HK1152633B - Rapid blood expression and sampling - Google Patents

Description

Rapid blood expression and sampling

Background

The present application relates generally to the field of collecting and analyzing bodily fluid samples.

Portable blood testing devices, for example for blood glucose, cholesterol, etc., are popular in home diagnostic, medical and/or veterinary settings due to their improved convenience. One significant drawback of portable testing is the pain associated with piercing the skin to collect a fluid sample. Pain can be reduced by penetrating the epidermis at a shallower depth, but less blood and/or interstitial fluid is typically extracted. For the home diagnostic market, consumers want such tests to be painless, convenient, and short-lived, in order to minimally interfere with daily activities. In the current market, non-integrated test products are mainly used, where separate lancets and test strips are used for extracting and analyzing a fluid sample. However, to ensure successful testing, these non-integrated methods typically require relatively large sample volumes, and therefore, they require painful deep incisions. These non-integrated systems are not very convenient and require a significant amount of time to perform successful testing due to the multiple individual steps involved.

Integrated disposable devices have been proposed that incorporate some type of lancet or needle with a testing means, such as a test strip, so that the piercing, fluid collection and sample analysis steps occur almost simultaneously within a single unit. While integrated disposables are more convenient and are capable of collecting fewer blood samples at shallower penetration depths, integrated disposables have not been commercially successful for a number of factors. Integrated disposable devices have not achieved commercial success due to several factors. One major factor is the low successful test rate of current batch integrated disposables. Current testing methods use separate lancets and test strips. In traditional tests, a lancet is used to pierce the epidermis and a separate test strip is used to collect and analyze the sample as a drop of blood forms on the epidermis. With these current methods, if one of the steps proves problematic, other steps or options can be performed so that a successful test can be obtained without having to abandon the entire process. In other words, using conventional non-integrated methods, the user may intervene in the collection process to ensure that a successful test can be performed. For example, the user may re-pierce the skin around the incision and/or squeeze the skin to extract additional fluid without wasting the test strip. In contrast, the various sources of fluid collection failures in integrated disposables are cumulative in nature, such that a failed test results in a total loss of the integrated disposables. Typically with integrated disposable devices, the user gets an opportunity and therefore all of the various steps of piercing the epidermis, withdrawing fluid and analyzing the fluid must be performed without error. If one step fails, the entire test fails and the integrated disposable is often wasted and needs to be replaced with a new one, thereby defeating some of the advantages of the integrated system. It should be appreciated that these test failures may cause the operating cost of the system to be very expensive. Furthermore, the need for multiple attempts to perform a successful test can be annoying to the user.

Therefore, improvements in this area are needed.

Disclosure of Invention

In view of the above problems, the inventors found that: the problem of collecting liquid using an integrated disposable device to achieve high collection success rates is solved by penetrating the epidermis and collecting body fluids from the epidermis before reflex action occurs. The reflex action typically occurs during sample collection in response to pain associated with penetrating the epidermis. For example, when a person cuts his finger, his first response is to evacuate the finger from the source of the pain. While this reflex action is useful in many cases to avoid further injury, it is disadvantageous for body fluid collection and testing. In particular, the user may withdraw or remove his finger or other body part from the collection device before being able to collect a sufficient sample. Furthermore, the fingers or other body parts may become taut due to pain, thereby binding the blood vessels and causing a corresponding reduction in bleeding. Reflex motion can also damage the device and cause liquid to flow out of the device, resulting in unsuccessful testing. On the other hand, by collecting body fluid from the epidermis or other tissue and removing the epidermis penetrating device, such as a lancet or needle, before the reflex action occurs, fluid can be collected with a high success rate.

According to current pain theory, the nerve impulses of pain travel at about 10 meters per second (m/s). Depending on the size, age, health, etc. of the individual, it is expected that the reaction time to sense pain on the finger will be approximately 200 to 500 milliseconds (ms). In tests conducted by the inventors, it was found that: the fastest response time to pain was approximately 150ms for the individuals tested. In addition to perceiving pain, reflex action may occur due to other sensory cues such as visual or auditory stimuli. For example, a simple reaction time to detect the start of a flash is about 200ms to 300 ms. The optimal athlete reaction time to an auditory stimulus, such as to a starter gun of a starter in a track, is typically in the range of about 120 to 160 ms. Based on insights and support of test results, the inventors found that: it is desirable to remove the penetrating member from the incision in about 200ms, and particularly in about 150 ms. In order to provide a safe buffer, it is therefore desirable that the entire puncturing process does not take place for more than 100 ms. It will be appreciated from the following description that by withdrawing the puncturing element within about 75ms of the initial puncturing of the puncturing element, the inventors have collected bodily fluids at a commercially successful level.

