Sampler transfer

Details Sampler transfer Sampler transfer

1999-07-09

2002-08-06

Warden, Jill (Department: 1743)

Chemistry: electrical and wave energy

Processes and products

Electrophoresis or electro-osmosis processes and electrolyte...

C204S456000, C204S467000, C204S606000, C204S616000, C435S287700, C435S309100, C422S105000

Reexamination Certificate

active

06428668

ABSTRACT:

DESCRIPTION
The invention relates to a method for moving a sample substance by a sample feeder from a sample pickup site to a sample delivery site of a sample processor, preferably a sample analyzer.
In a known procedure (German patent document A1 38 05 808, FIGS. 10, 11), the sample substance is withdrawn by a pipetting system from a sample-vial rack and moved to the sample processor in the form of a vertically oriented electrophoresis apparatus. Moreover several samples may be picked up simultaneously using a corresponding number of pipets and be fed into corresponding sample wells at the upper gel edge. This known sample feeder system is mechanically highly complex, the more so when very thin gel layers are being used and at the same time a large number of samples must be analyzed. The gap between the glass plates subtended by the gel thickness presently is less than a mm for the desired gel thicknesses; the separation between consecutive sample sockets is a few mm. Depending on gel width, up to 100 sample wells may be arrayed adjacently. The complexity is correspondingly high for such a number of pipets, and so are the requirements of positional accuracy. In practice the gel can only be oriented vertically because otherwise the sample wells might leak.
A procedure of the initially cited kind is known from the patent document WO 94/11529. The sample substance is chemically specifically bonded to the teeth of the comb-shaped sample feeder. After the sample feeder has been moved to the electrophoresis gel, the specific chemical bond is dissolved by adding an appropriate means (formamide), whereby the sample substance then is able to detach from the sample feeder and able to penetrate the gel under the action of the electric field. The comb-shaped feeder only comprises 8 teeth and accordingly only eight samples can be analyzed simultaneously. This feature may be due to the fact that only comparatively wide teeth allow providing sufficient sample substance.
The objective of the invention is to create a method of the cited kind to allow effective and simple sample transport.
This problem is solved in that the sample feeder comprises at least one porous material element of such pore size that the sample substance is kept in the liquid state by capillary forces in the said porous material at least when the sample is picked up by the sample feeder and when the sample is delivered to the sample processor. Accordingly the sample substance is kept in the liquid state merely by capillary forces during sample pickup or sample delivery. In the interim, the sample substance is present, though not mandatorily, in dried form in the pores of the porous material. In any event complex mechanisms such as multi-pipeting systems are eliminated. As regards sample delivery, the porous material need only be brought into contact with the sample substance in the liquid state; no reactions to chemically bond the sample substance to the sample feeder are at all required, nor are the chemical reactions during sample delivery to dissolve the chemical bond between sample substance and sample feeder. Because the capillary forces keep the sample substance in the liquid state during sample transport until transfer into the sample processor, and this regardless of the direction of gravity, restrictions no longer are incurred on the orientation of the sample processor. The porous material may be laminar and thus may be inserted in problem-free manner between the glass plates of a gel electrophoresis apparatus. At least the material part of the sample feeder consists preferably entirely of a porous material, as a result of which the capacity of the material element for the sample substance shall be relatively high. Therefore it is enough to use small-format material elements to allow a corresponding plurality of compactly configured material elements. For a given width of the electrophoretic gel, the number of the samples which must be analyzed simultaneously can therefore be significantly raised, for instance to 192, even 384 samples.
In a further development of the invention, following sample pickup by the feeder, the sample is dried and the feeder is moved into a liquid phase before the sample is delivered. The sample feeder dried in the interim is especially easily manipulated; the danger of interim contamination is substantially reduced.
To constrain the sample feeder to deliver the sample to the sample processor, the sample feeder can be processed, for instance mechanically, illustratively being mechanically compressed, or compressed air being blown through it. However, in especially preferred manner, an electrical field is generated in the zone of the sample delivery site to cross the material element in order to generate a current of electrically charged molecules, macromolecules or particles of the sample substance from the porous material element into the sample processor. The electric field intensity is selected in such manner as a function of electric charge that the capillary forces are overcome. The use of this method stage is especially advantageous in electrophoresis because it including anyway means for electric field generation.
The sample feeder loaded with the sample substance being especially easily manipulated as indicated above, there follows the advantageous option to move the sample feeder, once loaded with sample, from the sample pickup site to the sample delivery site. Thus the sample can be picked up at a site arbitrarily away from the sample processor apparatus.
Alternatively however the sample also may be moved from the sample pickup site to the sample delivery site in that, provided there be physical connection implemented by the porous material element of the sample pickup site between the sample pickup and delivery sites, the capillary forces shall ensure sample transport. This kind of sample feeding process is used foremost when the sample delivery site is unduly inaccessible or highly compact, for instance as regards microchip sensors, in particular DNA sensors. In such cases a separate material element, independent of the others' material elements, is used for each sample, so as to avoid cross-talk, that is mixing of sample substance, from the beginning, an event which otherwise, in the light of the comparatively large quantities of sample substance involved, might occur.
However the feasibility of mixing also may be exploited in controlled manner in that the porous material will be wetted at different sites or consecutively at the same site with the substances to be mixed. Illustratively, by appropriate additions, proteins (for instance antigens) may be mixed in the porous material with antibodies, or DNA with complementary hybridization DNA or DNA with labeling means.
Comparatively small amounts of sample substance may be used in the first above alternative of physical transport of the sample feeder from the sample pickup site to the sample delivery site, and consequently the danger of crosstalk in general can be disregarded also where connected material elements are involved.
Because of the above easy handling and the comparatively high capacity for sample substance of the porous material element, a preferred feasibility is offered, namely a sample processor comprising a plurality of sample delivery sites operates with a corresponding plurality of porous material elements.
As already mentioned, separate material elements may be used each time, the method comprising rigorous separation without danger of crosstalk. However the manufacture and handling of the material elements will be substantially simplified if the sample feeder of the invention comprises one material element support bearing the material elements in an array corresponding to the configuration of the sample pickup sites. The sample feeder in this design may be substantially like a comb when the sample pickup sites are confined in linear or arcuate manner.
The sample feeder can be manufactured in especially simple manner, for instance by stamping, if it includes a sheet of porous material comprising all p

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