ES2623951T3 - Fluid Handling Devices - Google Patents

Abstract

A device for determining the concentration of an analyte in body fluids, said device comprising: a controller module (14) comprising an actuator; a fluid manipulation device, comprising: a needle as a skin piercing element comprising a fluid collection channel; an inlet chamber (140) connected to a first end of said skin piercing fluid collection channel; a pumping chamber (150); a connection channel (155) connecting said inlet chamber (140) to an inlet end of said pumping chamber (155); a membrane (70) connected to said actuator, said membrane forming a wall of said pumping chamber (150) opposite to said inlet end of said pumping chamber (155), said membrane (70) being deflectable in response to the movement of said actuator; a sensor chamber (100) that includes a sensor for the detection of said analyte; a pumping channel (90) connecting an outlet end of said pumping chamber (150) to an input end of said sensor chamber (100); a waste channel (110) connected to an outlet end of said sensor chamber (100); and a ventilation hole (120) connected to an outlet end of said waste channel (110), characterized in that the actuator comprises a clamp body (210) and a loaded spring clamp pin (200) adapted to work with the clamping body (200), in which the clamping pin (200) is configured to deform the membrane (70) to close the connection channel (155) and stop the flow of fluid from the inlet, and in which The additional movement of the tightening body causes the membrane (70) to compress in the pumping chamber (150) such that the fluid is pumped along the pumping channel (90), in which the removal of the body from squeezing (210) causes the fluid to be withdrawn from the pumping channel (90) in the pumping chamber (150), while the connection channel (155) is still closed by deformation of the pumping membrane (70) by the tightening pin (200) and in which the removal of the tightening pin (200) with u n additional movement causes the connection channel (155) to open and allow fresh fluid to enter the pumping chamber (150), in which the volume of fluid dispensed is at least as large as the combined volume of the connection channel (155) and the sensor.

Description

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(where the analyte is galactose), ketoamine oxidase (where the analyte is a glycosylated protein, for example, fructosamine), a 3-hydroxybutyrate dehydrogenase (where the analyte is a ketone body), Lascorbate oxidase (where the analyte it is ascorbic acid), lactate oxidase (where the analyte is lactic acid), leucine oxidase (where the analyte is leucine), malate oxidase (where the analyte is malic acid), pyruvate oxidase (where the analyte is pyruvic acid ), urate oxidase (where the analyte is uric acid oxidase) and the like. Other oxidizing enzymes for use with these and other analytes of interest are known to those skilled in the art and can also be employed.

Signal production systems also includes an enzyme that catalyzes the conversion of a dye substrate into a detectable product in the presence of hydrogen peroxide, where the amount of detectable product that is produced by this reaction is proportional to the amount of hydrogen peroxide that It is present. This second enzyme is usually a peroxidase, where suitable peroxidases include: horseradish peroxidase (HRP), soy peroxidase, recombinantly produced peroxidase and synthetic analogs having peroxidative activity and the like. See, for example, Ci et al. (1990) Analytica Chimica Acta, 233: 299-302.

Dye substrates are oxidized by hydrogen peroxide in the presence of peroxidase to produce a product that absorbs light in a predetermined wavelength range, that is, an indicator dye. The indicator dye can strongly absorb a wavelength different from that at which the sample or test reagent is strongly absorbed. The oxidized form of the indicator may be the final product colored, faintly colored, or colorless that highlights a change in color. That is, the test reagent may indicate the presence of an analyte in a sample by a colored area that is bleached or, alternatively, by a colorless area of color development. Examples of dye substrates include, but are not limited to, ANS and MBTH or analogs thereof; MBTH-DMAB; AAP-CTA; and the like See, for example, in US Pat. No. 5,922,530 .; 5,776,719; 5,563,031; 5,453,360 and 4,962,040.

Another type of sensor chamber is an electrochemical sensor chamber. Various types of electrochemical systems and methods commonly known in the art of analyte detection and measurement can be employed by the present invention, including systems that are amperometric (i.e., current measurement), coulometric (i.e., measure electrical charge ) or potentiometric (i.e. voltage measurement). Electrochemical sensors include an electrochemical cell that includes two electrodes and one or more reagents of an analyte determination system, where these elements work in concert to produce an electric current in proportion to the amount of analyte present in the chamber. One or more of the electrodes maybe an enzyme coated electrode. The electric current generated provides for a detection of the presence of the analyte and / or measurement of the concentration of the analyte that is present in the fluid within the chamber. Examples of these types of electrochemical measurement systems, which can be adapted for use with the present invention are further described, for example, in US Pat. Nº .: 6,521,110; 6,475,360; 6,444,115; 6,620,310; 4,224,125; 4,545,382; 5,266,179; 5,834,224; 5,942,102; and 5,972,199; as well as W097 / 18465 and W099 / 49307; and U.S. Pat. No. 6,193,873;

6,716,577 and 6,475,372.

As indicated above, in certain embodiments of sensors 100 located in the sensor disk 30 an analyte, such as electrochemically glucose, measures. The fluid can be interstitial fluid. When measuring an analyte such as glucose, the sensor may contain a redox reagent system that includes active compounds or enzyme and redox mediators. A variety of mediators are known in the art, such as ferricyanide, phenazine ethosulfate, phenazine methosulfate, phenylenediamine, 1-methoxy-phenazine methosulfate, 2,6-dimethyl-1,4-benzoquinone, 2,5-dichloro-1 , 4-benzoquinone, ferrocene derivatives, osmium bipyridyl complexes, and ruthenium complexes. Suitable enzymes include glucose oxidase and dehydrogenase (both NAD and PQQ based). Other substances that may be present in a redox reagent system include buffering agents (eg, citraconate, citrate, malic, maleic, and phosphate buffers); divalent cations (for example, calcium chloride and magnesium chloride); surfactants (eg, Triton, Macol, Tetronic, Silwet, Zonyl and Pluronic); and stabilizing agents (for example, albumin, sucrose, trehalose, mannitol and lactose). Other analytes and indicators that can be measured with the sensor include urea, hemoglobin, lactate, alcohol, cholesterol, amino acids, choline, and coagulation factors.

