FR2768632A1 - Self-sampling and assay device - Google Patents

Abstract

Device that allows individuals to take and assay samples of their own body fluids comprises a syringe, which can be a piston-type syringe or a "micro-reservoir needle" a needle attached to a flexible bulb, containing membranes or filters and reagents (enzymes, coenzymes and buffers) and chromogenic indicators for assaying analytes in the samples.

Description

The present invention relates to modifications made to current devices for withdrawing and injecting biological or medicinal liquids, which modifications allow them to detect and measure parameters, extemporaneously.

One of the frequent jobs will be monitoring sugar levels in diabetics or screening for diabetes in underdeveloped countries or in communities in other countries.

State of the art:
Currently, medical devices, equipped with a needle, for treatment at the patient's home: - Allow, for some the collection and collection of biological fluid, without authorizing the collection and injection of medication.

- Allow for others, thanks to a piston or a deformable reservoir, the collection and injection of biological fluid and medication.

- Cause, for still others, the flow of biological liquid without being able to take samples, it is the lancing device.

A) Medical sampling device. Fig. 1.

It includes a needle (Aig) of 80-90 / 100 Zm in diameter mounted on a plug (Bouc) of flexible and compact polymer (PS), obstructing a rigid and transparent polymer tube (PR) or glass, of 10- 20 cm3 of volume.

It has no piston.

It allows the removal of biological fluid, by puncturing a vein or artery, thanks to the tightness of the stopper maintaining the vacuum in the tube.

It does not allow injection of medication.

B) Disposable medical devices, biological fluid collection and drug injection in humans or animals:
There are two devices: 1) The rigid polymer syringe, with plunger and needle.

2) The micro-reservoir needle or AMR. It is a needle surmounted by a small flexible and deformable polymer reservoir without piston, we have already patented it.

1) The syringe. Fig. 2.

It is made of a syringe body (C) and a piston (P) made of rigid polymer (PR). The piston is reinforced by an elastomer disc (EL)
DESCRIPTION:
The syringe body (C):
It is cylindrical, graduated, from 1 to 20ml in volume, made of rigid polymer (PR) and translucent.

The internal wall is lubricated with a silicone oil.

One of the tapered ends allows the needle base (EM) to adapt.

The other end, of larger diameter, allows the introduction, the grip and the play of the piston (P) and (M).

A piston (P):
One end, lined with an elastomer pad (EL), seals and plays in the body of the syringe, the other end (M) is handled by the operator for suction and return of the sample.

The needle (Aig):
Its attachment to the piston body is mobile. Its diameter is 80 / 100mm, its bevel is adapted to the desired sample either from the vein or artery or the cerebrospinal fluid.

The sample is never taken from the finger pulp.

OPERATION:
The syringe with its needle is used in medicine or outside medicine.

The manipulator pulls on the piston (P) using the handle (M) to withdraw the biological liquid or the injectable medication by aspiration; It pushes the piston (P) to expel the liquid <L) through the needle (Aig).

Their stay in the body of the syringe is limited by the possibility of migration of polymer components in the liquid to be injected. The piston can be completely withdrawn through the opening (O).

USE:
In medicine, the syringe allows the withdrawal by aspiration of any biological fluid: venous, arterial, cerebrospinal fluid.

BECOME A LEVY:
The syringe body is used for collecting, rarely for depositing the biological fluids collected, it does not allow extemporaneous analysis of the collected sample.

Biological fluids, blood and cerebrospinal fluid, collected and collected in the body of the syringe are placed in vials for transfer to an analysis laboratory.

The syringe also allows the withdrawal of medication.

These, collected by aspiration into the body of the syringe, are injected into the human body by all reliable injection routes with adequate adaptation of the dimensions of the needle in particular.

B) The micro-reservoir needle or AMR. Fig. 3.

It includes a needle (Aig) surmounted by a flexible polymer (PS) reservoir (R).

DESCRIPTION
The tank is made of flexible polymer (PS), translucent or even transparent and deformable, without piston.

