Membrane for chemical and biosensors

Details Membrane for chemical and biosensors Membrane for chemical and biosensors

1998-10-29

2004-03-16

Alexander, Lyle A. (Department: 1743)

Chemistry: analytical and immunological testing

Measurement of electrical or magnetic property or thermal...

C436S166000, C436S169000, C422S067000, C204S400000, C204S402000, C204S403050

Reexamination Certificate

active

06706532

ABSTRACT:

The present invention relates to a membrane which is intended particularly, but not exclusively, for use in a sensor, to a sensor incorporating such a membrane, and to a detection method utilising the membrane. The membranes of the invention are intended most particularly (but again not exclusively) for use in chemical and biosensors, e.g. for determining the amount of lactate in whole blood, (this being a measure of the oxygenated state of tissue).
BACKGROUND OF THE INVENTION
Biosensors are used for detecting the presence and/or amount of a selected component in a sample, e.g. blood. It is well known that biosensors comprise a combined detection arrangement of a biolayer such as an enzyme and a transducer. Certain types of biosensors have a membrane structure which comprises one or more membranes and which (in use of the biosensor) separates the detection arrangement from the sample being analysed. The membrane structure may contain a biological component (e.g. an enzyme) but usually separates the biological component from the sample. In the case of an enzyme there is a reaction with the species of interest to produce a product which is detected by the transducer; this gives one type of arrangement for “indirect” determination of the species of interest.
The membrane structure of the biosensor will generally include an outer membrane of a synthetic polymeric material which has been modified to produce a membrane which is permeable to the species of interest (or more permeable than a similar membrane produced from polymeric material which has not been modified). If the biosensor is to be used for operation in whole blood then the outer membrane (of the membrane structure) which comes into contact with the blood has to meet high demands on biocompatibility since sample pre-treatment preferably does not take place. The membrane surface will be a target for plasma proteins which will begin to adsorb rapidly after the initial contact with blood. Initial protein adsorption will be followed by complement activation, adhesion of cells and cell components and fibrin clot formation.
Operation in whole blood also puts demands on the linear range of the sensor which has to be much wider when there is no dilution of the sample prior to analysis.
DESCRIPTION OF THE INVENTION
According to a first aspect of the present invention there is provided a membrane comprised of a synthetic polymeric material incorporating a surface active agent.
By “surface active agent” we also mean “surfactants” and the terms may be used interchangeably.
The invention has been based on our finding that the incorporation of a surface active agent in a synthetic polymeric material renders membranes, produced from that material permeable (or more permeable) by mass transport to a species of interest whilst providing membranes which have good blood compatibility and which may be used to provide a response—linearising diffusion barrier. This is particularly the case for enzymes which have a reaction with the species of interest which has a rate that is not linear with respect to substrate concentrations when these are high (typically well above the enzyme Michaeli's constant).
The membranes may be rendered permeable to uncharged species or to charged species and may therefore be used in biosensors for determining the presence and/or amount of such charged species, e.g. the concentration of lactate present in a sample.
Membranes in accordance with the invention have the significant advantage of being blood compatible and may therefore be used in chemical sensors and biosensors for determining the amount of a species in whole blood. The membranes are thus particularly suitable for use in biosensors for determining the amount of lactate in whole blood. The membranes of the invention may however be used for other purposes, e.g. dialysis and as permeable covering layers on other enzyme and even non-enzyme electrodes. Moreover the membranes have utility in sensors for determining uncharged species, e.g. glucose and in chemical sensors which have no biological component.
It is a further advantage of the membranes of the invention that they provide a linearising diffusion barrier for the species of interest, i.e. the amount of the species present in a sample which is able to diffuse across the barrier is proportional to the amount of that species in the sample, but the concentration achieved after the barrier is crossed is thereby lowered and within the range for which the chemical or biosensor has a linear signal output.
Preferably the synthetic polymeric material is poly(vinylchloride). Preferably the poly(vinylchloride) will have a molecular weight (Mw) in the range 80,000 to 250,000, more preferably 150,000 to 250,000, e.g. about 200,000.
The amount of the surface active agent present in the membrane is generally at least 1% by weight of the synthetic polymer, e.g. more preferably at least 2%, even more preferably at least 3% on the same basis. Generally the amount of surface active agent is less than 250% by weight of the synthetic polymer. If the membrane is to be used in a sensor as a linearising diffusion barrier then the amount of surface active agent will depend on the intended use of the sensor. For some applications (e.g. use of the sensor under continuous flow conditions) it may be desirable for the amount of surface active agent to be at least 50% by weight of the synthetic polymer. For other applications the amount of surface active agent may be less than 50% (w/w) of the synthetic polymer, e.g. less than 30% or even less than 20% on the same basis. For dialysis membrane function, high mass transport (permeability) is required and higher amounts of surface active agent are demanded, typically in the range 100% to 200% (more preferably 150% to 200%) (w/w) of the synthetic polymer.
The surface active agent is preferably a non-ionic surface active agent. Such non-ionic surface active agents are particularly useful for avoiding specific ionic interactions with diffusing solute. Alternatively the surface active agent may be a cationic or anionic surfactant.
A variety of non-ionic surface active agents may be used. Surface active agents which are useful in the present invention include compounds comprised of or incorporating polyoxyalkylene residues. The alkylene oxide may for example be ethylene oxide and/or propylene oxide. Examples of such surface active agents include compounds of the formula (I)
Typically the molecular weight of compound (I) will be in the range 500 to 800, e.g. from 600 to 700. A particularly suitable product of the formula (I) has a molecular weight of about 648 and is available under the name Triton X-100.
Further examples of surface active agents comprising poly(alkylene oxide) residues are block copolymers of ethylene oxide and propylene oxide. Suitable examples of such copolymers for use as surfactants have a molecular weight of 5000 to 10000, more preferably 7000 to 10000.
The block copolymer may be of the following general formula (I).
The block copolymer of ethylene oxide and propylene oxide may for preference have an ethylene oxide content of at least 75%, preferably about 80%, by weight of the surfactant.
Examples of preferred surfactants comprised of block copolymers of ethylene oxide and propylene oxide are available under the name PLURONIC. A particularly suitable example of such a product is available under the name Pluronic F-68 and has a molecular weight of about 8400.
If the surface active agent comprises a block copolymer of ethylene oxide and propylene oxide then it (i.e. the surface active agent) may comprise, for example, 4.5 to 100% by weight of the synthetic polymeric material, e.g. 6% to 100%, more preferably 10% to 90%, even more preferably 40% to 70%, and even more preferably 50% to 60% by weight on the same basis.
A further surface active agent which may be used is L-&agr;-phosphatidyl choline dipalmitoyl (C
40
H
80
NO
8
P) (M
w
=734). This surface active agent occurs naturally as a pulmonary surfactant and has advantages from the point of view of biocom

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