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15 Assessment of Vitamin D Status in the 21 Century 331
This modification finally made mass assessment of circulating 25(OH)D possible.
In that same year this assay became the first FDA-approved device for the clinical
diagnosis of nutritional vitamin D deficiency. Further, during these past 23 years,
these DiaSorin tests have been utilized in the vast majority of large clinical studies
worldwide to define “normal” circulating 25(OH)D levels in a variety of disease
states. This test still remains today the only RIA-based assay that provides a “total”
25(OH)D value.

15.3.3 Random-Access Automated Instrumentation

DiaSorin Corporation, Roche Diagnostics, and the now defunct Nichols Institute
Diagnostics all introduced methods for the direct (no extraction) quantitative deter-
mination of 25(OH)D in serum or plasma using competitive protein assay chemilu-
minescence technology [15]. These assays appear quite similar on the surface but
they are not.
In 2001, Nichols Diagnostics introduced the fully automated chemilumines-
cence Advantage® 25(OH)D assay system. In this assay system, non-extracted
serum or plasma was added directly into a mixture containing human DBP, acridin-
ium-ester labeled anti-DBP, and 25(OH)D -coated magnetic particles. Note that the
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primary binding agent was human DBP. Thus, this assay was a CPBA, much like
the manual procedure introduced in 1974 by Belsey et al. [9]. The major difference
between these procedures was that Belsey depotenized the sample with ethanol
before assaying it. The calibrators for the Belsey assay were in ethanol. In the
Advantage assay, the calibrators were in a serum-based matrix, and its developers
assumed that this matrix would replicate the serum or plasma sample introduced
directly into the assay system. In the end, the 1974 Belsey assay never worked and
neither did the Advantage 25(OH)D Assay. The company removed the assay from
the market in 2006.
In 2004, the DiaSorin Corporation introduced the fully automated chemilumi-
nescence Liaison® 25(OH)D Assay System [15]. This assay is very similar to the
late Advantage assay, with one major difference – the Liaison assay uses an anti-
body as a primary binding agent as opposed to the human DBP in the Advantage
system. Thus, the Liaison is a true RIA method. Details on this procedure are avail-
able elsewhere [15]. The Liaison 25(OH)D assay is co-specific for 25(OH)D and
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25(OH)D , so it reports a “total” 25(OH)D concentration. DiaSorin recently intro-
3
duced a second-generation Liaison 25(OH)D assay. This new version has increased
functional sensitivity and much improved assay precision. The Liaison 25(OH)D
assay is the single most widely used 25(OH)D assay in the world for clinical
diagnosis.
The most recent addition to the automated 25(OH)D assay platforms is from
Roche Diagnostics. Their test is an RIA called vitamin D (25-OH) and it can be
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performed on their Elecsys and Cobas systems. Roche only released this assay in
2007, so very little information on it is available. However, the assay can only