremely powerful resource, as well as freeing up sorters for
sorting.

In my opinion, the usefulness of this instrument, either in 2 laser
(UV/488) or 3 laser form is dramatically enhanced by the ability to use
PerCP, given the simplicity of compensation mentioned above.  Of course,
this is limited by B-D/PharMingen's willingness to conjugate antibodies to
PerCP (hint)...

It is true that this instrument is NOT inexpensive, but I think that when
you balance the lack of need for an operator and the time that is made
available on the sorter, it becomes justifiable.



Howard T. Petrie, Ph.D.
Head, Developmental Immunology Laboratory
Director, Monoclonal Antibody Core Facility
Memorial Sloan-Kettering Cancer Center
Box 341, 1275 York Avenue
New York, NY 10021
phone (212)639-2149
fax (212)794-4019



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