Fluent material handling – with receiver or receiver coacting mea – Diverse fluid containing pressure filling systems involving... – Filling with exhausting the receiver
Reexamination Certificate
2001-04-26
2002-12-31
Douglas, Steven O. (Department: 3751)
Fluent material handling, with receiver or receiver coacting mea
Diverse fluid containing pressure filling systems involving...
Filling with exhausting the receiver
C141S192000, C141S301000, C222S282000, C222S422000
Reexamination Certificate
active
06499515
ABSTRACT:
This invention relates to a gas cushion proportioning microsystem to proportion extremely small liquid volumes in the microliter and sub-microliter ranges.
In the known proportioning systems, a rough distinction is made between pipettes, dispensers, and multi-functional proportioners. Pipettes will redischarge the liquid volume received in one step. In dispensers, the discharge of the liquid volume received is performed stepwise. Multi-functional proportioners allow for both modes of operation. All of the system types also exist in a multi-channel design and permit to simultaneously perform several identical proportioning operations.
Conventional reciprocating-piston pipettes are designed as fixed-volume or adjustable-volume pipettes and operate in a volume range from somewhat less than 1 &mgr;l up to about 10 ml. A piston is displaced in a cylinder, which moves a gas cushion in order to draw a liquid specimen into a pipette tip or to eject it therefrom. This has the advantage that the liquid does not come into contact with the reciprocating-piston pipette, but only contaminates the pipette tip. Therefore, this one mostly is designed as an expendable article (a “disposable”), particularly in plastic, and will be exchanged against a clean pipette tip after use.
Proportioning by means of reciprocating-piston pipettes is burdened with various system-related errors. In adjustable-volume reciprocating-piston pipettes, a pipetting error arises by the fact that the weight of the liquid column “is suspended” from the gas cushion and stretches it differently depending on the liquid volume adjusted. It is particularly for minor volumes being proportioned that proportioning accuracy is significantly affected because the pipette tip is wetted by the liquid being proportioned. Moreover, reciprocating-piston pipettes are incapable or only of a restricted capability of using open jets for small volumes being proportioned. No complete liquid discharge in an open-jet is reached already if the volumes being proportioned are of a few microliters and less. In addition, it is just for small volumes being proportioned that the reception of liquid considerably depends on the depth of immersion of the pipette tip into the liquid and the alignment of the reciprocating-piston pipette. This can be a significant source of errors especially in hand-operated pipettes. As a result, conventional reciprocating-piston pipettes are able to pipette small volumes only to a limited extent and at a relatively high imprecision and incorrectness.
Conventionally designed proportioning systems operating according to the direct-displacement principle include tips referred to as “syringes” with an integrated piston which is coupled to a driving device of the proportioning system. They are employed in a volume range from about 1 &mgr;l to 50 &mgr;l. Since there is no gas cushion and the piston is in a direct contact with the specimen being pipetted direct displacers are employed particularly if liquid of high vapour pressures, high viscosities or high densities is proportioned. This system type avoids the error resulting from the varying stretch of the gas cushion. However, proportioning small volumes at the accuracy required will be possible at best down to about 1 &mgr;l. Also, direct-displacement syringes which can proportion such liquid volumes in an open jet are relatively expensive.
From WO 99/10099, a proportioning microsystem is known which comprises a reservoir, a membrane micropump the inlet of which is joined to the reservoir, an open-jet proportioner the inlet of which is joined to the exit of the membrane micropump, a proportioning port joined to the exit of the open-jet proportioner, and a proportioning control disposed in an operative communication with the membrane micropump and the open-jet proportioner. The membrane micropump is capable of pumping liquid into the open-jet proportioner from the reservoir. The open-jet proportioner is capable of dispensing the pumped-in liquid in an open jet. The open-jet capability makes it possible to proportion volumes being proportioned without no carry-over in the range of 1 nl up to a few microliters at high proportioning accuracies. If proportioning is to be made with another liquid this direct-displacement proportioning microsystem either needs to be cleaned to avoid carry-overs or to needs to be exchanged against a clean proportioning microsystem.
The same document has made known a microproportioning apparatus which has a membrane micropump which displaces a column of auxiliary liquid which, by means of a pipette piston, draws liquid into a pipette tip through a proportioning port or ejects it therefrom. The desired volume being proportioned is reached via the control of the known stroke volume of the membrane micropump. After a proportioning operation, the pipette tip and some of the column of auxiliary liquid may be discarded. In this system, the liquid flows off through the proportioning port and may be deposited on a substrate. It is impossible to deliver liquid in an open jet. Errors may occur particularly owing to wetting effects and, further, by differing depths of immersion and alignments. Therefore, its usability for proportioning extremely small liquid volumes is limited. In addition, there is a risk of contaminations because the pipette tip and the substrate contact each other.
Accordingly, it is the object of the invention to create a proportioning microsystem to proportion extremely small volumes in the microliter and sub-microliter ranges at an increased accuracy and a reduced risk of contamination and carry-over.
The object is attained by a gas cushion proportioning microsystem according to claim 1. Advantageous aspects of the system are indicated in the sub-claims.
The inventive gas cushion proportioning microsystem to proportion liquid volumes in the microliter and sub-microliter ranges comprises
1.1 a liquid reservoir including a storage space for the liquid being proportioned the boundary line of which is broken through by an outwardly leading liquid passage and a gas passage.
1.2 a gas displacement system which has a micropump to pump a gas, and a connection to the gas passage, and
1.3 a proportioning control disposed in an operative communication with the micropump to generate a negative pressure or positive pressure by actuating the micropump, and to apply the negative pressure or positive pressure to the liquid reservoir in order to receive liquid in the storage space through the liquid passage or to deliver it from said space.
A proportioning microsystem in the sense of the present application is a proportioning system which serves for proportioning small liquid volumes in the microliter range and sub-microliter range (from abt. 50 &mgr;l to abt. 1 nanoliter). What is characteristic of such proportioning microsystem is micropumps which are designed in the microsystem technology. Their manufacture in the microsystem technology specifically comprises the use of the following materials: semiconductors and/or plastic and/or glass and/or ceramics and/or metals. Those are processed by means of appropriate manufacturing techniques of the microsystem technology or by microstructuring them, e.g. by lithography and etching processes (for semiconductors) or LIGA processes (for metals, plastics, and ceramics).
The micropump concerned may specifically be a membrane micropump. A membrane micropump in the sense of the present application is a pump with a cavity which is defined by at least one membrane with which an actuator (a drive) is associated. The actuator may specifically be a piezoelectric actuator. However, other actuators may be employed as well, e.g. thermal-action actuators. A membrane micropump may be with no valve so as to act as a displacement device to displace a volume during a stroke. However, it may be equipped with valves which are switched in such a way that several successive strokes of the membrane produce a volume flow. Passive-response valves, which are controlled by the pressures applied, generally allow of a unidirectional oper
Douglas Steven O.
Eppendorf AG
Sidley Austin Brown & Wood LLP
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