RE: dilution of antibody

From: gerhard nebe-von-caron (Gerhard.Nebe-von-Caron@Unilever.com)
Date: Tue Feb 29 2000 - 08:28:40 EST


Considering the concentration of 1.5ug antibody per ml to reach reasonable
staining saturation within less than 30 minutes as a ballpark figure,
this is
equivalent to 10nM of antibody. This means that in 1ml there are 10^18
molecules hopping around, or 10^12 antibodies hitting each cell if you
have a
million cells in there. One can calculate further how many antibodies are
within a certain diffusion distance of each cell to get even more
precise, but
the number of molecular involved might already help to illustrate
the funny
effects of on and off rates, depletion and mass transport
limitations. They are
also an important factor to consider when working with particle based
assays.
In general lower concentrations mean longer incubation times, so do lower
temperatures as they reduce the 'hit-rates'. If cells are unfixed that
in turn
can have effects on cell stimulation, change binding site densities....
so it
is not at all easy to decide what to do.

Regards
Gerhard

-----Original Message-----
From:	Mario Roederer [SMTP:Roederer@drmr.com]
Sent:	Friday, February 25, 2000 10:09 PM
To:	Cytometry Mailing List
Subject:	RE: dilution of antibody

Joost:

>Or am I mistaken?

You are mistaken.

Aaron Kantor and I went into this topic in some depth in our chapter
in Handbook of Experimental Immunology (5th ed) "FACS Analysis of
Leukocytes".  I recommend that you look into it for a thorough
description.

Albert was correct in his analysis--for nearly all antibodies, the
number of cells is irrelevant (until you get to numbers of 10's of
millions that bind the antibody); the concentration of the antibody,
however, is paramount.	(Incidentally, so is time and
temperature--make sure that you titrate your antibodies at the same
temperature and for the same amount of time as your experiments).

I think the reason for the origin of this error is that for a long
time, manufacturers gave their effective titres as "ug per million
cells" rather than "ug per ml".

mr

(PS:  cell number can become relevant for very high affinity
antibodies.  This is because with high affinity antibodies, the
amount of antibody supplied can be much lower, thus, in much lower
excess over antigen.  However, the vast majority of antibodies have
an affinity low enough such that a significant excess of antigen (in
typically staining experiments) is required to achieve
near-saturation.).



>Dear Albert,
>
>Sorry, but I don't agree with you. When you should look at a marker
80% of
>your cells is positive for. And you determine the amount of antibody
>(= your
>concentration) for 300.000 cells. It is not possible to get even a
>peak far
>from your negative peak when you stain 5 million cells. This means
>that you
>throw away at least 5 times the amount of antibody when you stain 300.000
>cells. Because you determined (titrated) your antibody for 5 million
>cells.
>And the definition of concentration is the amount of Ab in a certain
>volume.
>So when you got 100.000 cells and need 0.01 µg of Ab to stain them
you can
>add this in 50 µl or in 5 ml. The only difference is the timeperiod
>it will
>take to get your Ab on the cells. Or am I mistaken?
>
>Best regards,
>
>Joost Schuitemaker



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