It contains 100 ssl, 100 microliters.

The irremovable needle (Aig) attached to the polymer is ultra-fine, 30 / 100mm in diameter of the type used in acupuncture.

Notes: In the initial patent on the AMR that I filed, patent no. 88 10774, I specified the sizes of the reservoir, the volume of the reservoir, as well as the diameters of the needle.

The modifications that we are making today in the injection devices at the level, in particular of the AMR reservoir or of the body of the plunger syringe or of the needle, are patented whatever the dimensional coordinates of the different components of injection devices.

OPERATION:
It allows the restitution of approximately 100 microliters previously aspirated by releasing the bidigital pressure on the reservoir.

USE:
AMR does not allow sampling or injection into a vascular axis.

It allows the aspiration of biological fluid: for example, sampling of 2-3 drops of blood from the finger pulp or elsewhere under the skin then restitution, the EM base serving for gripping the AMR.

It allows the suction of 100 microliters of medicated liquid for its immediate re-injection into the skin.

BECOME A LEVY:
The 2-3 drops of blood returned are brought into contact with a colorimetric strip as with the lancing device,
The 100 micro liters of medication previously aspirated are re-injected under the skin.

C) Other device.

The lancing device. Fig. 4:
DESCRIPTION:
The size of an ink tank pen, it covers
the handle (MA) a button (End). At the other end, a
small structure (Stru), interchangeable, in rigid polymer
finished with a needle, (Aig).

OPERATION:
The localized pressure on the button activates a small spring and allows the small blade to pierce the skin of the finger pulp to let one or 2 drops of blood flow.

There is no suction, the blood flows outside, the device does not allow its collection.

USE:
The drop of blood, taken and obtained by slight piercing of the finger pulp, is brought into contact with colorimetric strips.

BECOME A LEVY:
The strip after the enzymatic reaction turns color. The colorimetric shift allows its reading.

The assay is done by reflectometric reading of the strip.

Reflectometry also makes it possible to determine many biological parameters in living beings.

In conclusion,
The devices we have make it possible to collect biological fluids and blood in particular, but they cannot analyze or cannot self-analyze any of the parameters of the collected liquids.

The lancing device allows diabetics to deposit a drop of blood from the finger pulp on a colorimetric strip and to measure a parameter.

THIS INVENTION CONCERNS THE MODIFICATIONS MADE TO:
EXISTING MEDICAL DEVICES FOR INJECTION: PISTON SYRINGES AND
AMR.

THESE MODIFICATIONS ARE MADE TO THE SYRINGE BODY OF THE PISTON SYRINGE,
TO THE PISTON OF THE SYRINGE AND TO THE TANK OF THE AMR Whatever the size of
THEIR RESPECTIVE COMPONENTS (SYRINGE BODY, NEEDLE, PISTON, TANK
AMR).

THESE MODIFICATIONS ALLOW FOR EXTEMPORARY DETECTION OF PARAMETERS
ORGANIC ORIGIN IN LIVING BEING OR PARAMETERS OF MINERAL ORIGIN,
THANKS TO REACTIONS OCCURRING WITHIN THE SYRINGE BODY OF THE
PISTON SYRINGE OR ANR TANK OR IN THEIR WALL.

THESE MODIFICATIONS ALLOW FOR EXEMPTIONAL DOSAGE OF THESE PARAMERERS, A
THE INSIDE OF THE SYRINGE BODY OF THE PISTON SYRINGE OR OF THE TANK
AMR.

The modifications of the sampling-injection tool, object of this patent, therefore include, the assay technique, and obtaining the result of the assay of the blood parameter sampled.

Thus the drops of blood taken from the finger pulp or elsewhere will allow the determination of parameters determined thanks to the modifications made.

THE MODIFICATIONS, subject of this patent, Fig. 5, relate to the plunger syringe or the AMR and allow:
highlighting the parameter that it is blood,
urinary, humoral, of human or animal origin,
inside the AMR reservoir or syringe body
piston.

