Chemistry: electrical and wave energy – Apparatus – Electrophoretic or electro-osmotic apparatus
Reexamination Certificate
2000-03-21
2002-12-17
Warden, Jill (Department: 1743)
Chemistry: electrical and wave energy
Apparatus
Electrophoretic or electro-osmotic apparatus
C204S643000, C204S666000
Reexamination Certificate
active
06495016
ABSTRACT:
The invention relates to general measuring systems in the sector of analytical laboratory technology, in which microfluidic microchips are used for the chemical, physical, and/or biological analysis or synthesis of substances, which feature a channel structure by means of which the substances, with the imposition of a physical potential, and of an electrical or hydraulic potential in particular, are capable of movement in accordance with the channel structure. The invention relates in this context, in particular, to the injection of substances into such a microfluidic microchip.
A microchip of the type described in the preamble, and a corresponding microchip laboratory system, are described, for example, in U.S. Pat. No. 5,858,195. In a microchip of this kind, the substances concerned are moved by means of a system of channels connected to one another and integrated on the microchip. The movement of these substances in these channels is controlled by means of electrical fields, which are imposed along these transport channels. Because of the high-precision control of the substance movement which this makes possible, and the very exact metering capacity of the substance masses moved in each case, the substances can be mixed precisely with regard to the stoichiometry required, can be divided, and/or can induce chemical or physical-chemical reactions. With this microchip, the channels provided for in the integrated structural design feature a plurality of substance reservoirs, which contain the substances required for the chemical analysis or synthesis. The movement of the substances from these reservoirs along the transport channels is effected in this case by electrical potential differences. The substances moving along the transport channels accordingly come in contact with different chemical or physical environments, which then make possible the required chemical or chemical-physical reactions between the individual substances. In particular, the microchip features one or more crossings between the transport channels, in which the intermixing of the substances takes place. By the simultaneous use of different electrical potentials on the different substance reservoirs, it becomes possible for the volume flows of the different substances to be selectively controllable by means of one or more crossing points, and therefore, solely on the basis of the electrical potentials applied, for a precise stoichiormetric yield to be effected.
The movement of the substances by means of electrical high voltage in this situation, however, represents only one variation. For example, it is possible for the potential difference required for the movement of the substances also to be implemented by means of imposing a pressure means on the substances, for preference a suitable gas means such as a noble gas. The movement of the substances can also be effected by the use of a suitable temperature profile, in which situation the movement takes place due to the thermal expansion of the particular substance. The selection of the individual means for the provision of a potential or of a force for the movement of the substances on the microchip is based in this case in particular on the physical properties inherent in the individual substances. In the case of substances with charged particles, such as charged or ionized molecules or ions, the movement of the substances is effected for preference by means of an electrical or electromagnetic field of suitable strength. The path which the substances pass over in each case is calculated in this situation in particular on the basis of the field strength and the duration of the field applied. The movement of the substances is effected in this case either etectrokinetically, in other words, in the case of charged substances, due to the effect of the external electrical field on the charge which is present in each case. As an altemative, or in parallel with this, the movement of the substance can be effected by electro-osmosis in the case of substances (particles) in solution in solvents, in which situation the solvent is essentially moved on the basis of a charged double layer being formed with many materials, such as glass, on the surface which is adjacent to an electrolyte, and accordingly incurring a net counter-current of the substances. In the case of substances which are free of an electrical charge, however, or which are not in solution, the movement of the substances is effected in most cases with the aid of what is referred to as a flow means.
The microfluidic microchips described are therefore particularly characterised by the fact that, because of the very small dimensions of the transport channels on the microchip, only relatively small volumes of substance are moved, in the range from picolitres to nanolitres. An analysis or synthesis of small substance volumes of this type therefore also implies extremely high-resolution detection devices for the measurement of these small substance masses. The measurement resolution of such measuring devices is therefore largely determined by the sensitivity of the detector used in each case, as well as the underground noise caused by the measurement arrangement as a whole.
It is known that the signal-to-noise ratio of the measuring devices concerned in this case can in principle be substantially improved by the tests which are to be conducted in each case being carried out several times, and by mean values then being formed from the measuring results obtained. With this procedure, however, it must be borne in mind that certain tolerances are to be maintained between the repeated measurement cycles, in order in particular to avoid the mixing of substances or the superimposition of the measurement signals detected. These dead periods and the pulse widths in each case for the injection of substances therefore also determine, conversely, the minimum duration of a measuring cycle, and therefore also directly determine the limits of the signal-to-noise ratios which can in principle be achieved.
In addition to this, the measurement cycle can also in principle be shortened by multiple substance injection during an analysis attempt, in particular when substance separation is being carried out. This has the disadvantage, however, that the measurement signals which are superimposed in this process must subsequently be relatively laboriously disentangled. It is often also not possible to carry out subsequent disentanglement of the measurement signals with sufficient precision.
The object underlying the invention is to provide a microfluidic microchip of the type concerned, as well as a process for its operation, with which, despite the physical and technical restrictions described heretofore, the signal-to-noise ratio can be improved in comparison with the pertinent prior art during the performance of the tests described.
A further object involves achieving such improvement withoutstantial volumes of the substance to be processed being required, or additional costs being required for the manufacture of such microchips.
These objectives are achieved according to the invention by the features of the independent claims. Preferred and advantageous embodiments of the invention are described in the dependent claims.
According to a first variant of the microchip according to the invention, provision is made in particular for the fact that, in a first operating cycle or a first operating phase, a leading channel or leading channel section can be filled with a continuous substance flow by the imposition of a constant potential on a feed channel and a discharge channel, whereby the individual substance components, in particular the slowest moving substance components, extend continuously and homogenously along the leading channel. Once a continuous volume flow of substance of this kind has been formed, the substance volume contained in the leading channel can to advantage be guided out of the leading channel by switching over the potential, and can be injected into a channel provided for the conduct of the test.
By means of this ty
Agilent Technologie,s Inc.
Brown Jennine
Warden Jill
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