Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Patent
1992-03-19
1993-12-28
Housel, James C.
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
422100, 436809, 435310, 435311, 435313, B01L 1100
Patent
active
052737187
DESCRIPTION:
BRIEF SUMMARY
The present invention is related to automation of biochemical reactions, and more particularly to the treatment of a plurality of samples in microtiter plates or similar processing plates in molecular biological methods.
Molecular biology is a rapidly growing field of science but since it is a fairly young discipline a great number of basic methods are still done manually, or at best semi-automatically. This being the case in spite of the fact that many of the procedures utilized are based on handling a great number of samples, in a lot of repetitive steps. Examples of such methods include isolation of RNA, chromosomal DNA or DNA from plasmids or other vectors, restriction enzyme digestion of DNA, sequencing of DNA, elongation and polymerization of DNA by enzymes, oligonucleotide synthesis, construction of various vectors and gene libraries in microorganisms, screening of bacterial strains for biologically active clones, etc, etc. Each method of this type involves frequent manual handling of samples like for instance by the transfer of liquids between containers by pipetting, mixing, centrifugation, incubation, washing and precipitation, just to mention a few procedures.
Another general characteristic of methods in molecular biology is that some of the reagents are available only in small amounts or are very expensive, and therefore in most cases only very small volumes, usually in the .mu.l range, of reagents and reaction mixtures are handled in each step of such a method. The reagents or other compounds in the reaction mixtures are moreover often sensitive and therefore special precautions considering temperatures, mechanical sheering, etc, are required. Some of the methods further comprise the handling of potentially hazardous compounds.
Experimental work in molecular biology is accordingly very time consuming and labor intensive. The need for automation can be further illustrated with an example of single-stranded template preparation and DNA sequencing, according to a method described in Current Protocols in Molecular Biology, Ed. F. M. Ausbel.
So far automation in molecular biology has mainly been purification and sequencing chemistry have been automated with laboratory robotic equipments essentially automating the same procedures as they are performed manually Examples of such equipments are: Beckman Biomek 1000 and the Zymark robotic system. Although these robots have certain advantages over the manual methods there are still many drawbacks Firstly, a lot of consumables are used like for instance a new pipette tip for every liquid manipulation. Secondly, the systems are general laboratory robots and fairly complicated to use and to reprogram. Thirdly, a lot of manual work has to be carried out before as well as after the robot has been processing a part of the complete method. Sometimes a program has to be interrupted in the middle of a run and sample manually taken out for a centrifugation or incubation step. These drawbacks together with the high cost of a laboratory robot makes it far from ideal in a molecular biology laboratory.
Microtiter plates, which are trays having a number of separate reaction wells with openings on one side (the upper side) of the tray, are often used for carrying out the manual type of procedures discussed above, since a number of experiments can be carried out in parallel. Samples, liquids etc are introduced into said wells and subjected to the various procedures of the particular method. In one type of microtiter plates there is also an outlet from each well at the bottom side of the plate through which liquid can be drained from the well to a waste, for instance by suction. This outlet can be open, but preferably it contains a porous membrane for retaining particles or precipitates in the well, depending on the type of method to be carried out. A microtiter well can also be packed with a matrix for chromatographic separation of various constituents in a sample. Such matrices are mainly of the type in which components are retained by binding due to electrostatic inter
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Andersson Kent
Skold Sven-Erik
Housel James C.
Pharmacia LKB Biotechnology AB
Philpitt Fred
Wallenhorst Maureen M.
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