APPLICATION OF TECHNOLOGY:

Hybrid Magnet Plate and 384-Well Microtiter Plate

• Functional genomics
• Genetic sequencing
• Proteomics
• Immunological drug screening
• Automated DNA purification
• Automated protein purification
• Any magnetic bead based purification method
• Industrial flow separation techniques
• Microarrays

ADVANTAGES:

• Produces fields that are 70% stronger than those of the best commercial magnet plates resulting in higher sample yields and faster processing times
• Compatible with most 96, 384 and 1536-well standard microtiter plates
• Extended field range that increases the usable sample and wash volumes
• Reduces labor costs and increases reliability
• Validated in a high-throughput sequencing facility with 92+% of samples producing more than 630 phred-20 base

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:

Figure 1: Field strength comparison of five magnet plates at magnet surface. Click on the image for a bigger picture.

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.

STATUS:

• Available for licensing.
• U.S. Patents #6,954,128; 7,148,778 and 7,486,166 available at www.uspto.gov.

REFERENCE NUMBER: IB-1714

PUBLICATIONS:

David Humphries, et al, New High Performance Hybrid Magnet Plates for DNA Separation and Bio-Technology Applications, D.O.E. Joint Genome Institute and Lawrence Berkeley National Laboratory, Berkeley, California, 2001.

C. Elkin, H. Kapur, T. Smith, D. Humphries, M. Pollard, N. Hammon, and T. Hawkins, “Magnetic Bead Purification of Labeled DNA Fragments for High Throughput Capillary Electrophoresis Sequencing,” Biotechniques, Vol 32, No. 6, June 2002, pp 1296-1302.