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ABSTRACT:
A
new class of magnet plates has recently been developed at
the Joint Genome Institute and Lawrence Berkeley National
Laboratory (JGI/LBNL) for high-throughput purification
of biological samples in high-density 384-well microtiter
plates. This technology is applicable to emerging fields such
as functional genomics, proteomics and immunological drug
screening since it can selectively separate proteins and DNA
from various contaminates based solely on a magnetic field.
These plates are ideal for any process that requires automated
bead manipulation in high-density microtiter plates containing
sample volumes as low as 3 ul.
The
magnetic structure is a novel hybrid of permanent magnet and
ferromagnetic materials that produces magnetic fields significantly
higher than those of any commercially available magnetic plate.
These hybrid magnet plates are in constant production use
at the Joint Genome Institute and enabled the integration
of a new rolling circle amplification process that reduced
labor costs by 30% with a concurrent increase in process reliability
[see publication]. This new sequencing process has achieved
unprecedented production pass rates that typically exceed
92% with read lengths well above 630 phred-20 bases.
The hybrid magnetic plates are designed to be compatible with
industry standard microtiter plate formats including 96, 384
and 1536 well plates. They may also be used for separation
processes in unpartitioned containers.
Performance
Comparison:
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| Figure 1: Field strength comparison of five magnet plates at magnet surface. Click on the image for a bigger picture. |
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| Figure 2: Field strength comparison at 1 cm above magnet. Click on the image for a bigger picture. |
Relative
field strengths of five different magnet plates are shown
in figures 1 and 2. Three of the magnet plates (with “LBNL” designation) were developed at JGI/LBNL. The other two magnet
plates are commercially available models.
The
field strengths were measured at two heights: a) less than
0.5 mm above the magnet surface, and b) at 1 cm above the
magnet surface. Measurements were made using a Hall effect
probe. As shown in figure 1, the hybrid magnetic structure
produces fields at the magnet surface that are 70% greater
than the best performing of the industry 384-well magnet plates
tested. When compared to the most commonly used commercial
96-well magnet plate, the performance differential is more
dramatic. The maximum fields of the hybrid are approximately
340% greater.
More
importantly, as shown in figure 2, the fields at a distance
of 1 cm above the magnet are more than 400% stronger than
those of the 384-well commercial magnet and more than 1000%
stronger than the fields of the 96-well commercial magnet.
Thus, the range of the fields above the hybrid magnet plates
is significantly greater than that of available commercial
magnet plates. This aspect of the hybrid allows it to exert
a much stronger force on magnetized entities that are higher
above the magnetic structure, e.g., magnetized DNA or proteins
that are in the upper reaches of the liquid samples in the
microtiter plate wells.
The
higher magnetic fields of the hybrid structures result in
greater holding forces on magnetized entities that are being
processed. This allows for more vigorous washing and sample
volume recovery. The magnetized entities are also drawn out
of solution with a higher yield and at a faster rate. Current
development versions of these hybrid plates have exhibited
maximum fields in excess of 9000.0 Gauss. In addition, the
current design is easily modified to produce fields well above
1.0 tesla or 10000.0 gauss.
Gradient
distributions:
The
gradient distributions of these hybrid structures can be controlled
and shaped to produce finely structured vertical and horizontal
gradients with corresponding directional forces. This allows
for magnetized entities to be held at user-defined positions
in the microtiter plate wells for more effective separation
and extraction.
General
attributes:
These
hybrid structures are energized by permanent magnets and require
no external power source. They are compact, with a footprint
slightly larger than a standard microtiter plate and a thickness
of approximately 1 inch. They have been adapted for use with
most commercially available microtiter plates. They have also
been adapted for use on liquid handling robots and other automated
devices including the 96 and 384-channel Hydra dispensers
(Robbins Scientific, Sunnyvale, CA). In addition, fabrication
techniques have been developed that allow for production of
these structures in large numbers at affordable prices.
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