KR20070018881A - Body fluid sampling device - Google Patents

Abstract

The body fluid sampling device further comprises a fluid perforation member 1 having a collection area 9 for receiving body fluid and further comprising a fluid receiving means away from the collection area so that the body fluid in the collection area is initially It is not in contact with the fluid receiving means. The collection zone collects a very small volume of body fluid of approximately 10-500 nl in a very short time of less than 0.5 seconds. The fluid receiving means may have a test area for conducting an assay reaction. Fluid samples from the collection zone are automatically or manually transferred to the fluid receiving means such that the fluid is in contact with the test zone.

Description

Body fluid sampling device {BODY FLUID SAMPLING DEVICE}

The present invention relates to the field of bodily fluid analysis for monitoring the concentration of a specimen, such as blood sugar concentration.

The present invention relates to an apparatus and system for sampling small amounts of body fluids. The body fluid sampling device includes a skin puncture member having a collection area (eg, a fluid path) for receiving body fluid therein. At least a portion of this collection area is open to the outside to sample the fluid. The sampling device, or separation member, includes fluid receiving means that is not in fluid contact with the collection region of the skin puncture member, such that fluid sampled in the collection region does not initially contact the fluid receiving means. A bodily fluid sampling device having an associated collection area, or a system comprising a bodily fluid sampling device and fluid receiving means, may be in a second state in which fluid is conveyed in contact with at least a portion of the collection area. . The concentration of the specimen can be determined based on the signal from the test region of the fluid receiving means.

Body fluid sampling systems for collecting body fluids into disposable members are already known in the art. EP 0 199 484 discloses, for example, a blood collection and analysis system comprising a disposable unit having a capillary for collecting body fluid and transferring the body fluid into the detection zone. Further development of this concept is described in WO 97/42888. The configuration described in this document is essentially implemented by pressing the ring into the area surrounding the collecting area and applying a pumping motion, which is particularly suitable for collecting relatively small amounts of body fluids. EP 0 723 418 describes an analytical system based on small amounts of infiltrating fluid. For this purpose, a very thin hollow needle is inserted into the dermis and pressure is applied to the area surrounding the perforated area so that the penetrating fluid is transferred to the test area through the needle. US 5,801,057 discloses an extremely compact configuration which also uses hollow needles for drawing body fluids. A particular advantage of this configuration is the extremely thin needle that can be inserted into the arm area of the patient with virtually no pain.

The configuration disclosed in US Pat. No. 5,801,057 has already met a number of practical requirements but some of the features are in need of improvement. A common problem with sampling devices according to the aforementioned documents lies in making the hollow needle as small and cost-effective as possible.

For this purpose, body fluid samplers with open collection areas have been considered. In both US 2003/0018282 and US 2003/0028125, skin puncture devices are described which are at least partially disposed in the area of the puncture needle and have an open passageway for body fluid sampling. The body fluid sampled into the collection area is transferred to the test area fixed to the skin puncture member. In particular, in US 2003/0028125, the skin puncture member is integrated with a part of the test strip. In US 2002/0168290, another document describes a similar sampling and testing apparatus that provides a pooling area.

WO 01/72220 describes a fluid sampling and analysis device having skin puncture probes. The puncture probe is in direct fluid communication with the analysis chamber. Thus, this device configuration has the disadvantage that the test chemistry in the assay chamber is compromised by sterilization of the puncture probes that are regularly performed by irradiation with gamma rays. Subsequent sampling and analysis spaces are fixed to each other and therefore must be close to each other to enable efficient sample transfer.

The prior art sampling and testing apparatus describes embodiments in which a sample from a capillary channel is transferred directly to a testing area in fluid contact with the channel. Alternatively, the present invention proposes a bodily fluid sampling and testing apparatus in which the collection area and the testing area are not in fluid contact with the sample being collected. After collecting the fluid sample into the collection zone, in a second step, at least a portion of the collection zone is converted into a second position where at least a portion of the collection zone is in contact with the fluid receiving means receiving fluid from the collection zone. . Alternatively, the fluid receiving means may be moved or both the fluid receiving means and the collection area may be moved.

In a first preferred embodiment, the body fluid sampling device comprises a skin puncture member having a collection area for receiving a body fluid and a fluid receiving means including a test area. Since the fluid receiving means is not in fluid contact with the collection area, the fluid present in the collection area is not in contact with the fluid receiving means. Alternatively, the fluid receiving means may not have an integrated test area and may be in contact with a separate test area for analytical testing.

The second preferred embodiment comprises a device integrated with the skin puncturing means having a fluid collection area, together with the fluid receiving means having a test area. The integrated device is suitable for undergoing physical changes (especially the movement of the collection area relative to the fluid receiving means) such that when driven, the fluid in the collection area is in contact with the fluid receiving means.

A third preferred embodiment relates to an apparatus according to the first preferred embodiment, wherein the apparatus has a movable portion, and at least a portion of the fluid collection region or the fluid receiving means is disposed on the movable portion.

The fourth preferred embodiment relates to the apparatus according to the first preferred embodiment, wherein the body fluid contained in the collection region is moved to the fluid receiving means by electric drive.

The fifth preferred embodiment comprises the apparatus according to the first preferred embodiment, wherein the bodily fluid contained in the collection region is transferred and contacted with the fluid receiving means without using bodily fluid as the conveying means.

According to a sixth preferred embodiment of the invention, the bodily fluid sampling device is in contact with a separate conveying member containing a fluid and then in contact with a test area on the separate member.

The invention is particularly useful for portable testing systems.

In addition, the skin perforation member is preferably a single use only once. It is also preferred to use disposable fluid receiving means which are used only once.

According to one embodiment of the prior art, the conveying means comprises, for example, a capillary tube from the collecting area to the fluid receiving means (eg EP 1 360 931). The bodily fluid is collected in the test area and transferred by capillary drive to contact the fluid receiving means (ie, the collected bodily fluid pushes the sample into the fluid receiving means). This further required a fluid volume, the so-called dead volume, which acts as a transport means for transporting and contacting the fluid used for analysis in contact with the fluid receiving means. This generally means that more volume of fluid must be collected than is necessary for the measurement, and that the dancing volume increases with increasing delivery distance. According to the invention, unlike the prior art, there is no dancing volume required. Ideally, the entire sample volume collected in the collection area is transferred to the fluid receiving means and used for the measurement. Of course, some samples may remain in the collection area, as is often the case with capillaries. In addition, according to the present invention, the body fluid volume to be sampled for measurement does not necessarily increase as the distance between the collection area and the fluid receiving means increases.

