Sensors

Details Sensors Sensors

1998-06-30

2001-06-12

Soderquist, Arlen (Department: 1743)

Chemistry: analytical and immunological testing

Metal or metal containing

Li, na, k, rb, cs, fr, be, mg, ca, sr, ba, ra

C422S051000, C422S067000, C422S082050, C422S082060, C422S082070, C422S082080, C436S073000, C436S074000, C436S172000

Reexamination Certificate

active

06245574

ABSTRACT:

The present invention relates to sensors with valinomycin derivatives for the optical determination by fluorescence of K
+
ions in aqueous systems, whereby the valinomycin derivatives contain a fluorescence dye which emits in long waves and is covalently bound by a bridging group; coating masses with these valinomycin derivatives; these valinomycin derivatives; an optical process for the qualitative and quantitative determination by fluorescence of K
+
ions in aqueous systems, and the use of the sensors for the optical determination by fluorescence of K
+
ions in aqueous systems.
The use of valinomycin as a highly specific ionophore for the determination of K
+
ions in aqueous systems, e.g. in blood, has been known for a long time. Natural valinomycin is a cyclodepsipeptide, which is made up of the elements D-valine (D-Val), L-lactic acid (L-Lac), L-valine (L-Val) and D-&agr;-hydroxyisovalerianic acid (D-Hyisval), whereby said elements in the sequence indicated form a part sequence which is repeated three times in the 36-membered macro ring of valinomycin. The structure of natural valinomycin may also be described in abbreviated written form by the formula
cyclo-(D-Val-L-Lac-L-Val-D-Hyisval)
3
.
The macro ring of valinomycin forms a hollow cylinder in which K
+
ions are embedded. As a result of the change in charge thus induced, a discernible change is brought about in an indicator molecule, for example a fluorescence dye, which is present simultaneously, and this change can be referred to for the qualitative and quantitative determination of K
+
ions.
Conventional systems, which contain valinomycin as an ionophore, are multi-component systems which consist essentially of a polymer membrane which contains valinomycin as an ionophore, a fluorescence dye as an indicator molecule, and a lipophilic salt. The disadvantages of these systems is their poor stability and too long response time. Here, the poor stability is caused in the first instance by washing out of the active components, and the long response time is caused by the comparatively large physical distance between the ionophore and the fluorescence dye.
It has been found that the high specficity of valinomycin is maintained if a fluorescence dye as the indicator molecule is covalently bound by a bridging group to the macro ring of the valinomycin. It was also found that stable sensor systems with rapid response time are obtained if those valinomycins that are modified by covalent binding with a fluorescence dye are dispersed in a polymer membrane which is found, in such a case, as a layer on an appropriate carrier.
An object of the present invention is sensors for the qualitative and quantitative determination of K
+
ions in aqueous systems, which consist essentially of a carrier and an active layer applied to this carrier. The sensors according to the invention are characterised in that the active layer contains a polymer in which at least one modified valinomycin of formula I is dispersed,
in which one of radicals R
1
to R
12
signifies a group of formula a,
in which R
a
signifies hydrogen or methyl, m and n, independently of one another, denote 0 to 6, whereby in the alkylene group —(C
n
H
2n
)— for n>0, a methylene group can be replaced by a phenylene or cycloalkylene radical, L is a bridging member formed by the reaction of two functional groups which are capable of reacting together, and A signifies the radical of a fluorescence dye emitting in long waves with an emission wave length of >550 nm, and the remaining radicals R
1
to R
12
, independently of one another, signify methyl or isopropyl.
The compounds of formula I, in which the ionophore is covalently bound to a fluorescence dye by a bridging member are called fluoroionophores.