Erroneous test results can also be a concern and source for failed tests in integrated devices. As previously mentioned, the fluid sample volume of the integrated device may be relatively small, that is, in the sub-microliter (sub-microliter) range. In one particular example, the sample volume may be from 20 nanoliters (nl) to 200nl, while still achieving accurate test results in a relatively short period of time. These smaller sample volumes enable faster testing, but they are prone to sources of inaccuracy and, as a practical matter, have a lower volume limit for accurately testing fluid samples. The inventors have found that evaporation of liquid during fluid collection and analysis is one source of inaccuracy in sample test results in the sub-microliter or nanoliter range. In these minute test volumes, very slight changes in volume may cause significant differences in analyte concentration measurements. It has been found that integrated devices having open capillary channels are particularly susceptible to fluid evaporation problems. By drawing the sample within 500ms of penetrating the skin and placing the sample on the sample analysis tool, the problem of inaccurate test results for sample sizes less than 1 microliter in an integrated device having an open capillary channel is solved. In other aspects, the fluid is placed within 150 or 200ms to further reduce evaporation, and in another aspect, within 100ms or even within 75ms, which brings further benefits. By placing the collected fluid in this rapid manner, only minimal evaporation occurs, leading to more accurate results.

To achieve a high fluid collection success rate for a short time integrated device, the inventors have found that at least three general factors contribute to successful fluid collection: a tip design of the piercing member; a piercing profile; and the amount of force applied against the epidermis. Furthermore, the inventors have found that the above factors alone do not result in a continuous and rapid fluid collection. Rather, specific combinations and levels of these factors are required. Specifically, the inventors found that: the problem of achieving a high collection success rate for collecting fluid is solved by exerting pressure on the fluid under the skin in order to easily introduce the fluid into the capillary channel having a channel inlet offset from the tip of the penetrating member, and withdrawing the penetrating member from the skin at a lower speed than during penetration of the skin, such that the penetrating member is completely withdrawn from the skin before a reflex action occurs.

Given that the piercing member must collect fluid over a relatively short period of time, the capillary channels in the piercing member sometimes do not fill sufficiently before withdrawing from the skin. It is hypothesized that the viscosity or other characteristics of the collected blood (and/or other bodily fluids) may limit the rate at which the capillary channel may be filled. The problem of collecting a sufficient amount of bodily fluid for testing before reacting to the pain associated with penetrating the skin with the penetrating member is solved by completely filling the capillary channel with the bodily fluid attached to the penetrating member after the penetrating member is withdrawn from the skin. In other words, the inventors found that: it is not necessary that all sample is brought into the capillary channel before the piercing member is withdrawn, but only that the sample within the capillary channel and/or attached to the piercing member is located in a position where it can be drawn into the capillary channel after withdrawal. As previously mentioned, it has been unexpectedly found that the design of the tip of the piercing member affects the success of fluid collection. In one embodiment, the tip of the piercing member is designed such that: after the penetration member is withdrawn from the skin and any fluid that pools on the surface of the skin, the bodily fluid remains attached to the inlet of the capillary channel.