Another advantage of the present invention is that thanks to the fact that the skin puncture member and the fluid receiving means are not in fluid contact at first, they can be easily separated into two parts. There is a need for sterilization because the skin puncture member, or at least a portion thereof, penetrates the skin. However, the test area is in most cases sensitive to sterilization. When the skin puncture member and the fluid receiving means are separated into two parts, the skin puncture member can be sterilized separately from the fluid receiving means, thereby preventing damage to the test chemical and thus solving the problem.

The fluid receiving means may itself be a member for transporting the sample to a separate test area, with or without the test area. In both cases, wetting of the test area can, however, be initiated in a controlled manner by the contacting step. This initiation of the test area wetting can control the reaction time (i.e., the time between contacting the test chemical with the sample fluid and reading the test result), which has the advantage of obtaining high accuracy of the specimen determination.

Another advantage compared to prior art sampling devices is that fluid sampling and contact between the sampling device and the testing area can be performed at different locations. Fluid sampling can be made, for example, at the front of the portable device, and contact with the testing area can be made in the portable device. Thanks to the shuttle function of the skin puncture member, it is possible to move the optics or other evaluation means into the housing, which is advantageous given the limited space at the front end. In addition, during the sampling phase, physical separation of the test area from the blood prevents test chemicals from spreading into the human body during sampling. Thus, the present invention has an advantage over the fluid sampling device of the prior art.

One particular application of systems and devices for withdrawing small amounts of body fluid is spot monitoring, in which the concentration of a particular specimen present in the body fluid is determined at a particular time. Such measurements may be repeated at timed intervals to monitor changes in specimen concentration. This analysis using disposable test elements has proved particularly advantageous in the field of blood glucose measurement by diabetes. Excessively high blood sugar levels (hyperglycemia) appearing in diabetics over long periods of time can lead to severe long-term damage such as vision loss and necrosis. On the other hand, if a diabetic is injected with too much insulin, for example, he or she is hypoglycemic, and the diabetic suffers from so-called hypoglycemic shock, which may endanger life. Regular control of blood sugar levels allows diabetics to prevent hyperglycemia and hypoglycemic conditions, and to realize how to regulate their eating habits, physical activity and insulin prescriptions. In addition, in addition to promoting and maintaining the health of diabetics, regular blood sugar monitoring has a significant economic benefit as a whole, as it may prevent the high cost of secondary disease. The causes that hamper the wider and inevitable use of blood glucose monitoring are primarily the pain caused by the collection of the required body fluids and the many handling stages of current commercial systems. In current systems, diabetics or medical personnel must first obtain a drop of blood, which is usually obtained from a finger pad. So-called lancing devices can be used to relieve pain. The lancing device is first mounted, tensioned, placed on the body surface and then triggered. After the lancing process, the user must squeeze his finger to transfer a drop of blood from the punctured wound. Before this procedure, the diabetic must first place the test strip in a blood glucose measurement instrument and drive it. Blood droplets can now be added to the test strip, for example blood glucose measurements after 10 seconds. Finally, the user must discard the used lancets and test strips. The present invention can greatly simplify the blood glucose measurement process.

However, the present invention can also be used for other specimens. In addition, sampled fluids can be analyzed simultaneously or successively with different test areas.

Not only is the simplification of the testing according to the invention advantageous for the current user, but also has the effect that more people with diabetes or other diseases test their blood glucose levels or accordingly more regularly.

The sampling device and system according to the present invention serve to draw out a small amount of body fluid. Preferably, the bodily fluid sample is accommodated in the collection area while the collection area is in the body, i.e. there is no need for blood to leak from the puncture point and the user squeezes his finger to test the blood droplets on his finger. There is no need to move to the area. Of course, it is also possible to use blood leaking from the puncture point. In this context body fluids are understood in particular as blood, fluid between cells, and mixtures of these body fluids. While conventional blood collection systems typically performed sampling on a finger pad, the collection system according to the present invention can also be used to withdraw blood from other locations on the body such as the forearm and palm.

The skin puncture member which draws out a small amount of body fluid in accordance with the present invention has a projection with a sharp end for puncture of the skin. Within at least a portion of the protrusion is a collection area having the ability to collect body fluids. This can be done in particular by capillary action. At least part of the body fluid receiving structure is open. Within the scope of the present invention a capillary structure is understood as a body for transferring body fluids as a result of capillary forces. In the case of capillary channels, when the distal region is in contact with body fluid, the fluid is transferred toward the proximal end of the skin puncture member. Regarding this embodiment, the capillary structure according to the present invention is similar to the open needle structure described in US 2003/0018282 and US 2003/0028125 to which the specification is referred. However, an important difference is that these documents describe microneedles in which the capillary channel is in fluid contact with the test region such that the body fluid contained in the capillary channel is applied directly to the test region and thus initiates the reaction.

Capillary structures in the collection region can be prepared by photolithographic methods as described in US Pat. No. 5,801,057, which is known in the semiconductor art. It is also possible to form channels, grooves, holes and the like that are opened to the solid needle to the outside by milling, etching or the like. Such a structure is preferably made by an etching process such as photochemical milling (PCM). PCM is based on the optical pattern transfer and etching process. PCM is known as micromachining technology.

In addition to the aforementioned method of incorporating the capillary structure into the surface, capillary channels may be made by assembling bodies to create a capillary gap. Thus, for example, two or more solid needles, for example by welding, can be joined to each other such that the contact areas of the solid needles form a capillary channel. Correspondingly, the wires or fibers may be twisted together in the form of stranded wires such that numerous contact areas are created to create capillary channels. The wire or fiber may be made of metal, glass or carbon and may be solid or hollow, for example, it may be necessary to polish the lancet surface to obtain an open capillary. In addition, the capillary tube may not be open to the outside for the entire time, for example, the capillary tube may be open only during the skin perforation step of collecting fluid. One or more layers of material (eg, laminated foil) may also be used in the flat needle to create a skin perforated member having a fluid path in such a way that a capillary gap is formed between or provided in one of these layers.