Embodiments include redox reagent systems that can be positioned in any suitable location of a device of the invention, that is, in any flow path of a device. In certain embodiments, the reagent enzyme component may be an enzyme or a plurality of enzymes that work in concert to oxidize the analyte of interest. In other words, the enzymatic component of the reagent system may be formed by a single analyte oxidizing enzyme or a collection of two or more enzymes that work in concert to oxidize the analyte of interest. Enzymes of interest include, but are not limited to, oxidases, dehydrogenases, lipases, kinases, diaphrases, quinoproteins and the like. The specific enzyme present in the reaction area depends on the particular analyte for which the electrochemical cell is designed to detect, where representative enzymes include, but are not limited to: glucose oxidase, glucose dehydrogenase, cholesterol esterase, cholesterol oxidase. cholesterol, lipoprotein lipase, glycerol, phosphate glycerol-3-oxidase, lactate oxidase, lactate dehydrogenase, pyruvate oxidase, alcohol oxidase, bilirubin oxidase, uricase, and the like. In certain embodiments in which the analyte of interest is glucose, the enzymatic component of the reagent system may be a glucose oxidizing enzyme (for example, a glucose oxidase or glucose dehydrogenase).

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The second optional component of a redox reagent system is a mediator, as mentioned above, and which is composed of one or more mediating agents. A variety of different mediating agents are known in the art and include, but are not limited to: ferricyanide, phenazine ethyl sulfate, phenazine methylsulfate, phenylenediamine, phenazine 1-methoxy-methyl sulfate, 2,6-dimethyl-1,4-benzoquinone, 2,5-dichloro-1,4-benzoquinone, ferrocene derivatives, osmium bipyridyl complexes, ruthenium complexes and the like. In embodiments in which glucose is the analyte of interest and glucose oxidase or glucose dehydrogenase are the enzymatic components, ferricyanide mediator, can be employed.

Object devices can be used in a variety of applications, in certain embodiments, object methods are used in analyte determination assays in which the presence and / or concentration of an analyte in a fluid is determined.

The embodiments of the present invention provide a number of advantages, including precise control over the initiation and / or flow of a fluid in a fluid path, where in many embodiments it is automatically achieved. Embodiments of the present methods include repeatedly obtaining (continuously or periodically) a sample of fluid from a subject for analyte determination. Embodiments of the present invention also include stopping and initiating fluid flow in a flow path several times. In this way, the flow of liquid in a fluid circuit can be controlled.

In the use of an object device, a skin piercing element in contact with the inlet chamber of a fluid manipulation device is contacted with a subject in a manner to pierce the subject's skin to obtain the physiological sample . In many embodiments, the skin piercing element is fixed to the input chamber or otherwise in communication with the camera. The fluid is removed from the subject in the pumping chamber of the device, for example, by the inherent pressure of the fluid. For example, the fluid may be continuously or periodically removed from a subject during the period of time that a user retention housing is kept in contact with a part of the subject's body, that is, during the period of time the subject wears a device. The fluid present in the pumping chamber can then be transported to a detection chamber of a membrane deflection device of the pumping chamber, as described above. The fluid can be continuously or periodically pumped from the pumping chamber to an analyte detection chamber, for example, fresh or new volumes of fluid (e.g., freshly collected from a subject) can be continuously or periodically pumped along of a fluid circuit after previously pumped volumes.

Referring to Figs. 1-7, embodiments of the present invention include the insertion of fluid manipulation device 12 into local controller 14. This can be done by a user or fluid manipulation device 12 can be provided already inserted into controller 14. The local controller 14 is then placed in contact with a user so that the sample can be obtained from a user site. For example, the local controller module 14 can be placed on the arm of a user or the like and held thereon by a retainable user support.

A skin piercing element of the fluid handling device 12 penetrates the wearer's tissue. This can be achieved simply by placing the controller in contact with the skin in certain embodiments (i.e., the skin piercing element may extend from the controller in order to penetrate the skin when so contacted).

Communication is established between local controller 14 and remote controller 16 (if used), as a physical or wireless connection. Control commands can be sent between the remote controller 16 and the local controller 14. For example, commands, such as the time of initiation of the pumping chamber can be provided, which in turn extracts the fluid from the user to the device 12.

An actuator, for example, in a local controller 14, which makes mechanical contact with the pump membrane 70 as an access slot 40. In certain embodiments, a peristaltic movement can be provided and the sample, such as interstitial fluid , can be extracted from the user through a skin piercing element (not shown) and into the input chamber 140, connection channel 155, pumping chamber 150, channel edge 190, pumping channel 90, and chamber of sensor 100. Representative samples may include, but are not limited to whole blood and interstitial fluid.

The measurements can then be made by a sensor, located on the sensor disk 30 and aligned with sensor chamber 100. The measurements can be made while the sample is flowing, or when it is stationary. If measurements are desired while the sample is stationary, the actuator can be stopped before measurements are made. For additional measurements, the actuator can be set again in motion, and additional or "fresh" sample can be extracted from the user in the channels and chambers described above. The newly extracted sample displaces the previously measured sample. Previously the measured sample can accumulate in the waste channel 110, while the air escapes through ventilation

120. Alternatively, the previously measured sample can be additionally transported to other sensors in the

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Claims (1)

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