Device for blood sampling and simultaneous quantitative determination of blood analytes

The invention relates to a device with which the removal of a Blood sample and the quantitative determination of one or more blood constituents can be summarized in a single step.

There are numerous devices for piercing the human skin and known for collecting blood by suction. For example, in European Patent 0622046 B1, a suction or vacuum device for blood collection is provided, which in the human skin removal pierce a predetermined amount of blood at high speed and can prevent a mixing up of the collected blood.

From international patent application WO 01/28423 are also a Lancing device and a method for collecting blood from tissues known in the depth of the needle and controls the amount of blood by applying is stimulated by pressure.

Such devices have the advantage that a blood sample and then is possible, if the density of fine blood vessels in the skin is low, because the blood is sucked or drawn through a vacuum. Disadvantage of the known blood collection apparatuses is that the removed then transfer blood to a test strip or in a measuring instrument must be, which errors occur and complicated and time consuming Procedures are required. In addition, the blood collection is by the conventional method almost always associated with pain and is perceived by patients as unpleasant.

It was therefore the object that required for blood tests to reduce considerably volume of blood and quantitative determination of the Blood analytes free of any measurement errors and considerably perform faster in that blood and implementation of Detection reaction and possibly blood tests in a single operation be performed. In addition, the task presented, through the use of particularly thin microneedles the subjective pain of the patient significantly reduce.

This object is achieved by a device for collecting blood and simultaneous Performing the detection reaction of analytes in blood, consisting of a handle 1 and a sensor unit 2, said<sl><li>a) the sensor unit 2 comprises a microneedle 3 that in an elastic Membrane 4 is fixed upon application of pressure or forces on the Membrane penetrates the skin and the release of pressure or forces the puncture site, forming a vacuum in the Sensor unit exits again, whereby blood is drawn into the sensor unit is that there with a sensor system, a physical or chemical Property change of the sensor system causes.</li><li>b) the handpiece pneumatically, mechanically or electro-mechanically on the acting diaphragm of the sensor unit</li></sl>

The sensor unit used in the invention not only allows the determination a single analyte, for example, the determination of glucose in Blood, but can vary depending on the built-in sensor system to other Analytes and even for the simultaneous determination of several different Analyte are used by the sensor unit in a plurality of different Sensor systems are inserted. In an advanced Embodiment, consisting of handle and sensor unit Device be directly integrated into an analysis system, with the For example, the color changes in fluorescence behavior, the electrical conductivity, or other chemical or physical Sizes can be registered.

The sensor unit of the invention is generally for single use determined, but may also occur in inserting a plurality of sensor units, z. B. a rotatable feeding unit for the blood several times for the determination of the same analyte are used. They can be connected to the handle and also slightly away from him after every measurement will.

The device is in the following illustrations Individual shows. These representations are only exemplary and should not be construed as limiting the technical embodiment.

Show it:<dl tsize="14"><dt>Fig. 1</dt><dd>an overview of the device according to the invention consisting of a handle 1 and a sensor unit 2;</dd><dt>FIG. 2</dt><dd>the flow of blood and the performance of the Detection reaction and the external determination of the analyte in eight sub-steps;</dd><dt>Fig. 2A</dt><dd>baseline condition;</dd><dt>FIG. 2b</dt><dd>the sensor unit is snapped;</dd><dt>Fig. 2c</dt><dd>the tensioning of the spring;</dd><dt>Fig. 2d</dt><dd>the placing on the skin;</dd><dt>Fig. 2e</dt><dd>the piercing phase;</dd><dt>Fig. 2f</dt><dd>the suction phase; </dd><dt>Fig. 2g</dt><dd>the measurement;</dd><dt>Fig. 2h</dt><dd>the discharge of the spent sensor unit.</dd><dt>Fig. 3 Fig. 3a</dt><dd>the handset with the sensor unit; the handle section, consisting of two sleeve parts with different Functions with attached sensor unit;</dd><dt>FIG. 3b</dt><dd>Sectional view of the handpiece with an attached sensor unit;</dd><dt>Fig. 4</dt><dd>a detailed view of the snap-in / ejection device;</dd><dt>Fig. 5</dt><dd>a detailed view of the triggering mechanism;</dd><dt>FIGS. 6a-e</dt><dd>Sections through a plurality of differently designed sensor units;</dd><dt>Fig. 7</dt><dd>suitable for several different analyte sensor unit;</dd><dt>Fig. 8</dt><dd>a sensor unit with a rotatable feeding of the blood, by a repeated measurement of the same analyte, or also different analytes at different times, it is possible is;</dd><dt>Fig.9</dt><dd>an apparatus according to the invention, wherein the piercing depth by changing the air pressure over the elastic membrane can be varied;</dd><dt>Fig. 10 and 11</dt><dd>Sensor units with devices for filtration or Reservoirs for reagents or washing solutions; </dd><dt>Fig. 12</dt><dd>a sensor unit with a mounted instrument with Reagents or rinsing solutions from relevant can be metered storage vessels from the meter.</dd><dt>Fig. 13</dt><dd>a sensor unit with attached heat block for thermal Pretreatment.</dd></dl>