However, the capillary structure according to the present invention is not limited to capillary channels extending from the end to the proximal end of the skin perforation member. It is also possible to use porous structures or holes for fluid sampling. In the present invention, it is not essential for the capillary to transport the fluid over a visible distance to achieve wetting of the test area. Instead, the collecting area and fluid receiving means move and get closer.

In order to properly sample the body fluids into the channels of the skin puncture member and to improve the sampling rate, it is particularly desirable to use hydrophilic materials for the collection area. Alternatively, hydrophilic coatings may be used in addition to the hydrophilic material.

Because skin puncture devices are introduced into the skin, sterilization is necessary to avoid infection and inflammation. Accordingly, the skin perforation member can be packaged in a sterile manner, for example in a blister. In a preferred embodiment, the tip of the skin puncture member is coated with, for example, plastic to avoid contamination after the skin puncture member is sterilized (eg by gamma rays). Particular preference is given to tip protection as described in WO 01/66010. This tip protective cover surrounding the needle is easy to manufacture and easy to remove, thus enabling automatic removal in the system. The analytical system according to the present invention may comprise an actuator that removes the cap from the tip before skin puncture begins. Alternatively, the skin puncture member is transported to a position where the protective cap is fixed (eg, by form-fit) and the skin cap is removed from the skin puncture member by moving the skin puncture member away from the fixed cap. Can be. Preferably this movement can be carried out by means of a lancing drive or conveying means used between the left and right. An embodiment is also possible in which the protective cap is perforated by a lancing tip of the skin perforation member, for example as shown in FIG. 1 or 6 of WO 0166010.

Alternatively, it is possible to sterilize the skin puncture member immediately before use in a portable device, for example by ultraviolet irradiation or heating.

1 shows one preferred embodiment. A bodily fluid sampling device according to one aspect of the present invention is shown, wherein the collection region comprises a hole or a porous surface, and the received bodily fluid is collected in or on the hole or the porous surface. It is preferred that the sampling device has a hole for receiving three or more samples or, in the case of a porous surface, a hole for even more samples. The skin perforation member shown is made of, for example, stainless steel, silicone or plastic carrier film having a thickness of 0.05-1 mm, preferably 0.2 mm, and has a small hole 2 near the perforation blade 3 of the lancet. Flat lancet (1). The hole 2 may be a through hole or a blind hole, and preferably may have a diameter of 0.01 to 0.5 mm. The number of holes can vary from several to several hundred, three or more are preferred, and more preferably 50-100. Preferred diameters are about 20 μm. Alternatively, the skin puncture element may be a round solid (4) or hollow (5) lancet with sharp edged edges for puncture, as shown in FIG. Round lancets typically comprise three surfaces 6-8. Preferably, the round solid lancet can have a collecting area on its third surface 8. For example, FIG. 2 shows a collection area 9 comprising 70 through holes 2 having a diameter of 20 μm, and FIG. 3 shows seven blind holes 2 having a diameter of 0.15 mm and a depth of 80 μm. ) 4 shows an example of a hollow lancet 5 comprising three elongated through holes 2 in the range of 0.15 mm to 0.35 mm.

Another embodiment of a porous surface for collecting body fluid is an uneven region made on one surface of the surface of the skin puncture member, for example, by polishing. The abrasive grooves form a reservoir for collecting body fluids. Alternatively, the pores can be used to form the collection area. These can be obtained, for example, by creating a sponge surface by, for example, porous coating or selective etching of a lancet material which is a special alloy of a resistant metal and a solvent metal. In particular when using flat lancets, thin fibers of the second material can enter into the surface which can be selectively etched, for example by rolling.

According to the above embodiments, the flow direction of the fluid into the collection region and the flow direction out of the collection region to the fluid receiving means are the same (e.g., in the case of through holes, the hole side in which the fluid receiving means faces the sample inlet). Contact) or its direction of flow may be reversed (fluid receiving means contacting an opening or aperture in which the sample is received).

As already mentioned above, it is advantageous for the capillary channels to be opened outward so that the capillary channels can collect body fluids while the capillary structure is inserted into the body.

The shape of the skin perforation member is relatively insignificant. For example, the skin puncture member may be in the form of a small cube. No special means is usually required to mount the skin perforation member to the drive unit, but it is desirable to have a fixed area at the base of the skin perforation member. Advantageously, the fixation region is formed integrally with another region of the skin puncture member. It is also possible to adopt a configuration of perforation members known for disposable lancets of conventional blood sampling systems. For example, the fixing area may have a taper to which the spring member of the holder of the drive unit is coupled to fix the perforation member. The puncture member is advantageously located in the holder in such a way that good control of the puncture depth is possible (eg by pressing against the stop against the end of the puncture member facing away from the tip). With regard to this holder and the interaction between the holder and the disposable lancing unit, reference is made to the document EP B 0 565 970.

In addition to the skin puncture member, the body fluid sampling device has fluid receiving means that are spatially separated from the collection region of the skin puncture member such that fluid in the fluid collection region of the skin puncture member does not contact the fluid receiving means during filling. However, the fluid receiving means and the collection region are in contact with each other when the initiation of an assay reaction is required after the fluid sample has been received in at least part of the collection region. This contact is primarily a mechanical action in which the channel holding the sample fluid and the fluid receiving means move together. This contact may include pressing the fluid collection region and the fluid receiving means together or may mean a wiping operation.

Separation of the skin puncture member and the fluid receiving means enables embodiments using the skin puncture member as a shuttle for transferring the sampled fluid to the fluid receiving means. This embodiment is particularly preferred when fluid sampling is performed in a spatially confined area (eg, the front end of the device) and the fluid receiving means does not fit well within this confined space. In particular, the latter is the case when the fluid receiving means is fixed to the tape, as described, for example, in EP 0 202 6242.4, US Pat. No. 4,218,421 and EP 0 299 517. Shuttle function,

-Stabbing with a skin perforation member,

Receiving fluid into the collection area of the skin perforation member,

Contacting the fluid receiving means with a portion of the collection area to provide a sample fluid to the test area, and

Enable a testing procedure with detecting a change in test area in relation to the concentration of the specimen.