The dosage of the blood parameter inside the reservoir
AMR or plunger syringe body.

These modifications are:
The contribution of test elements.

Structural changes in the syringe polymer or
AMR in its molecular texture or on its internal surface.

The adaptation of the syringe body light and
AMR by providing filters and membranes.

A. Test items.

These are enzymes (Enz), coenzymes (Coenz) and buffers (Tamp), reacting with the parameter to be assayed. The reaction developed between the parameter to be assayed and the coenzyme, the enzyme and the buffer results in a product which reacts in turn and in a second step, with a colorimetric developer, chromogen gene.

These test elements are deposited inside the syringe body or inside the AMR polymer reservoir.

They are deposited lyophilized or liquid or grafted on or in the wall of the polymer of cavity A or cavity B, on or in the filters of cavity A or cavity B, they can be structurally combined in the molecule of the polymer from cavity A or B or in the filter molecule.

Often the enzyme is sufficient, sometimes enzyme and coenzyme are preferable; Sometimes still, the buffer ensures an optimal ionic strength for the good progress of the reaction.

B. Filters or membranes arranged in the lumen of the syringe body or AMR.

F1 filter:
The AMR or syringe must have a filter to separate the serum from the red blood cells.

The filter, F1 is placed opposite the needle base. It is integrated into the structure of the device. It is inside:
of the AMR reservoir light, at A. (Fig. 5)
From the syringe body lumen, at A (Fig. 5, Fig. 6)
It filters the aspirated blood. It rids the aspirated blood of the red blood cells retained in the structure of the filter, it lets the serum pass.

F2 filter:
An F2 filter separates the microreservoir from the AMR (Fig. 5) into 2 cavities, A and B.

A filter F2 separates the body C of the syringe into 2 parts A and
B (Fig. 5, Fig. 6).

It makes it possible to filter the product of the enzyme-coenzymetampon reaction, by reversing the AMR or at the end of the piston stroke for the piston syringe.

MODIFICATIONS OF THE POLYMER AND FILTER.

In cavity A:
On the internal face of the filter F1 of the cavity A of the AMR (Fig. 7, Fig. 5) or of the plunger syringe (Fig. 6, Fig. 5), either in F1 ′, the enzyme is deposited and the co-enzyme.

The enzyme and the coenzyme can be grafted on the internal face of the polymer of the cavity A or even be included in the structure of the polymer, even at the molecular level or be an integral part of the structure of the filter F1.

The buffer is deposited in lyophilized form in cavity A, for the plunger syringe and for the AMR and more precisely in
F2 'that is to say on the internal face of the F2 filter on the cavity A side of AMER or the plunger syringe. The buffer can be grafted onto the internal face of the polymer in cavity A or even be included in the structure of the polymer, even at the molecular level or be an integral part of the structure of the filter F2.

The buffer dose is adjusted for a biological volume of 3 drops to 100 microliters.

In cavity B:
The colorimetric developer is grafted onto the internal face of the AMR polymer (Fig. 5, Fig. 7).

On the polymer of the plunger syringe, (Fig. 6, Fig. 5) is grafted the colorimetric or chromogenic developer (Chrom), or other development system. Cavity B is closed at O.

OVERVIEW OF MODIFIED MEDICAL INJECTION DEVICES
PATENTED.

AMR, FIG. 7.

The modified and patented micro-reservoir needle includes:
A needle (Aig) 30/100 to 40/100 mm in diameter with
a base in (EM) 0.5cm to lcm in length and a length
useful variable needle.

A deformable flexible polymer (PS) microreservoir (R) of
100 microliters in the example given, but which is
variable, without piston.

Inside the tank (R), a filter in F2 which determines 2 cavities A and B; It is impregnated with the buffer grafted in F2 ', when it is not also grafted on the polymer of the internal face of the cavity A.

The cavity A carries, in the portion opposite the base of the needle, a filter F1.

The position of the enzyme and co-enzyme are variable.

They can be free in lyophilized form in cavity A.