While not previously recognized as a factor in fluid collection speed, it has been unexpectedly discovered that the offset distance of the capillary passage inlet is a factor in increasing fluid collection speed. In a particular aspect, the inlet of the capillary channel in the lancing member is offset a specific distance from the tip of the lancing member. The inventor finds that: if the inlets of the capillary channels are too close, the relative pain caused by penetration into the epidermis is unacceptably high. Furthermore, it was surprisingly found that: in the case of the short penetration times involved, when the capillary inlet is too close to the tip, insufficient sample volume can be collected for the test. Although there is no exact answer, the inventors have several theories to explain this result. One theory is that: the capillary inlet is close to the tip so that only a small pooling area is formed for the fluid under the skin. Another underlying theory is: the relative proximity of the capillary inlet to the tip prevents fluid from adhering to the penetrating member after withdrawal because fluid on the penetrating member is drawn back or adheres to the fluid droplet on the skin and/or to the incision. It is contemplated that increasing the distance between the capillary channel inlet and the tip of the puncturing element will increase the collection success rate, since the collection volume will be larger. However, it has been surprisingly found that the capillary channel inlet is too far from the tip of the puncturing element to be detrimental to the success rate of fluid collection. While the actual source of this unexpected result is not known, in theory this may be due to the capillary channel inlet being too far away so that less fluid from the incision can attach to the capillary channel inlet before withdrawing from the skin. In one aspect, it is found that: the location of the opening or entrance of the capillary channel is from 350 to 600 micrometers (μm) from the tip to provide the desired collection success rate, and in a more particular embodiment, the entrance of the capillary channel is located from 382 to 5730 μm from the tip. In one particular embodiment, it is desirable for the opening to be located 425 μm from the tip. It will be appreciated that the tip design of the piercing member is also beneficial for other aspects of rapid fluid collection.

To achieve rapid and accurate fluid collection, the inventors have also found that pressure must be applied to the epidermis. In particular, it was found that a force of 10 to 12 newtons (N) was required to be applied to the squeeze ring to rapidly squeeze the fluid. Any force greater than 12N applied to the epidermis tends to cause significant pain and/or cause injury. Based on further experiments, the inventors found that: applying a force of 8N produces commercially acceptable results, in some examples the squeeze ring should apply a force of at least 6N, and rapid fluid collection is still feasible. Basically, the blood under the epidermis is pressurized with a certain force against the epidermis pressing the squeezing ring, which allows the pressurized blood to be injected into the capillary channel in a rapid manner.

It has also been found that the penetration profile is a factor that promotes rapid fluid collection. Specifically, it was found that: rapid penetration followed by longer withdrawal (exit) tends to minimize pain and promote fluid collection. The following are found: a constant withdrawal process or a withdrawal process with a specific residence time under the epidermis followed by a rapid withdrawal from the epidermis is suitable for the purpose of rapid fluid collection. In one particular aspect, 3 to 5ms penetration followed by a longer withdrawal time of 70 to 197ms achieves a quick and consistent result. A typical penetration depth of the penetrating member is set to about 1.6mm during penetration, but the actual penetration depth may vary from 0.8 to 1.2 mm.

Other aspects relate to the specific features of the expression member and the specific dimensions of the piercing member to minimize pain and facilitate fluid collection. In one aspect, the tip has an included angle or edge angle of from 20 ° to 40 °, more preferably about 30 °. The shank of the tip has a width of 300 to 700 μm, and in one particular form, has a width of about 300 μm. The penetrating member has a thickness of 50 to 150 μm, and in one particular form, has a thickness of about 127 μm. The capillary channels in the tip are hydrophilic and have an aspect ratio (depth/width) of about 0.7 to 1.6, and in a particular form, the aspect ratio of the capillary channels is about 1.4.

Other features and advantages will be understood from the following detailed description.

Drawings

FIG. 1 is a diagram of an integrated meter system, according to one embodiment.

FIG. 2 is an enlarged top view of a micro-sampler used in the system of FIG. 1.

FIG. 3 is an enlarged top view of the top of the micro-sampler of FIG. 2.

FIG. 4 is an enlarged side view of the top of the micro-sampler of FIG. 2.

FIG. 5 is a cross-sectional view of the micro-sampler of FIG. 2 taken along line 5-5 in FIG. 4.

FIG. 6 is a top view of a micro-sampler according to another embodiment.

FIG. 7 is a perspective view of a compression assembly incorporating the microsampler of FIG. 2.

Fig. 8 is a perspective view of an O-ring compression ring.

FIG. 9 is a perspective view of a negative S-shaped compression ring.

Fig. 10 is a perspective view of a tapered squeeze ring.

Fig. 11 is a perspective view of a brass extrusion ring molded using rubber overmolding.

Fig. 12, 13, 14, 15, 16, 17 and 18 show enlarged perspective views of the micro-sampler at various stages of collection of a bodily fluid sample.

Fig. 19 is a graph illustrating a piercing profile for a slow continuous withdrawal phase according to one embodiment.

