ES2250007B1 - MICROSYSTEM FOR THE CONTROLLED EXTRACTION AND INJECTION OF SINGLE USE FLUID. - Google Patents

Abstract

Microsystem for the extraction and controlled injection of single-use fluid. The object of the present invention is a microsystem designed for the extraction and injection of fluid in a controlled and single-use manner that consists of a working chamber open to the outside by means of microneedles and an activation chamber that contains a gas with a difference pressure relative to outside pressure. Depending on whether the microsystem is used to suck or inject fluid, the pressure in the activation chamber will be lower or higher than the external pressure. These chambers are separated by a membrane that is destroyed for the activation of the device by passing a current through a resistance located in the membrane, thus weakening the material so that the pressure difference breaks the membrane. The microsystem activation control allows the device to be activated at any time, regardless of when it was installed. The extraction or injection process is carried out in an irreversible way, allowing to simplify the design and lower manufacturing costs. As a consequence of this, the device will be for single use only. Continuous operation can be achieved by grouping a number of these devices into an array and activating them sequentially. One of the applications of this device would be the measurement of glucose concentration in interstitial fluid as well as the injection of insulin, both in a controlled, continuous and painless way. In the same way, it could be used for the measurement of any other chemical substance dissolved in the interstitial fluid as well as the supply of any other type of drug.

Description

Microsystem for extraction and injection single-use fluid controlled.

Object of the invention

The object of the present invention is a microsystem designed for the extraction and injection of fluid from single-use, controlled manner consisting of a work open to the outside by means of microneedles and a camera activation device containing a gas with a pressure difference relative to external pressure. Depending on whether the microsystem is used to suck or inject fluid, the pressure of the Activation chamber will be lower or higher than the external pressure. These chambers are separated by a membrane that is destroyed for activating the device by passing current through a resistance located in the membrane, weakening the material so that the pressure difference breaks the membrane.

Control of microsystem activation allows you to activate the device at any time, regardless of when it was installed. He extraction or injection process is carried out irreversibly, allowing to simplify the design and lower manufacturing costs. As a consequence of this, the device will be for single use only. I know can achieve continuous operation, grouping a certain number of these devices in an array and activating them sequentially.

One of the applications of this device would be the measure of glucose concentration in interstitial fluid as well as the injection of insulin, both in a controlled way, continuous and painless. Similarly, it could be used for the measurement from any other chemical dissolved in the liquid interstitial as well as the supply of any other type of drug.

State of the art

In today's medicine, the control of the measure of the concentration of chemical substances in the blood is essential to increase the quality of life of patients. For example, him control of glucose measurement prevents future complications due to diabetes. This measure should be painless to interfere as little as possible in the life of the patient. It is also It is important to carry out this measurement continuously, in order to control the glucose level at all times, and be able to correct anticipated a glycemic crisis by introducing insulin from controlled way.

Until now, this work has been done by the patient manually. Several times a day a drop of blood through a device that painfully pierces the skin. The glucose measurement is carried out by applying this drop on a test strip, which produces an electrical or colorimetric signal indicating its concentration. Examples of this method are patents EP0078636, EP127958, US5288636.

At present, other solutions that try to improve the measurement technique. To do painless fluid removal find solutions such as the one presented in patent EP1174078, which develops a patch-shaped microsystem. This device It is made up of a tank communicated with the outside through of a microneedle array. The liquid extraction is carried out by surface tension and therefore without any control.

Other solutions are aimed at achieving a continuous measurement, and at present there are techniques such as microdialysis (US6706009). This patent uses a needle of small dimensions and double conduit. Fluid is injected into the skin through one of the tubes. The liquid is collected simultaneously by the other conduit, bringing the chemical substance to be analyzed into solution. This type of invasive technique is usually painful and carries a certain degree of discomfort for the patient.
patient.

An alternative to the use of needles is microporation of the skin. Patent US6142939 uses this technique to open pores in the skin painlessly using a To be. Interstitial fluid extraction is performed later by using another auxiliary device which contains a vacuum chamber and which is placed on top of the perforations. Both devices are of macroscopic dimensions and require the intervention of the patient for their operation, its use being comparable to that of the aforementioned test strips previously.

In the same way, the problem of introducing drugs and medications through the skin should be carried out in a painless and controlled, and ideally continuously. The patent US6589202 develops a dispensing device for doses of medication that is actuated manually. The device contains a series of dispensers made up of a small reservoir and a microneedle array. When the patient operates the mechanism, the reservoir fluid is injected into the skin through of the microneedles and thanks to the pressure exerted by the patient. This device is for manual use and large dimensions.

Patent US6132755 develops a microsystem similar to that of patent EP1174078, but also includes a system more complex liquid injection through microneedles. This system is based on the action of a piston on the liquid you want to inject. The piston is in turn driven by a gas under pressure. Manufacturing this device is complicated and it will cause its cost to increase due to its great complexity.