The functioning of the device according to the invention will in the following Manner described in more detail:

Fig. 1 shows a specific embodiment of the device according to the invention, the the basic mode of operation clear. The device consists of a back-to-use hand part 1, in which the functional units for the Drive are accommodated, and of a sensor unit 2, the microneedle a 3 contains an elastic membrane 4 and a sensor system. 5 The mainly disposable, sensor unit 2 may of are connected at the bottom with the handle, eg., by a Snap 13 or removed by a discharge edge 14 again will. The hand-held part includes the driving part for the construction of the pressure on the membrane acts and moves. Fig. 1 shows an embodiment of the Handpiece for actuating the membrane consisting of the spring 6, piston 8, Vent hole below 9, magnet vent above 11 and Trigger 7. The quantitative evaluation is primarily an external Handheld instrument 10 made.

Flow of blood collection and the quantitative measurement

The flow of blood and the quantitative measurement is reviewed in Fig.2 shown.

Initial state, Fig. 2a

Fig. 2a shows the initial state with the back-to-use handset and the sensor unit, which primarily in a sterile package is accommodated and intended for single use.

Sensor unit is snapped, Fig. 2b

By means of a holding device, for. Example, with a snap closure, the Sensor unit taken from the butt.

Tensioning of the spring, Fig. 2c

The plunger in the handle is moved up and stretched the spring. On on the periphery of the handpiece befindlicher trigger locks the spring in front of it to relax. The pressure compensation openings loading and air out the interior of the handpiece.

Placing on the skin, Fig. 2d

The sensor unit used in the hand-held part is at the skin surface placed.

Lancing phase, Fig. 2e

By pressing the shutter button, the spring is released and the piston moves down. is between the piston and the elastic membrane by the rapid movement of the piston, a compressed air space built up. In the upper hand part air can flow through the large top Vent hole penetrating. The elastic membrane deforms and the microneedle pierces the skin. The air within the sensor unit is passed through lateral slots outwards. These slots may also serve as Openings be provided with any cross-section and closing elements included having a valve function and, for example, only after Open exceeding a predetermined pressure difference.

Suction phase, Fig. 2f

The small lower vent hole escapes the compressed Air. After reaching the maximum penetration depth relaxing the elastic Membrane again and moves back to its initial state. It is built up a negative pressure within the sensor unit to the blood and Sensor system passed. A chemical, biochemical or physical Reaction takes place in this sensor system. The result is a physical or chemical property change of the sensor system.

Measurement, Fig. 2g

After the suction phase, the sensor unit, usually with the coupled hand part, to a measurement and evaluation unit, a preferably Pocket device plugged. One or more readings are displayed.

Shedding, Fig. 2h

After the measurement, the sensor unit is removed or can for additional blood tests are used. In general, the sensor unit means a shedding ability such as a discharge edge, from the butt away. The handset is now by plugging a new sensor unit Use for another measurement ready.

FIG. 3a shows a division of the sleeve, by rotating the upper Sleeve part 16, the screw tightened with the spring 12 and simultaneously electrical energy can be obtained by a corresponding piezoelectric element can. However, the generation of electric power can also electromagnetically be done by a small magnet, which has the advantage that then the way while pressing the spring can be exploited. Preferably the electrical energy but when releasing the spring, during the won lancing phase. The generated power can then for Example for verifying the sucked amount of sample, or for the Supply of energy-autonomous sensors. The lower part of Sleeve 17 can be moved downward and thereby the dropping of Sensor unit permit.

