RE: dilution of antibody

From: gerhard nebe-von-caron (Gerhard.Nebe-von-Caron@Unilever.com)
Date: Wed Mar 01 2000 - 05:01:53 EST


Whilst eventually my email seems to be unscrambled, my math hasn't as I
couldn't read my own scribble and turned my 10^20 into 10^26(thanks mario).
The excess is not that high as 10nM are actually 6* 10^12 molecules which makes
it 6*10^6 per cell. That leaves a 120 fold excess on and average cell with
50000 epitopes to be covered.  Still a lot of molecules but makes it look less
funny but more realistic.
regards
Gerhard
-----Original Message-----
From:	gerhard nebe-von-caron [SMTP:Gerhard.Nebe-von-Caron@unilever.com]
Sent:	Tuesday, February 29, 2000 1:29 PM
To:	Cytometry Mailing List
Subject:	RE: dilution of antibody



Considering the concentration of 1.5ug antibody per ml to reachreasonable
staining saturation within less than 30 minutes as a ballparkfigure, this is
equivalent to 10nM of antibody. This means that in 1mlthere are 10^18 molecules
hopping around, or 10^12 antibodies hittingeach cell if you have a million
cells in there. One can calculatefurther how many antibodies are within a
certain diffusion distance ofeach cell to get even more precise, but the number
of molecular involvedmight already help to illustrate the funny effects of on
and off rates,depletion and mass transport limitations. They are also an
importantfactor to consider when working with particle based assays.
In general lower concentrations mean longer incubation times, so dolower
temperatures as they reduce the 'hit-rates'. If cells are unfixedthat in turn
can have effects on cell stimulation, change binding sitedensities....	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 stain300.000
>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 thetimeperiod
>it will
>take to get your Ab on the cells. Or am I mistaken?
>
>Best regards,
>
>Joost Schuitemaker



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