In a preferred embodiment, the conveying means for conveying or shuttleting the sampled body fluids into contact with the fluid receiving means is made automatically. Preferred embodiments for automatic conveyance include, but are not limited to, electrical, mechanical drive, drive by spring force, such as manual drive by pressing of a slider by a user, or a combination of these drive principles. In particular, an electric motor may be used to obtain the contact.

The above mentioned conveying means is controllable by a control unit which controls the movement of the conveying means, including temporal control and spatial control. By this control unit, it is possible to control the time of filling the sampling member, the timecourse of the transfer, the time of contact with the fluid receiving means, and the time when the test area is evaluated. This control improves fluid sampling and testing, thus increasing reliability.

It is also possible to use a control unit which assists with the conveying means in order to improve the sampling step. In particular, although the skin puncture member is kept in the skin, but the lancing channel is already open and can only be partially withdrawn, body fluids can appear more easily and can be collected by the collection area. The skin puncture member may be turned or moved within the wound to improve the discharge of body fluids. In lancing the skin with the skin puncture member, for example, a conventional spring type lancing unit may be used. As the electric drive for lancing, for example, one described in EP 1101443 may be used. For the movement of the skin puncture means described above, the above-mentioned electrical drive alone or in combination with other transfer means may be used.

In order to improve the sampling by the skin puncture means, a vacuum may be used to draw the body fluids. This vacuum is applied to the skin area where the skin is perforated, or in the case of the hollow sampling needle, a vacuum is applied to the channel of the sampling needle.

The skin puncture member is conveyed to the fluid receiving means such that the skin puncture member is contacted with the fluid receiving means by the aforementioned conveying means. The skin puncture member may also be transferred manually, for example by a user, using a lancet inserted into the skin puncture device, for example, to puncture the skin and collect body fluid samples. This can then be transferred to the measuring instrument in which the fluid receiving means is inserted, and the collection area is brought into contact with the fluid receiving means for conveying a bodily fluid sample.

The test area is particularly easily degraded by moisture. Therefore, the test area must be protected in some way during storage. Skin puncturing means of the present invention can be used to puncture the sealing of the sealed fluid receiving member. This is advantageous because additional means or steps can be avoided in dismantling or opening the seal ring.

According to the invention, it is possible that the skin puncture member is moved to the fluid receiving means, or the fluid containment means is moved to the skin puncture member, or both members are moved.

When employing a magazine with fluid receiving means, there may further be exposing the specific fluid receiving means from the stored fluid receiving means in order to contact the loaded skin puncture member with the sample fluid. When the particular fluid receiving means is evaluated, other fluid receiving means may be exposed to contact the sample fluid on the skin puncture member. The fluid receiving means used may be stored in the same magazine or in an additional disposal magazine, or the fluid receiving means may be disposed of directly, for example manually.

Thus, the automated system according to the shuttle concept has at least one skin puncture member, a drive for driving the skin puncture member for puncturing the skin, and a conveying means for contacting the skin puncture member with the fluid receiving means. The drive and the conveying means for the drilling can be employed in the same drive unit. The conveying means may include, for example, electric drive, spring force drive, for example passive drive by pressing a slider, and a combination of these means. In the manual system according to the above shuttle concept, the skin puncture member and the fluid receiving means are in separate units, and the transfers in contact with each other, for example, after the user punctures the skin with the skin puncture member to collect the sample fluid, the skin puncture member Is made manually by moving the fluid sample into the fluid receiving means and vice versa, contacting the fluid sample with the fluid receiving means.

While it is desirable to move the skin puncture member to the fluid receiving means, it is also possible to move the fluid containment means to the skin puncture member, or it is possible to move both members. The system may also comprise a storage unit for a plurality of fluid receiving means. The system may comprise an exposure unit for continuously exposing the fluid receiving means to receive the fluid. The skin puncture member contacts the fluid receiving means and the fluid sample is transferred to the test area on the fluid receiving means, or the skin puncture member contacts the test area and the fluid sample is transferred directly to the test area. In addition, a fluid receiving means without a test area is used and a separate test area is contacted with the fluid receiving means so that the test area is finally wetted with the sample fluid.

The fluid receiving means is a structure capable of collecting fluid from the collection area of the skin puncture member. The collection of this fluid can be made, for example, by a potential applied between the fluid in the collection area and the fluid receiving means. 5 shows the concept of causing electrical contact of the test area with the sample fluid. The skin puncture member 14 having the collection region 9 is separated from the fluid receiving means by the spacer 11. A high potential is applied between the electrode 12 in contact with the body fluid sample in the collection region 9 and the second electrode 13 in contact with the fluid receiving means. This may cause the fluid sample to move from the collection area to the test area or cause the movement of the fluid receiving means towards the collection area. In both cases, wetting of the test area by the sample fluid can be effected in a very short time frame by applying a potential.

Preferably, since the fluid receiving means has a higher capillaryity than the collection area of the skin puncture member, the fluid is automatically collected during the contact, ie the difference in capillaryity serves as the contact means. In this regard, the fluid receiving means may be made of a fleece or fibrous material that is hydrophilic (at least in the fluid collection area) and is also highly capillary.

The fluid receiving means may have a special area of high capillary material or the like, or the entire area of the fluid receiving means may serve as a receiving means for the fluid from the fluid channel. The fluid receiving means may itself be a test area, which may be covered with a fiber or textile material, or the fluid receiving means is more complex, allowing pretreatment of the sample fluid and / or transfer of fluid to the sensor / test area. do. Pretreatment can include filtration of the fluid sample and / or mixing with the reagent. Alternatively or mechanical force may be exerted on the collecting region and the receiving member together to reinforce the capillary force as the contact means, or overpressure on the collecting region side and / or underpressure on the receiving side, such as a vacuum. This may be applied. In particular, in a collection area comprising a through hole, overpressure may be used on one end of the hole to ensure that at least a portion of the sample contacts the fluid receiving means beyond the collection area through the other end. Mechanical compression means or ultrasonic waves (eg gear drive) are also possible contact means for transporting a fluid sample to the receiving means.

The fluid receiving means comprises a test region having at least one chemical layer containing reagents for detecting the specimen. The reagent causes a detectable change due to reaction with the specimen to be detected. Conventional reagents for detecting glucose are based on, for example, glucose oxidase in connection with a chromogenic redox system. Reagents are well known in the art for optical evaluation of producing color with glucose from body fluids. In addition, reagents are well known in the art of blood sugar test strips that allow electrochemical detection of the specimen. The reagent mixtures used are usually in the solid state and because of their components (eg, aluminum oxide, diatomaceous earth, etc.), they have high capillary properties and can collect body fluids from capillary channels. Since these detection systems are known in the prior art, they will not be described in detail here, see US 5,762,770 and US 36,268.