From all the above it follows that it is necessary to develop a device that performs the measurement glucose concentration and subsequent insulin injection if if necessary. This patent presents a device that can perform these functions painlessly, continuously and controlled way.

To optimize the manufacture of our device, either in size and cost reduction or in integration with other technologies simple elements are incorporated as the single-use valve. Other irreversible valves of the market are US5368704, US6527003 or Miniature one-shot valve (L.J. Guérin).

Description of the figures

Figure 1.- Design of the microsystem object of the invention, consisting of:

eleven.

Module containing a camera work with external pressure and hollow microneedles (15).

12.

Module containing the membrane separator and a heating resistance.

13.

Module containing the camera activation with pressure Pa.

14.

Heating element.

fifteen.

Hollow microneedles.

Figure 2.- Design of the microsystem where They include two metal electrodes and the reactive agent.

14.

Heating element.

fifteen.

Hollow microneedles.

18.

Working chamber

19.

Activation chamber

twenty.

Metal electrodes

twenty-one.

Reactive agent.

Description of the invention

A microsystem designed for the extraction or injection of fluid in a controlled and single use.

The microsystem is composed of two chambers, the activation chamber and the working chamber. The working chamber is open to the outside by means of microneedles, and the activation contains a gas with a pressure difference relative to the Exterior. These chambers are separated by a membrane that is destroyed for device activation.

The activation chamber pressure is will be called Pa. Depending on whether the microsystem is used to suction or inject fluid, the pressure Pa will be less or greater than the external pressure and it will act on the microsystem of the same shape. To suction, the microneedles must be put in contact with the fluid to be extracted. In the case of injection, places the fluid in the working chamber.

The suction and injection mechanism is the same and is based on the pressure difference between the two chambers that form it and their controlled activation due to the passage current through one of the elements.

To produce suction current is passed by the heating resistance so that the temperature of the separating membrane, weakening it. If this is unites the pressure difference that it supports, the result is its break. The fact that the separating membrane ruptures causes tend to balance the pressures in these chambers so that part of the gas in the working chamber passes into the actuation chamber and the suction of the fluid with which the microneedles are in contact.

If it is a question of injecting fluid the only The difference is that as the pressures balance, part of the gas is in the acting chamber goes to the working chamber and therefore there will be an injection of fluid (in this case Pa is greater than the outside pressure).

The present invention performs extraction and injection of fluid in a controlled manner. It consists of the following modules: activation chamber with pressure Pa, working with external pressure, separating membrane, resistance heater and hollow microneedles. Depending on the microsystem treat, of all those that have been specified above, In addition to these modules, it includes a pair of electrodes and a series of chemical substances.

As can be seen in Figure 1, both the structure and manufacture are very simple so that It is a low cost device. The different modules separately and then put together to create the structure complete. The three blocks that will be joined will be: the substrate in the the microneedles have been manufactured, the separator membrane in the which has been deposited a resistance and the top cap.

In the process of welding modules 12 and 13 the pressure of the activation chamber is fixed, since this union is done in an environment at the desired pressure Pa. This design allows size this pressure to ensure extraction or injection of fluid that we need. Working chamber pressure It is fixed from the outside, through the microneedles.

The dimension of the separating membrane two cameras is critical to the proper functioning of the microsystem. The thickness is designed to support the pressure difference between chambers under normal conditions, but that when the temperature increases it weakens and its break.

Microneedles can have different shapes and sizes. Since surface tension is not the driving force behind the fluid is introduced into the microsystem can relax the microneedle dimension specifications. By same reason, the diffusion of the extracted fluid is negligible, although passive check valves can be included to eliminate any loss.

Mode of carrying out the invention

In the first place, the case of the extraction of fluid by this device. In this case the pressure Pa must be less than the external pressure (in certain cases the vacuum). Position the device so that the microneedles are in contact with the fluid to be extracted. The process starts by passing a current through the resistor heater (14). This resistance is located as can be see in Figure 1 between both cameras. When passing current through this resistance, the temperature and the separating membrane begins to decrease its mechanical strength. Taking into account that the thickness of this membrane has been chosen so that it does not withstand the difference in pressure between both chambers at high temperatures, occurs as consequently its breakage. As the pressures balance, part of the gas that is in the working chamber goes to the activation and the suction of the fluid with which they are in contact the microneedles.