In the construction shown in Fig. 3a is a pneumatic drive with pre-stressed Spring used. The spring is in this case by means of a rotary, pull or Printing mechanism cocked. When triggered, creates a compressed Gas chamber which acts on the elastic membrane 4 of the sensor unit.

Furthermore, there is the possibility of a pump a liquid pressure or to exert a gas pressure via a compressor to the sensor unit. However, electrical energy is necessary for both variants, which in the simplest Case would have to be supplied by batteries. In contrast, it is viewed just as an advantage of the device according to the invention that they without the power of batteries manages.

Other ways to drive the spring are that the spring force without a gas cushion directly on the elastic membrane 4 of the sensor unit acts.

However, the pressure force can also have a micromotor or a micro-engine / gearbox unit be applied, which directly on the sensor unit acts. The Necessary for energy must be externally or via an electrical Storage unit are supplied. Although this would the invention Device are structurally larger, however, the use of an engine would be for Devices with high throughput, for example in hospitals for can get used quite reasonable.

Finally, there is also the possibility of an installed gas cartridge in the handle 1 to exercise dosed by a button pressure surges on the sensor unit. The functionality of the device but then requires the occasional replacement of gas cartridges.

In Fig. 3b shows a drawn complete blood sampling device in the Inside the sleeve lying threaded spindle with a spring 12 which after loosening of the Release 7 drives the piston 8 downward and thereby the above the elastic Membrane of the sensor unit located air column compresses. or directly acts on the elastic membrane 4 and thus the microneedle 3 in the skin drives.

The device of the invention preferably has the size of a pen.

Fig. Figure 4 shows details of the mounting of the sensor unit on the handle with Help a snap closure 13 a discharge edge 14 can also be seen, through which the sensor unit by moving a sleeve 17 of can be pushed out to the handset.

Fig. 5 shows a per se conventional trigger mechanism, in which by operating the shutter 7 of the piston freely given and pressure on the elastic Diaphragm 4 of the sensor unit can be exerted.

Figure 6 a - e. Show various embodiments for single use Sensor unit in detail views. The elastic membrane 4 in the fortified microneedle 3 penetrates under the influence of external pressure on the elastic membrane into the skin. Here the air escapes, where z. B. the lateral annular channel such as a valve effect, which is a passage of air in only one Direction allows. The needle runs upon release of external pressure back again, at the same time a negative pressure is created in the sensor unit, which draws the blood into the sensor unit. There, the blood is first the filtering system 18 filtered before with the sensor system 5 in contact comes.

Fig. 6b shows a slightly different embodiment of the sensor unit, wherein the flexible Membrane is locked into the injection molding part. Upon exercise of external Pressure on the diaphragm, the air escapes from the side of the sensor unit by the Latch. When relaxation of the diaphragm in the sensor unit Under pressure builds up which sucks the blood from the tissue. Another Embodiment is illustrated in Fig. 6c, wherein a flat elastic Membrane and a corresponding depression are used, the a Varying the volume analogous to the domed membrane allow.

The membrane may alternatively held by a spring or a bracket in the form of be, as shown in Figs. 6d and e.

Fig. 7 shows an arrangement in which in the sensor system several different Detection systems for different analytes are arranged, wherein either the analytes simultaneously or in a temporally and spatially predetermined order can be placed.

Fig. 8 shows a sensor unit for multiple use. Through a rotatable engaging blood supply channel, the blood flow in each case only one sensor system passed. After the measurement of the analyte to the feed channel rotates by one grid position further and opens the blood channel to next sensor system. In this way, a sensor unit for the repeated Determination of the same analyte can be used.

9 shows a device for adjusting the insertion depth by changing the air pressure on the elastic membrane of the sensor unit by opening different sized holes in the lower handle peripheral. A large opening lets the air pressure between the piston and diaphragm does not rise so high such a smaller opening. The force on the diaphragm, and thus the Penetration of the microneedle into the skin can thus adjust the air pressure. The inner cylinder of the handle has different sized holes on Extent. The outer cylinder has a bore. Both cylinders slide tight successive. By rotation of the outer cylinder, the corresponding Internal bore open.

Figs. 10 and 11 show further developments of the sensor unit in which the occurring after the stinging and sucking the blood test method only takes place after an appropriate workup of the sample. In the simplest Case, this may be a simple filtration of the blood for the separation the cellular components act. It can, however, also has a filter matrix 18 is inserted will contain the substances for sample preparation. This is in Fig. 10 shown.