A preferred embodiment of the body fluid collection system according to the invention additionally has a drive unit which, when activated, moves the skin puncture member from the first position to the second position to perform a lancing operation. Suitable drive units are known in the art of blood sampling systems. The drive unit includes, for example, a spring cocked up by the user and drives the skin puncture member when the spring is released. Particularly advantageous drive units are described in EP B 0565 970.

The system for bodily fluid analysis includes a detection unit. In the presence of an object, if a sensor / test area is used that contains reagents that change color or form color, the system includes an optical detection that includes a light source and a detector for detecting emitted or reflected light. Can have units. In the case of employing electrochemical detection, the system has electrodes in contact with the test area or fluid receiving means. In order to evaluate the raw signal, the system can have an electronic device known in the art for calculating the concentration of the specimen, for example by measuring the so-called Cottrell current (see US 36,268).

With the skin puncture member according to the invention, body fluids can be drawn out while the protrusions are inserted into the skin, or after the punctures, the protrusions can be returned from the body and the body fluids shown on the body surface collected. It is preferred that the protrusions, including the collection area, be in the body during collection of body fluids. In order to collect body fluids, partial withdrawal in which protrusions remain in the body is particularly suitable for sampling in the arm. This is because the small incision in the arm closes up very quickly, so no fluids come out after the puncture or only a very small amount of fluid comes out. On the other hand, the sensitivity to pain in the arm is much less than, for example, the finger, so it is not felt as pain when the protrusion remains in the body.

Also, the withdrawal process can be carried out with a sampling device according to the invention in combination with the above process. In this combined process, perforation is first made, and the protrusions are retracted over a portion of the perforation path and allowed to remain in place for the collection period. Depending on the circumstances, the remaining blood can be almost completely removed so that the user cannot see any blood.

Another important determinant for the effective collection of body fluids is the wettability of the collection area. When a capillary structure made of silicon is used, they can usually be adequately wetted, thanks to the silicon oxide layer on the surface thereof. If metals are used in the capillary structure, they are relatively difficult to wet in many cases. This can be mitigated by various hydrophilicization measures such as silication of the surface thereof. When the wetting angle is less than 90 °, wettability when the liquid in the capillary has a concave maniscus is usually adequate.

In one preferred embodiment of the bodily fluid collection system, the volume of the fluid sample is, ie, less than 0.5 μl, preferably very small, 3-10 nl. Such small volumes can be collected very quickly, for example, using very small holes having a diameter of 20 μm, which generates high capillary forces for rapid filling. Interaction between the skin puncture member and the body while the skin puncture member remains in the body so that a sufficient amount of fluid is received because the time to receive a sufficient amount of fluid sample may be less than 0.1 s, such as 1-10 ms. The time may be less than 0.5 s, such as about 10 ms. Preferably, a sample of a bodily fluid is collected in the body so that no blood is actually visible on the skin. According to the present invention, the geometry of the collection area and thus the volume of body fluids to be collected are precisely defined, for example, it is possible to significantly reduce the risk of oversupply of the fluid receiving means, or the concern of undersupply.

Using the sampling device according to the invention, the receipt of a bodily fluid sample may take less than 0.1 s, preferably 10-15 ms.

Advantageously, display means for displaying sample fluid from body parts can be used in the present invention. The indicator means can be a specially formed finger cone 15 used to enhance sample collection, as shown in FIG. 6. 6 shows an example of the operation and action of the finger cone 15 according to US Pat. No. 6,589,260. As shown in Figures 6A and 6B, the fingertip is pressed over the finger cone by the user, so that the finger cones are pressed together to reduce the inner width 16 of the finger cone. As a result, a part of the fingertip is compressed, so that the internal pressure in the region 17 is increased. With such a configuration, the body fluid sampling in the collection area can be improved and the leakage of body fluid from the body can be minimized. The inner width 16 is ideally within the range of 8 to 11 mm in order to be suitable not only for the finger of a child but also for the finger of a large adult.

According to the present invention, a bodily fluid sampling system with automatic transfer of a collection area to a fluid receiving means is a high speed, one-step operation system that is easy to use, even for older users, disabled users or blind users. Due to the low sample volume collected, there is less risk of contaminating the system components, especially the measuring instrument, thus promoting hygienic disposal of the fluid receiving means used.

Since the volume of the fluid sample is very small while the volume of the skin puncture member is large, for example, by heating the skin puncture member to a temperature of 20 ° to 40 °, preferably to 30 °, the temperature variation of the small sample is preferably reduced. Can be easily maintained below 10 °. In addition, for accurate testing, it is desirable to provide a constant temperature within the range of 20 ° to 40 ° to the testing area.

Advantageously, skin puncture members and / or fluid receiving means are provided in the magazine. One possible embodiment comprises, for example, a skin puncture device having a magazine for the skin puncture member and / or a fluid receiving means magazine, which is a separate unit or is integrated into, for example, a measuring instrument.

Preferred embodiments of the lancet as a skin puncture member and the test strip as fluid receiving means disposed in the magazine according to the invention are shown in FIGS. 7 to 11. 7 and 8 show a magazine 21 for skin puncture members and a concentric outer test strip drum magazine 22 with a separate chamber for each fluid receiving means 23. Each chamber is sealed by a foil, each member having an outer grip to which the drive mechanism of the mechanism is connected to move the member out of the magazine and back into the magazine. A tearable foil 25 seals the chamber. Skin puncture members and fluid receiving means are respectively mounted on respective sliders 27 for guiding the movement of the members. 9 shows a lancet 24 having a collection area moved forward to pierce the skin and collect a sample. During this operation, each sealing foil is torn. 10 shows how skin puncture member 24 moves, for example, to the rear, to a contact position. The fluid receiving means 23 also moves forward, for example, to the contact position. In a preferred embodiment, the fluid receiving means is bent when stored in the cavity and, when exiting the cavity, is in a position as shown in FIG. 10. Thereby, the fluid receiving means comes into contact with the fluid collection region. Alternatively, the fluid receiving means and the skin puncture member are pressed together by suitable driving means. When the fluid receiving means is pressed against the collection area of the member 24, the sample from the skin puncture member is transferred to the fluid receiving means to wet the test area with the sample. The test area is optically read from the back, for example, to confirm sample transfer and to determine blood glucose concentration. 11 shows how the skin puncture member 24 and the fluid receiving means 23 used after the test is completed are returned for storage into their respective drum chambers.