They can be in liquid form at A or grafted on the internal face of the wall in flexible polymer or integrated into the molecular structure of the polymer of cavity A.

The filter F2 carries the buffer at F'2.

The buffer can also be present in lyophilized form.

In this case, the enzymes and coenzymes, to avoid their degradation by the buffer, even lyophilized, will be present on the wall, while being protected by a first polymer mesh of the wall.

The cavity B carries, grafted on the polymer of its internal face, a chromogenic developer in general, assaying the product of the reaction mainly by colorimetry (ex quinone imine)
The plunger syringe. Fig. 6 and Fig. 5:
The base (EM) of the needle (Aig) is fitted into the body of the syringe (C).

The body (C) of the syringe is closed at O.

The F2 filter divides the syringe body into A and B.

The relief RL supports the filter F2 and accentuates the separation of the cavity A and B.

In the cavity A, opposite the fitting of the needle on the body of the syringe, there is the filter F1 on the surface of which is deposited the co-enzyme and the enzyme.

The handle (M) activates the piston (P). The piston play is blocked by the relief RL, it evolves in the cavity A and separates it into 2 parts.

The buffer is grafted in F2 ′ on the filter F2 or present in lyophilized form in A or in liquid form in the piston P, output in Y, the diameter of Y is adjusted so that the quantity is released in proportion to the pumped volume.

In the cavity B is the chromogen in lyophilized form when it is not deposited or grafted on the wall on the polymer wall of the cavity B or on the surface of the filter F2, side cavity B.

Remember, both for the AMR and for the plunger syringe, that this order is not immutable and that the main thing is to be able to have in the cavity A the enzyme, the co-enzyme and possibly the buffer without take into account the grafting method.

Let us also remember that the main thing is to be able to have in the cavity B a colorimetric developer especially making apparent the result of the reaction of the cavity A, as well for the AMR as for the syringe with piston.

BIOCHEMICAL OPERATING MODEL OF THE DEVICES
MODIFIED AND PATENTED INJECTION. with an example of a parameter to be measured: blood sugar.

We will use the Grinder method which measures sugar by a single enzyme, glucose oxidase, abbreviated as GOD.

The result of this serum blood-GOD reaction is hydrogen peroxide.

Hydrogen peroxide mixed with a developer, quinone-imine, gives a colored derivative.

Glucose oxidase is present in the cavity A, grafted on the internal surface of the polymer of the wall or on the filter F1.

The result of the reaction of blood glucose with GOD is oxygenated water which accumulates in cavity A and which passes into cavity B.

Quinone-imine is present in the cavity B, grafted on the internal surface of the polymer of the wall or on the filter F2, but on the side B side.

The reaction between quinone imine and hydrogen peroxide at B gives a pink color derivative whose coloring intensity will give the blood glucose level.

PRACTICALLY,
With the AMR: 2 drops of blood are aspirated, after disinfection and puncture of the finger pulp, by releasing the two-way pressure exerted on the deformable polymer reservoir of the AMR.

The F1 filter, filters the blood, retains the red blood cells, which are useless in our assay, and only lets in the serum which then crosses F1 'and passes into the cavity A.

When it reaches cavity A, the serum reacts:
with the enzyme, GOD or glucose oxidase for example, grafted
in the wall of cavity A and
the possible coenzyme grafted in F1 '.

The result of the reaction is hydrogen peroxide which collects in cavity A.

The AMR is then reversed, tank down.

The product of the reaction of the coenzyme and the enzyme, namely hydrogen peroxide, will pass through the F2 filter into the cavity.
B or it is in contact with quinone imine, grafted on one of the walls or in lyophilized powder in cavity B.

Large molecules that could react with quinone imine or interfere with the steric hindrance reaction are stopped by F2.

The appearance of a pink color in cavity B testifies to the presence of sugar.

Its dosage can be read on a scale.

With the plunger syringe,
The few drops of blood are aspirated using a suitable needle of 30/100 to 40 / 100mm in diameter and 5mm to 20mode in length. The needle has been studied both in its bevel and in its surface to make it painless.