In addition, storage vessels 19 may be provided, the substances to prepare contain the blood sample and / or for rinsing, as shown in Fig. 11, these substances, for example by the action of pressure over Valves and diaphragms, are released. In both cases, by a Resistivity the correct wetting of the sensor matrix ensured be, wherein the power supply with a built-in handle System for electricity generation (eg:. Electromagnetically or with a Piezo element) is carried out.

The necessary rinsing solutions and reagents for sample preparation can also be metered from the meter 10, as shown in FIG 12.. Fig. 13 shows a sensor unit with attached thermostatic unit to to pretreat reagents or rinsing solutions or thermally biochemical reactions cause by cyclic temperature changes.

The quantitative evaluation of occurring in the sensor system biochemical Reaction may be optical, electrochemical or other sensors or Determination methods carried out. As detection methods are in addition to the Fluorescence measurement, for example, the following optical methods can be used: the UV / Vis absorption measurement, Surface Plasmon Resonance (SPR), the IR spectroscopy, ellipsometry, and the colorimetry. As electrochemical Assessment methods amperometry and coulometry into consideration. Other methods such as the Surface Acustic Waves (SAW), quartz oscillators, Impedance measurements and cantilever are other recommended methods. However, of particular importance the quantitative determination of the analyte by fluorescence measurement.

Fig. 2g shows an optical evaluation of the sensor system with the aid of a external device. The sensor unit after sucking the blood of the external optical device held, the transparent layers on the Sensor unit enable optical scanning of the sensor system 5th In Analogously, an evaluation for example with a electrochemical sensor system occur.

The detection of the sensor signal is also an invention in the Device meter even possible. Here, the measuring signals transmitted via a transponder to an external evaluation will.

A further refinement of the device of the invention can be carried out in the quantitative determination methods can be achieved in that more blood components in parallel with different measurement methods quantitatively are recorded. For this purpose, in the sensor unit more, for. Example, two different Sensor systems 5 housed, with the same or different Detection methods can be read. Although this a somewhat higher amount of blood is needed is by the spatially close Connection of the sampling point and sensor systems of blood consumption substantially smaller than standard methods, in which a substantially taken greater amount of blood and to spatially separate instruments must be brought. Correspondingly, the burden of pain Patients significantly to application of the device according to the invention lower.

The connected feasible with the inventive device venipuncture with the parallel implementation of the detection reaction of analytes in Blood has over the previously known methods the advantage of largely painless blood sampling using a microneedle and by use of a vacuum. It is also a significant advantage to see that even at the bedside an immediate result of the blood analysis can be made available. Furthermore, it is important that the only disposable sensor unit is always a fresh, germ-free Microneedle is available, since the needle sterile packed in the sensor unit is.

Is further emphasized that the device according to the invention without the Use of electric batteries manages, but rather self-powered Sensors comprising, for example to indicate the filling of the sensor element. The microneedle contained in the sensor unit can with a biased Membrane to be completed, the greater the piercing Opening releases so they are ready to use to completely sterile remains. Also, a cover with a peel-off is possible.

LIST OF REFERENCE NUMBERS

<dl tsize="2" compact="compact"><dt>1</dt><dd>hand part</dd><dt>2</dt><dd>sensor unit</dd><dt>3</dt><dd>microneedle</dd><dt>4</dt><dd>elastic membrane</dd><dt>5</dt><dd>sensor system</dd><dt>6</dt><dd>feather</dd><dt>7</dt><dd>trigger</dd><dt>8th</dt><dd>piston</dd><dt>9</dt><dd>Vent hole below</dd><dt>10</dt><dd>handheld instrument</dd><dt>11</dt><dd>Vent hole above</dd><dt>12</dt><dd>Screw with spring</dd><dt>13</dt><dd>snap lock</dd><dt>14</dt><dd>discharge edge</dd><dt>15</dt><dd>shell</dd><dt>16</dt><dd>Sleeve for rotating</dd><dt>17</dt><dd>Sleeve for the dropping of the sensor unit</dd><dt>18</dt><dd>filter system</dd><dt>19</dt><dd>supply vessel</dd><dt>20</dt><dd>heating block</dd><dt>21</dt><dd>rinse solution</dd></dl>