The carrier materials employed for the sensors according to the invention are opaque, translucent or preferably transparent materials. Suitable carrier materials are synthetic materials such as polycarbonates or acrylic glass, or mineral materials, metal oxides or mineral glass. Preferred carrier materials are organic or mineral glass. The carrier may be of any shape. Preferred shapes are for example sheets, cylinders, tubes, channels, ribbons or fibres.
Suitable polymers into which the fluoroionophores of formula I may be incorporated are those which enable a transparent or slightly opaque coating to be produced on the carrier. The polymers that may be considered are in particular acrylic polymers, such as poly-N,N-dimethyl acrylamide, polyethyl acrylate, polyethyl methacrylate, polyethylhexyl acrylate and acrylic polymers. Further suitable polymers are polyvinyl chloride, polyvinyl acetate, polyethylene, polypropylene and polyester, such as polyethylene terephthalate and polystyrene.
The thickness of the layer to be applied to the carrier may be from 0.01 to 100 &mgr;m, preferably 0.1 to 50 &mgr;m, especially 0.1 to 30 &mgr;m, most preferably 0.1 to 10 &mgr;m. The layer which is applied to the carrier may be transparent or slightly opaque. The layer is preferably transparent. Hydrophilic layers are also preferred.
Preparation of such layers may take place in a manner known per se, for example by dissolving a compound of formula I and a suitable polymer in a solvent, then applying the solution to the carrier and removing the solvent. The solution may be applied by pouring, or by employing processes which are known from lacquering technology. Such processes which may be named are in particular brushing, spin coating, spraying and screening processes. The layers are preferably applied by the spin coating process.
The solvents which may be considered are water, alcohols, ethers, esters, acid amides, halogenated hydrocarbons and ketones. Examples of such solvents are methanol, ethanol, n-propanol, isopropanol, diethyl ether, methyl isobutyl ether, tetrahydrofuran, dioxane, ethyl acetate, butyl acetate, dimethylformamide, dimethyl acetamide, methylene chloride, chloroform, acetone, methyl ethyl ketone and methyl isobutyl ketone. It is preferable to use readily volatile solvents, especially tetrahydrofuran, methylene chloride and acetone. One especially preferred solvent is tetrahydrofuran. The above-mentioned solvents may be used alone or as solvent mixtures. A viscosity of the coating compositions according to the invention which is appropriate for coating may be set by using an appropriate amount of the solvent respectively used.
A further object of the present invention is coating agents which contain a suitable polymer and a compound of formula I. According to one embodiment, these coating compositions may exist in the form of a powder which contains an appropriate polymer, a compound of formula I and optionally further additives in finely dispersed form. Suitable additives are for example lipophilic salts and softeners. According to another embodiment, the coating agents may exist in the form of solutions, such as those obtained by dissolving the above-mentioned powder mixtures in one of the above-mentioned solvents.
The groups L, which are formed by reacting two groups that can be reacted with one another, may be the following: —O—CO—; —CO—O—; —S—CO—; —CO—S—; —NR
13
—CO—; —CO—NR
13
; —NR
13
—SO
2
—; —SO
2
—NR
13
—; —O—CO—NR
13
—; —NR
13
—CO—O—; —S—CO—NR
13
—; —NR
13
CO—S—; —N(R
13
)—; —NH—CO—NH—, —NH—CS—NH— and —O—, whereby R
13
signifies H or C
1
-C
4
-alkyl. Preferred groups L are the ester groups, the carbonamide groups, the sulphonamide groups and the urea group. An especially preferred group is the carbonamide groups.
The suitable fluorescence dyes in question, which emit in long waves, are generally polycondensated aromatics from the group of acridines, benzopyrans and dibenzopyrans, which contain reactive groups that are suitable for binding with the modified valinomycins according to the invention. Such groups are for example —COOH, acid halides, such as —COHal and —SO
2
Hal, whereby Hal signifies chlorine or bromine in particular, ester groups such as —CO—O-alkyl, —CO—O-aryl, —SO
2
—O-alkyl and —SO
2
—O-aryl, and groups

Affiliated with

Also associated with

Rating

Sensors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Sensors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sensors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2516809