In the fluid sampling system according to the invention, preferably, the collection direction of the bodily fluid sample flow entering the collection region is not parallel and is preferably perpendicular to the main driving / lancing direction of the skin puncture member.

The system according to the invention provides a disposable skin puncture member and fluid receiving means which prevent direct contact of reagent chemicals with the body.

The skin perforation member can be made hydrophilic to enhance the reception of body fluids. Hydrophilization can be carried out over the entire member or in selected areas.

In a preferred system according to the invention, the bodily fluid sample collected in the collection zone is transferred to the fluid receiving means without the use of additional bodily fluid as the conveying means, ie the sample is conveyed mechanically rather than fluid means, preferably Conveyed by electrical or passive means. This method has the advantage that, if necessary, the body fluid can be transferred over a long distance without increasing the dancing volume, and the sample can be transferred to a small specific point, ie the test area. Therefore, the size of the fluid receiving means can be reduced.

FIG. 12 shows another preferred embodiment of the skin puncture member comprising a round, solid lancet 4 having a groove or recess 31, for example milled or etched to form the collection area 2.

13 shows a skin puncture member 14 having a collection area 9 passing through an elongated portion of the skin puncture member. This part is connected to a holder 32 in the form of a frame. This elongate portion has a protrusion 33 protruding from the holder portion 32. At the tip of the projection, a sharp tip 3 is arranged. The sharp tip 3 enables the piercing of the skin surface while poking with the skin puncture member. The collection area 9 is arranged at the front end of the projection. The collection region is an open capillary channel that allows the fluid in contact with the channel in the protrusion region to be moved into the movable portion of the collection region 34 by capillary action. As shown in FIG. 13, the protrusion 33, the movable part 34, and the frame part 32 of the skin perforation member 14 are integrally formed. The skin perforation member 14 can be manufactured by an etching process. As is well known in the silicon fabrication process, wafers of silicon material can be etched to provide devices that include tips and capillary channels. However, for mass production, it is desirable to produce a skin perforated member by etching a thin metal plate. In order to avoid a separate polishing step, it is also particularly desirable to form the sharp tip 3 of the protrusion 33 during the etching process. As can be seen in FIG. 13, after the collection region is filled with sample fluid, there are no reagents or sensors in contact with the fluid channels that immediately receive the body fluid. The present invention proposes to separately arrange a test area or sensor on the fluid receiving means.

FIG. 14 shows the skin perforation member 14 of FIG. 13 together with the fluid receiving means 10 comprising the test area 35. The fluid receiving means 10 is schematically shown. The fluid receiving means 10 is arranged above the skin puncture member 14 on the side where the fluid channel 9 is open to the outside. However, the fluid receiving means 10 is initially separated from the collection region 9 so that the sample fluid in the collection region does not contact the fluid receiving means. Therefore, fluid transfer from the collection area to the fluid receiving means does not occur in this configuration of the fluid sampling device. In the embodiment shown, the fluid receiving means consists essentially of the fixing structure 11 which provides the proper orientation and space of the fluid receiving means with respect to the skin puncture member and the test area 35. In the embodiment shown, the test region includes a reagent that produces an optical signal based on the concentration of the specimen in the body fluid. Since the reagent contains a porous material such as, for example, diatomaceous earth or titanium dioxide, the capillary effect of already sucking fluid from the capillary channel is high. The reagent is applied to the carrier surface. The body fluid sampling device prepares for measurement after the fluid is received into the collection area to fill the movable portion 34. By mechanical driving, the movable part 34 can be bent in the direction of the sensor 35, so that the body fluid disposed in the collection area 9 comes into contact with the test area 35 to wet the reagent. This approach of contacting the sensor with the sample fluid has several advantages over prior art devices.

 The first advantage over the prior art is that the measurement can be initiated at a certain point in time. This means that the time between the wetting of the test area and the measurement of the final signal can be arbitrarily selected. However, the time period is shorter than the drying time of blood in the capillary. Knowing or controlling the reaction time can improve measurement accuracy. It is also possible to measure signals that start immediately after wetting, which makes it possible to monitor the response movement. The evaluation of this initial signal can also be used to improve the accuracy of the measurement results.

FIG. 15 illustrates a bodily fluid test apparatus comprising a plurality of test regions disposed on a test media cassette 10 serving as a fluid receiving means to enable multiple testing (see, for example, EP 1 424 040). . Cassette 10 includes a supply portion for storing an uncontaminated section 41 of the test media tape. A storage portion is used to store the contaminated section 42 of the test media tape. The testing apparatus is a portable apparatus which a user can carry conventionally. The test media tape 10 can be part of a testing device, so that if the test media tape is exhausted, the entire device becomes obsolete or the test media tape can be placed in a disposable cassette contained within the testing device. It may be. In order to detect the test object of the body fluid collected in the test media cassette, the body fluid is applied to the detection region 43 located between the supply portion 41 and the storage portion 42. The testing apparatus further includes a prick unit (skin perforation member 14) for pricking body parts. The stabbing unit is preferably arranged near the detection area.

FIG. 16 shows an embodiment of the invention in which the skin puncture member 1 ′ comprises a collecting region 2 ′ and the fluid receiving means 10 ′ is connected via a hinge 50. FIG. 16A shows a configuration suitable for sampling body fluids by lancing the skin with a collection area 2 ′. The collection region can be selected according to the embodiment described with reference to FIGS. 1 to 4, for example. When the fluid has been sampled, the skin puncture member is drawn out and folded so that the collection area 2 'contacts the test area 35' on the receiving means. In this folding configuration the measurements can be made from below. However, without grounding the device, it is possible to measure the color of the moistened part 51 on the test area 35 'from the top, as shown in Fig. 16C.

Unlike folding the integrated sampling and testing apparatus according to FIG. 16, the skin puncture member and the sample receiving means may be rotated in one plane to contact the sample on the skin puncture member with the test area.