Fig. 20 is a graph illustrating a piercing profile at a dwell stage according to another embodiment.

Fig. 21 shows a success rate diagram of an experiment performed using the micro-sampler of fig. 2.

Fig. 22 shows a success rate graph of an experiment performed using the O-ring pressing ring of fig. 8.

Fig. 23 shows a success rate graph of an experiment performed using the negative S-shaped pressing ring of fig. 9.

Fig. 24 shows a graph of the success rate of experiments performed using the tapered squeeze ring of fig. 10.

Fig. 25 shows a success rate graph of an experiment performed using the hard ring type pressing ring of fig. 11.

Detailed Description

For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. Any alterations and further modifications in the described embodiments, and any further applications of the principles of the invention as described herein are contemplated as would normally occur to one skilled in the art to which the invention relates.

As discussed in detail above, one goal of the diagnostic industry is to develop commercially available integrated test devices. The term "integrated device" has been commonly used in the industry to refer to a device that automatically performs the various steps required to test a bodily fluid (e.g., blood, interstitial fluid, etc.). These steps in an integrated device typically include: the skin is penetrated or otherwise stimulated with a sample of bodily fluid drawn from the skin, and the sample is tested and selectively expressed from the incision or otherwise facilitated with the production of bodily fluid. Although integrated devices have been commercially marketed, such asSOF-TACT^TMBrand diabetes management systems, but these integrated devices currently fail to market due to several factors including the bulkiness of the device and the low test rates. As previously mentioned, testing reliability or success for a setThe ready equipment is of great importance because: due to the automation of integrated devices, it is difficult to correct test errors halfway through the test.

Integrated disposable devices have been proposed, namely: the various components in contact with the bodily fluids are discarded after each test and replaced with new ones to avoid cross-contamination problems. These integrated disposable devices generally allow for analysis and collection of smaller sample sizes, thereby increasing the flexibility of collecting body fluids from the body and reducing pain in collecting body fluids. In the industry, the term "integrated disposable device" generally refers to a relatively small and inexpensive device that performs most or all of the testing steps, such as piercing the skin, drawing a sample, and at least partially analyzing the sample. Integrated disposable devices typically combine several types of piercing means, such as lancets or needles, with test or analytical means, such as test strips and/or reagents, for analyzing a sample. The test tools on integrated disposable devices typically include electrodes, enzymes, reagents, media, etc. for analyzing body fluids. The meter loaded with the integrated disposable includes electronics, displays, etc. that, together with the integrated disposable's test tool, facilitate analysis of the sample using any of a variety of analytical techniques, some of which are listed as electrochemical and/or photometric techniques, for example. Typically, the meter contains relatively expensive components, while the integrated disposable device contains relatively inexpensive components that can be discarded after each use. In most cases, the test tool is fixed to the piercing tool in some way, but there are some integrated disposable device designs in which the piercing tool and the test tool are only associated together for a short period of time during the test.

The integrated disposable devices may be further subdivided into specific design classes. Some of the more common integrated disposable device types include lancet integrated test elements (or simply "LITs") and "microsamplers". A LIT is generally considered to be an integrated disposable device that secures a test strip and a lancet in a fixed or movable manner. The LIT typically collects body fluids from the epidermal surface in a manner similar to that of a blood-sucking bat. On the other hand, microsamplers generally collect most of the body fluids under the epidermis in a manner similar to mosquitoes. The term "microsampler" generally refers to an integrated disposable device having a puncturing unit that is functionally similar to a needle attached or otherwise associated with a test tool. The lancing unit in the microsampler has a capillary channel that draws body fluid from beneath the epidermis to the test tool. The capillary channel in the micro-sampler may be of closed design, open design or a combination of both. In a closed capillary channel design, the capillary channel is open to the environment at only one end of the tip portion, and is therefore capable of collecting body fluid. On the other hand, in an open capillary design, the entire length of the capillary channel is open to the environment and is therefore able to collect body fluids. The open capillary channel design can simplify manufacturing and improve body fluid collection because: bodily fluids can be collected along the entire length and even on the surface of the epidermis. However, the inventors have found that one problem with such open capillary channels is that in some cases the test results may be affected. Specifically, given that microsamplers typically collect body fluid in the sub-microliter region (less than 1 μ l), in some cases from 20nl to 200nl, the inventors found that: evaporation (although very little) along the open capillary channel changes the concentration level and therefore adversely affects the test results. It has been found that the open capillary channels create a relatively large surface area for the sample, which promotes evaporation. The inventors have found that drawing the sample and quickly placing the sample on the test tool greatly reduces the effects of evaporation. In particular, the inventors found that placing the sample to the test tool within 500ms from the beginning of the penetration into the skin reduced evaporation. The problem is how to make such a rapid placement of the body fluid possible. However, it has also been found that it is feasible to place the body fluid even within 150ms or 200ms, and that evaporation can be further reduced, with further benefits from placement within 100ms or even 75 ms.

