MerMade Oligonucleotide Synthesizer

    The MerMade is a high throughput parallel synthesizer originally designed and built at the University of Texas Southwestern Medical Center (UTSW) to support the research efforts of the McDermott Center for Human Genetics on the Human Genome Project.

    We have designed and constructed a machine which synthesizes two standard 96 well plates of oligos in a single run using standard phosphoramidite chemistry.  The machine is capable of making a combination of standard, degenerate or modified oligos in a single plate.  The run time is typically 17 hours for two plates of 20mers and a reaction scale of 20nM.  The reaction vessel is a standard polypropylene 96 well plate with a hole drilled in the bottom of each well.  The two plates are placed in separate vacuum chucks and mounted on a xy table.  Each well in turn is positioned under the appropriate reagent injection line and the reagent is injected by switching a dedicated valve.  All aspects of machine operation are controlled by a Macintosh computer which also guides the user through the startup and shutdown procedures, provides a continuous update on the status of the run and facilitates a number of service procedures which need to be carried out periodically.  Over 15,000 oligos have been synthesized for use in dye terminator sequencing reactions, polymerase chain reactions (PCR), hybridization and Reverse Transcriptase PCR.  Oligos up to 64 bases in length have been made with a coupling efficiency in excess of 99%.  These machines, working in conjunction with our oligo prediction code [Primo] are particularly well suited to application in automated high throughput genomic sequencing.

    For more information, please consult: S. Rayner, S. Brignac, R. Bumeister, Y. Belodludtsev, T. Ward, O. Grant, K. O’Brien, G.A. Evans and H.R. Garner, “MerMade:  A 2 x 96-Well Plate Oligo Synthesizer For High Throughput Production”, Genome Research, Vol. 8, 741-747, 1998. 

    The MerMade can synthesize up to 192 oligonucleotides (oligos) in two 96-well filter plates.  The synthesis uses standard phosphoramidite chemistry and solid-phase synthesis on Controlled Pore Glass (CPG) supports.  Typical synthesis is done on a 40 nmol scale.  The system consists of an XY table and a system of valves controlling liquid and gas delivery and vacuum.   The valves and XY table are controlled by a computer running UTSW designed software.   The XY table is mounted inside an outer chamber constructed of optically clear Lexan.  Argon is pumped into inner and outer chambers to provide a dry, inert atmosphere for synthesis.  Ar pressure is used to deliver the liquid reagents to the wells at each synthesis step.  House vacuum is used to transfer the liquid reagents after each synthesis step to on-board waste containment vessels.  To date, oligos synthesized by the MerMades have been used as PCR primers for genetic sequencing applications, creating DNA microarrays or "gene chips", and building artificial genes used in vaccine development. A list of recommended support equipment and supplies for the MerMade can be found by clicking here.  

    The three original MerMades were built in-house at UTSW.  After the design and building had been sufficiently developed, the fabrication of the MerMades was contracted to an outside company, Bioautomation, which currently, produces commercial models of the MerMade.  The MerMade Manual and MrOligo Control Software are available for download from this site.  

    In 1998, two commercial model MerMades were purchased to support the Department of Energy Joint Genome Institute's (JGI) sequencing efforts.  These MerMades were initially installed in October 1998 at UTSW and thoroughly tested.  After exhaustive testing, one of the MerMades was installed in the Life Sciences Division of the Los Alamos National Laboratories (LANL) in March 1999, as part of a turn-key, high throughput   oligonucleotide synthesis facility.  The second MerMade is scheduled to be installed at LANL in May 2000.  Currently, it is being used for process optimization research at UTSW.  Once in place at LANL, both MerMades will be used to produce oligonucleotides for the JGI's work on the Human Genome Project. 

    To down load the entire MerMade manual click here:  MerMade Manual

    We have recently demonstrated the ability to make Peptide Nucleic Acids on the MerMade.

    This machine is now sold by Bioautomation in Plano, TX, (972) 335-2525.  The latest tabletop version is shown below.

    The original MerMade supplied to LANL is shown below.

To down load the entire MerMade manual click here:  MerMade Manual