FIG. 17 shows another embodiment for transferring a sample from the skin puncture member 1 '' onto the test area 35 ''. 17A shows a skin puncture member that already has a sampled fluid and is returned into the housing. Since two parts 60, 60 ′ are provided which press the rubber seal 61 on the skin puncture member, the area holding the sampled fluid is sealed from one side. Upon further pressure, the rubber seal is squeezed and transferred from the skin puncture member onto the underlying test area 35 ″. In addition to transferring the fluid by contact or by transferring the fluid by contact, in this embodiment, the fluid transfer is by pneumatic drive. For example, when compared to a device according to WO 01/72220, which also uses pneumatic drive, the relative movement of the skin puncture member and the fluid receiving means 10 '' is used before pneumatic drive takes place. As described above, this allows for the separation of the lancing portion from the testing portion, allowing sterilization without damaging the test chemistry.

17 further shows that sample fluid from a hole in the collection area of the skin puncture member is transferred to an area opposite the testing area. The geometric pattern of the holes in the collection area results in a similar pattern on the test area. In the case of using conventional dry chemicals, the wet area on the test area is initially about the same size as the hole diameter in the collection area, and the fluid moves vertically. In order to isolate the fluid transfer from the optics, it is desirable to evaluate the subject dependent response from the opposite side to which the sample was applied. Therefore, it is desired to achieve complete wetting over the entire thickness of the test area so that even at the bottom of the test area the reaction occurs. Sufficient wetting is obtained, for example, when the thickness of the test area is less than the depth of the hole in the collection area. Preferably, the thickness of the fluid receiving zone of the test zone is 10-80% of the depth of the hole in the collection zone. This means that very small and thin skin perforation members can be used, as will be clearer by the following examples. Today, it is possible to produce dry chemicals with fluid receiving structures of only 10-50 micrometers thick. To ensure proper wetting, the depth of the hole in the skin puncture member should be 50-500 micrometers to collect sufficient fluid volume even if the collecting holes are not completely filled. This means that such a thick or slightly thicker skin perforation member can be used. Therefore, it is preferable that the skin perforation member has a thickness of less than 500 micrometers, and more preferably, a thickness of less than 250 micrometers. The skin puncture means of the present invention can be made with the same roughness as today's lancets that do not sample fluid. The sampled volume of fluid collected is only in the range of nanoliters, but a reliable measurement can be obtained because a suitable dry chemical test area can be obtained.

18 shows a skin perforation member having two parts 70, 70 ′ capable of relative movement. In FIG. 18A, portions 70, 70 ′ are aligned to form capillary channels that receive the sample. The filled device (FIG. 18B) is rearranged as in FIG. 18C. At one end of the channel, the parts move away from each other, so that the sample is concentrated in the area 71 where the parts are still close to each other.

19 shows an arrangement of sealed fluid receiving means 83, sealed against the outside by a sealing foil 88 (eg, alumina laminate). Skin puncture means 84 is disposed in portable device 80. The skin puncture means shown is already filled with the sample and is moved to the arrangement of the fluid receiving means. To perforate the sealing foil, the skin puncture member itself, or, as shown, a separate tip 85 can be used. The tip of the skin perforation member then contacts the test area under the torn sealing foil to transfer the sample fluid. The test object concentration can be measured by the optical device 86 from the lower side as schematically shown. In order to enable optical inspection, a test region is disposed on the transparent support member 87.

Preferred features of the invention are listed below.

The body fluid sampling device includes a skin puncture member having a collection area for receiving body fluid, and a fluid receiving means including a test area and spaced apart from the collection area so as not to come into contact with a fluid in the collection area, wherein the skin puncture is performed. The member has two or more collection areas.

In the body fluid sampling device according to the invention, the collection area comprises a through hole or a blind hole.

In the bodily fluid sampling device according to the invention, the collection area comprises a generally bumpy surface or recess for receiving bodily fluids.

In the body fluid sampling device according to the present invention, the volume of the body fluid accommodated by the sampling device is 3 to 10 nl.

In the body fluid sampling device according to the present invention, the time for holding the skin puncture member in the body for receiving a body fluid sample is 10 msec.

In the body fluid sampling device according to the present invention, the time for accommodating a sufficient amount of body fluid sample is less than 0.1 sec, preferably 1 to 10 msec.

The system for bodily fluid analysis includes a fluid permeation means comprising a skin puncture member having a collection area for receiving fluid and a test area, wherein at least a portion of the collection area is open to the outside and the fluid receiving means is in contact with a fluid in the passageway. Away from the collection area to avoid contact, the system includes an instrument with a detection unit that receives a signal from the test area to determine the presence and / or concentration of the specimen.

In the system according to the invention, the instrument comprises a holder for receiving the fluid receiving means, allowing signal transmission from the test area to the detector.

In the system according to the invention, the instrument has a processing unit which receives a signal indicating that the contact means has contacted the collection area with the fluid receiving means or that the sample fluid has reached the test area.

The system according to the invention further comprises an exposure unit for continuously exposing the fluid receiving means from the magazine containing the fluid.

The calculation method of the test object concentration in a bodily fluid is

a) receiving fluid into the collection area of the skin perforation member,

b) contacting the collection area of the skin perforation member with the fluid receiving means such that body fluid reaches a test area on the fluid receiving means,

c) receiving a signal from the test region, such as a characteristic for the concentration of the specimen, and

d) processing the signal to calculate the concentration of the specimen, monitoring the period during which step b) begins, and calculating the specimen concentration based on the elapsed time.

In the method according to the invention, the monitoring of the signal is initiated in step b) and the timing for calculating the concentration is obtained using the signal variation over time.

