RE: Cell Sizes, FSC, and SSC

From: Robert C. Leif (rleif@rleif.com)
Date: Mon Jul 01 2002 - 20:09:17 EST


From: Bob Leif
To: cyto-inbox
Howard wrote, " And, as far as sizing goes, while Coulter volume has its
problems, it's far more accurate than scatter measurements."

I agree that Coulter volume is far more accurate than scatter
measurements. However, this statement should include the modifier than
scatter measurements made with today's commercial flow cytometers. A
major problem with low angle light scatter is that the optics have been
optimized for the fluorescence measurements. The cone angle is too big.
Al Brunsting made rather precise bulk static light scatter measurements,
years ago at Los Alamos. Frank et al. (1) were able to measure the
length to width ratio of erythrocytes. Although this work was based on
my idea, the vast majority of it was done after I left Coulter.

Coulter volume is both precise and has only two problems: 1) For most
cells, the orifice should be 70 to 100 microns. 2) Even though the late
Mack Fulwyler made it work for a sorter, there is a significant problem
concerning the location of the second Coulter electrode in a sorter,
particularly in a system that requires a high numerical aperture
fluorescence optical detection system. The problem of the gas bubbles
produced at the electrodes was solved years ago (2,3).

The use of the combination of Coulter DC and AC impedance and median
angle (45 degree) light scatter does produce good discrimination among
leukocytes in the Beckman Coulter hematology analyzers. It also works
with fluorescence (4).

1) Apparatus and Method for Determination of Individual Red Blood Cell
Shape Coulter Corp., R. S. Frank, J. L. Wyatt, W. Gong, C. M. Rodriguez,
and R. C. Leif. 5,798,827 (1998).

2) Use of Fluid Retarding Ion Conducting Material, Coulter Electronics,
Inc., R. C. Leif, 4,258,316 (1981).

3) R. C. Leif, V. Guarino and N. Lefkove; "The AMAC IIA, A True Bridge
Circuit Coulter-Type Electronic Cell Volume Transducer". J. Histochem.
Cytochem. 27, pp. 225-233 (1979).

4) R. C. Leif, M. L. Cayer, W. Dailey, T. Stribling, and K. Gordon, "The
use of a Spherical Multiparameter Transducer for Flow Cytometry".
Cytometry 20, pp 185-190 (1995).

-----Original Message-----
From: Howard Shapiro [mailto:hms@shapirolab.com]
Sent: Sunday, June 30, 2002 5:12 PM
To: cyto-inbox
Subject: Cell Sizes, FSC, and SSC


Annette Byrne wrote:

 > Hello all
 >
 > Does anyone have an info on relative sizes of the following cell
types:
 > Fibroblasts, endothelial cells, smooth muscle cells and macrophages.
I am
 > trying to make a gross distintion of a mixed cell population
containing the
 > cells above based on their FSC/SSC.
 >
 > If anyone could order them based on largest to smallest cell type I
would
 > be eternally grateful !
 >

FSC does not measure cell size!!!!!!!! In some instruments, 5.5 um
plastic
beads have bigger FSC signals than 5.0 um plastic beads (and in other
instruments, they don't).  These beads are relatively uniform and
smooth-surfaced and spherical, and all have pretty much the same
refractive
index; FSC (and SSC) signals are influenced by both size and refractive
index. The refractive indices of cells, by contrast, vary with the
cells'
content of water and of proteins and other macromolecules. If you can't
reliably use FSC to tell that a large lymphocyte is bigger than a small
one, you certainly can't use FSC to compare relative sizes of different
cell types. If you happened to have access to pure populations of the
cell
types you were interested in, you could produce FSC vs. SSC plots for
each,
which might help in resolving a mixture, provided the cells in the
mixture
had not been exposed to conditions that could change their refractive
indices or sizes.

The best way to identify mixed cell types on FSC vs. SSC plots is to
gate
individual cell types based on the presence of a specific marker, but
you
have to be sure of the marker specificity - see my reply to a posting
from
Ray Hester on reticulocytes.

And, as far as sizing goes, while Coulter volume has its problems, it's
far
more accurate than scatter measurements.

-Howard



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