Arrived in the cavity A, after having passed through the filter F1 and F1 ', the blood reacts with the enzyme and the co-enzyme, possibly with the buffer which is evacuated through the orifice Y of the cavity housed in the piston P .

The piston gradually rises towards the relief (RL) to allow the product of the reaction serum on the one hand and enzyme, co-enzyme and buffer on the other hand to pass through the filter F2 to find itself in the cavity B.

In cavity B, the reaction product of cavity A reacts with the chromogen to give a product whose coloration will depend on the level of sugar it contains and which will be assessed using a color scale.

Claims (16)

 Claims 1) Sampling device, for self-detection and self-dosing, in one time of a biological or mineral parameter, consisting of at least one reservoir and one needle, of the plunger syringe or micro-reservoir needle (AMR) type characterized in what it contains in the reservoir of membranes or filters (F1 and F1 ', F2 and F2'), reagents (Enzyme, Coenzyme, Buffer) and chromogenic developers, to react chemically and mechanically with the biological or mineral product sampled by the device to detect and measure there extemporaneously the desired blood, serum or mineral parameter. 2) Device according to claim (1) characterized in that, in the body (C) of the plunger syringe and in the reservoir (R) of the AMR, a filter (F1) is integrated, located opposite of the base of the needle: it retains, thanks to the diameter of the pores of its structure, the red blood cells of the whole blood aspirated by the needle (Aig) and lets the serum pass into the cavity (A). 3) Device according to claim (1) characterized in that in the body (C) of the plunger syringe and in the reservoir (R) of the AMR is integrated an F2 filter: it divides the syringe body (C) and the reservoir (R) in two cavities (A) and (B) where the two successive biochemical reactions take place and it allows the useful product resulting from the reaction which takes place in the cavity (A) to pass, thanks to the diameter of the pores of the structure of the filter F2, in the cavity (B). 4). Device according to Claim 3, characterized in that, to facilitate the succession of chemical reactions, the enzyme and the coenzyme are deposited in the cavity (A) of the body (C) of the plunger syringe and in the cavity (A) of the reservoir ( R) AMR: they allow the parameter to be detected. 5) Device according to claim 3 or 4 characterized in that the reagents of the cavity (A) are deposited in lyophilized form in the cavity (A). 6) Device according to claim 3 or 4 or 5 characterized in that the reagents of the cavity (A) are grafted on the surface of the polymer of the cavity (A).  7) Device according to claim 3, 4, 5 or 6 characterized in that the reagents of the cavity (A) permeate or are grafted on the faces of the filters (F1) and (F2). 8) Device according to one of the preceding claims, characterized in that the reagents of the cavity chemically combine with the molecules of the polymer in the cavity (A) or with the molecules of the filters (F1, F2). (A) 9) Device according to claim 1 characterized in that the buffer is deposited on the underside of the filter (F2), at (F2 ') of the cavity (A) of the body (C) of the plunger syringe and of the reservoir ( R) of AMR. 10) Device according to claim 1 characterized in that the tampon is in lyophilized form and is deposited in the cavity (A) 11) Device according to claim 1 characterized in that the piston (P) of the piston syringe contains the buffer which will escape through an orifice (Y). 12) Device according to claim 1 characterized in that the developer or the chromogen of the cavity (B) is in the wall of the polymer. It is grafted either on its internal surface or chemically combined with the molecules of the polymer. It allows the revelation and the dosage of the parameter. 13) Device according to claim 1 characterized in that for the plunger syringe, the clearance of the piston is blocked by the insertion of the membrane (F2) on the inner wall of the body of the plunger syringe. 14) Device according to claim 1 characterized in that the syringe body of the plunger syringe is closed at (O). 15) Device according to claim 1 characterized in that the AMR or syringe sampling needle is of variable dimensions both for the length and for the diameter. 16) Device according to claim 1 characterized in that the AMR reservoir or the body of the plunger syringe is of variable dimensions, depending on the parameter to be dosed.