Claims (43)

A skin puncture member having a collection area for receiving body fluid, at least a portion of the collection area being open to the outside, and A body fluid sampling device comprising a test zone and further comprising fluid receiving means away from the collection zone and not in contact with the fluid in the collection zone. The bodily fluid sampling device of claim 1, wherein the bodily fluid sampling device is adapted to undergo a physical change during operation to indicate a contact state in which the fluid in the collection region contacts the fluid receiving means. The bodily fluid sampling device according to claim 2, wherein the bodily fluid sampling device has a movable portion and at least a portion of the collection area is disposed in the movable portion. The body fluid sampling device according to claim 1, wherein, by the electric drive, the body fluid contained in the collection region is moved to the fluid receiving means. 2. A body fluid sampling device according to claim 1, wherein the body fluid contained in said collection region is conveyed without using body fluid as a conveying means and is in contact with said fluid receiving means. 2. The body fluid sampling device of claim 1, wherein the collection region includes a hole through which the received body fluid is collected. 2. The body fluid sampling device of claim 1, wherein said collection region comprises a porous surface for receiving body fluids. The body fluid sampling device according to claim 1, wherein the volume of the body fluid received by the sampling device is 0.5 μl or less. The bodily fluid sampling device according to claim 1, wherein the bodily fluid sampling device further comprises display means. 10. A body fluid sampling device according to claim 9, wherein said indicator means comprises a finger cone. A skin puncture member having a collection area for body fluid reception, wherein at least a portion of the collection area is open to the outside, and A fluid receiving means comprising a test area, said fluid receiving means away from said collection area and not in contact with the fluid in said path. 12. The system according to claim 11, comprising fluid receiving means for providing a sample fluid to the test area and contact means for contacting a portion of the collection area of the skin puncturing means. 13. The system of claim 11 or 12, wherein the collection zone receives the body fluid sample while at least a portion of the collection zone is in the body. 13. The system of claim 11 or 12, wherein the collection area is disposed at the tip of the skin puncture member and is fully introduced into the body. 13. The system for analyzing body fluid according to claim 11 or 12, wherein the system for analyzing body fluid comprises means for adjusting the temperature of the test zone to a temperature within a range of 20 ° C to 40 ° C. 13. The body fluid according to claim 11 or 12, wherein the skin puncturing means has a movable portion, and the contact means applies a force to the movable portion to move at least a portion of the collection area into contact with the fluid receiving means. Analytical System. 13. The system of claim 11 or 12, comprising drive means for driving the skin puncturing means into the skin to puncture the skin to obtain a body fluid sample. 13. The apparatus of claim 11 or 12, wherein the contacting means comprises voltage means for applying an electrical potential between the collection region and the fluid receiving means to bring fluid from the collection region into contact with the fluid receiving means. Body fluid analysis system comprising a. 13. The system according to claim 11 or 12, further comprising transfer means for transporting said skin puncture member relative to said fluid receiving means. 13. The method of claim 11 or 12, wherein said contact means comprises ultrasonic means for applying a force to said body fluid sample in said collection region to bring fluid from said collection region into contact with said fluid receiving means. System for analysis of bodily fluids. 12. The bodily fluid analysis system of claim 11, wherein the skin puncture member is held within the body to receive the bodily fluid sample is less than 0.5 sec. A skin puncture member having a collection area for receiving body fluid, at least part of the collection area being open to the outside, Fluid receiving means remote from said collection area and not in contact with the fluid in said path, said fluid receiving means comprising a test area, Conveying means for contacting said skin puncture member with said fluid receiving means, and A detection unit for receiving a signal from the fluid receiving means to calculate the presence and / or concentration of the specimen in the bodily fluid sample. 23. The system of claim 22, wherein the transfer means comprises an electrical drive. 23. The system according to claim 22, wherein said conveying means comprises a spring force drive. 23. The system according to claim 22, wherein said transfer means comprises passive driving. 23. The system of claim 22, wherein the transfer means comprises a combination of electrical drive, spring force drive or passive drive. 23. The system of claim 11 or 22, further comprising a magazine for storing a plurality of fluid receiving means. In the calculation method of the test object concentration in the body fluid, a) receiving fluid into the collection area of the skin perforation member, b) contacting the collection area of the skin perforation member with the fluid receiving means such that body fluid reaches a test area on the fluid receiving means, c) receiving a signal characteristic for the specimen concentration from the test region, and and d) calculating the concentration of the test object by processing the signal. 29. The method of claim 28, further comprising stabbing the skin by the skin puncture member. 29. The method of claim 28, wherein the skin puncture member is transferred to the fluid receiving means by a conveying means such that the skin puncturing means contacts the fluid receiving means. 29. The method of claim 28, wherein the skin puncture member is automatically transferred to the fluid receiving means so that the skin puncture member is in contact with the fluid receiving means. 29. The method of claim 28, wherein the skin puncture member is manually transferred to the fluid receiving means so that the skin puncture member is in contact with the fluid receiving means. 29. The method of claim 28, wherein the skin puncture member is held in the body for receiving the body fluid sample is less than 0.5 sec. As a body fluid sampling method, a) receiving body fluid into the collection area of the skin perforation member, and b) removing the skin puncture member from the body while maintaining the body fluid in the collection area. 35. The bodily fluid sampling method of claim 34, wherein the bodily fluid sampling method further comprises calculating whether a test object exists in the bodily fluid sample and / or the concentration of the test object in the bodily fluid sample. 35. The method of claim 34, wherein step a) comprises collecting a bodily fluid sample in the collection area while the skin puncture member is introduced into the body. 35. The method of claim 34, wherein said body fluid sampling method comprises stabbing the skin by said skin puncture member prior to said step a). In the system for body fluid analysis, A skin perforation member having at least a portion open to the outside and having a collection area for receiving body fluids, A conveying member away from said collecting region and not in contact with the fluid in said path, Fluid receiving means comprising a test area, Conveying means for contacting said conveying member with said fluid receiving means, and A detection unit for receiving a signal from the fluid receiving means to calculate the presence of the specimen in the bodily fluid sample and / or the concentration of the specimen in the bodily fluid sample. Body fluid sampling device, -A body fluid sampling device, characterized in that it comprises a skin puncture member which is open to the outside and has a collection area comprising three or more holes through which the received body fluid is collected. 40. A body fluid sampling device according to claim 39, wherein said collection area comprises a porous surface for receiving said body fluids. 40. A body fluid sampling device according to claim 39, wherein the volume of said body fluid received by said body fluid sampling device is 0.5 µl or less. 40. A body fluid sampling device according to claim 39, wherein the skin puncture member has a thickness of less than 500 micrometers, preferably less than 250 micrometers. A system for sample analysis having a body fluid sampling device according to claim 39, And a fluid receiving means having a test area, wherein a thickness of the test area is 10 to 80% of the depth of the hole in the fluid receiving area of the skin puncture member. .

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