One of the applications for which this device has been designed is the extraction and sensing of interstitial fluid. The microsystem would be attached to the skin of the patient by means of a patch so that the outermost layer of the skin is penetrated. As this layer called Stratum Corneum does not contain nerve endings, the microneedles would act painlessly. Once in contact with the interstitial liquid, the extraction of this fluid would be carried out in a controlled manner as explained above. Once the extraction is carried out, the reaction would take place and after it the measurement, for example of the glucose concentration. For this, the appropriate substance would have been included to produce an electron-generating electrochemical reaction. The resulting electrical signal would be measured by the electrodes that this design would incorporate (Figure 2). Another way to carry out this measurement is by carrying out a colorimetric reaction. In this case, the difference would lie in the chemical substances that would have been chosen to carry out the reaction that are different from those that produce an electrochemical reaction and that at least part of the microsystem must be transparent (modules 12 and 13). When the color measurement is carried out using an external instrument, the electrodes in this case would not be included in the design.

In the case of using the device for injection of some fluid the pressure of the activation chamber it will be greater than the outside pressure. The fluid to be injected it is initially housed in the working chamber. He The process is exactly the same as that explained for the extraction, only in this case the pressure difference causes that part of the gas from the activation chamber is introduced into the working chamber and therefore the injection of the fluid into through the microneedles. A natural application of this device would be the painless and controlled injection of some drug via transdermal.

Another application of these microsystems would be a two-dimensional matrix formed by injectors and / or extractors of fluid depending on the user's needs.

In the case of a matrix of microsystems of the same type, i.e. all injectors or extractors, the final design would correspond to one repetition of each one of the blocks. All the upper blocks, in another all the separating membranes and last in another all the microneedles and then the three would join blocks at a time. If it is a microsystem that is the union of microsystems of different types, i.e. injectors and extractors in the same matrix, it would be necessary to manufacture all of each type to the time but independently of the other types. This is due to the fact that in the manufacturing process the pressure of the activation chamber and is different for each type of microsystems, and the chemical substances are also different depending on the type microsystem in question. When the devices are made at the same time, costs would be radically reduced.

Preferred embodiment of the invention

The preferred application of this microsystem is as a glucose concentration meter in the liquid interstitial. In this case, the microsystem would be attached to the skin of the patient using a patch to immobilize it. How has it pursued that the device acts in a painless way microneedle depth would be 20 microns. Once I know set the device would activate at the right time to the extraction of interstitial fluid. The desired amount of fluid would be 1 microliter so a set of possible values of the microsystem would be: 2 mm x 0.25 mm x 2 mm (width, height and depth). Chemicals that must be introduced into the microsystem to obtain the electrochemical reaction are, glucose potassium oxidase and ferrocyanide. The chemical reaction that produced when the interstitial fluid comes into contact with these substances would lead to an electrical signal. To capture this signal should include platinum electrodes. from this one on signal you can get the glucose concentration in the fluid interstitial that is the goal of this app.

Claims (8)

1. Microsystem for the extraction and controlled injection of single-use fluid characterized in that it consists of the following modules, a pressure chamber Pa, another external pressure chamber Pext, a separating membrane, a heating resistance and hollow microneedles, the activation being controlled and single use because it is carried out by passing a current through the heating resistance at the desired time, so that this fact and the pressure difference supported by the separating membrane causes the rupture of the latter and therefore the activation of the extraction or injection process. 2. Microsystem for the extraction and controlled injection of single-use fluid according to claim 1, characterized in that in the extraction the micro needles are in contact with the fluid to be extracted and the pressure of the activation chamber is lower than the pressure exterior Pext, so that when the current passes through the resistance the temperature is increased, producing the rupture of the membrane and when the pressures balance, part of the gas that is in the working chamber passes into the activation chamber and suction occurs. fluid. 3. Microsystem for the extraction and controlled injection of single-use fluid according to claim 1, characterized in that in the injection the fluid is housed in the working chamber, the activation chamber pressure being greater than the external pressure Pext, of In this way, when the current passes through the resistance, the temperature is increased, producing the rupture of the membrane, and when the pressures balance, part of the gas in the activation chamber is introduced into the working chamber, producing the injection of the fluid through the micro needles. . 4. Microsystem for the extraction and controlled injection of single-use fluid according to claim 2, characterized in that two electrodes and a quantity of reactive agent are incorporated in the working chamber that allows obtaining electrochemical measurements. 5. Microsystem for the extraction and controlled injection of single-use fluid according to claim 2, characterized in that a quantity of reactive agent is introduced into the working chamber that allows the obtaining of colorimetric measurements. 6. Microsystem for the extraction and controlled injection of single-use fluid according to claim 5, characterized in that part of the microsystem must be transparent. 7. Microsystem for the extraction and controlled injection of single-use fluid according to claims 4 to 6, characterized in that it is used as a concentration meter for chemical substances and as a glucose meter in the interstitial liquid. 8. Microsystem for the extraction and controlled injection of single-use fluid according to previous claims, characterized in that the microsystem is formed by a two-dimensional matrix of any of the microsystems of the previous claims or a conjunction of them on the same substrate and with ability to selectively actuate the different microsystems that compose it (with timers in the actuation through external control circuitry.