As noted above, one of the major obstacles to commercially successful integrated devices is the ability to reliably collect a sample of bodily fluid on a consistent basis. With conventional non-integrated methods, the user can intervene in the collection process to ensure that a successful test can be performed. Integrated devices, and particularly integrated disposable devices, automatically perform the body fluid collection steps and therefore the steps are generally not repeated to ensure success. High success rates of body fluid collection are one of the major factors in determining whether an integrated device is commercially viable. To determine the collection success rate, a test is considered successful when a body fluid sample of sufficient volume is collected to enable the test tool to accurately analyze the body fluid sample. The sufficient volume for the test device depends on the test technique used. Currently, most existing test strips, such as photometric and electrochemical test strips, are capable of adequately analyzing a body fluid sample having a volume of less than 1 μ l in 10 seconds or less, even 5 seconds. However, the sample volume may be too small to achieve accurate test results. In other words, today's testing techniques have limitations on the minimum body fluid volume required for accurate body fluid analysis. Current commercial products are capable of accurately testing a minimum of 200 to 300nl of bodily fluid. This accurate test minimum volume can be reduced to 20nl using current techniques/chemistry, however, any sample volume less than 20nl cannot currently produce accurate test results on a consistent basis. It is considered that the minimum requirement for the success rate of body fluid collection of a commercially acceptable integrated device needs to be at least around 80%. In practice, for a commercially successful integrated device, the success rate should be 95% or above 95%. To date, the inventors have not found that any commercial integrated disposable or other integrated device is capable of achieving these high fluid collection success rates under practical conditions.

The inventors have found that a major factor that is detrimental to the success of body fluid testing in practice is the reflex action that occurs due to the pain experienced during penetration into the epidermis. The following are found: the problem of collecting body fluids using an integrated device is addressed by piercing the epidermis, collecting body fluids from the epidermis, and removing the piercing member from the epidermis before a reflex action occurs to achieve a commercially acceptable collection success rate. In the worst case, depending on the individual, the reflex action may occur within about 200ms from the initial penetration into the epidermis. Thus, the inventors found that: it is desirable to remove the penetrating member from the incision within about 200ms of the initial penetration of the skin, and in particular within about 150 ms. Furthermore, successful testing is achieved within 100ms or even 75ms of the initial penetration of the penetrating member, which provides a further safety buffer.

The initial idea was to collect only a few nanoliters of body fluid volume in a rapid manner, but in reality the collected sample volume was too small for accurate testing. As mentioned above, successful fluid collection is only considered when the volume of fluid collected is sufficient for accurate testing, which in the prior art is from a theoretical 20nl under ideal conditions to a minimum of 200nl under actual testing conditions. One of the many unexpected findings is that not all bodily fluids need be within the capillary channel when the penetrating member is removed from the epidermis. Instead, when withdrawn from the epidermis, the bodily fluid may adhere to the piercing member outside the capillary channel and be later drawn into the capillary channel. In this case, a piercing element with an open capillary channel design is advantageous because: bodily fluid can be drawn along the entire length of the capillary channel.

To achieve a high fluid collection success rate of an integrated device in a short time, the inventors have found that three general factors generally contribute to successful fluid collection: the amount of force applied against the epidermis; a tip design of the piercing member; and a piercing profile. Furthermore, the inventors have found that none of the above factors alone results in a consistent and rapid collection of body fluid. Rather, specific combinations and levels of these factors are required. In particular, in order to achieve successful fluid collection within a short period of time (i.e. prior to reflex action) on a commercially acceptable basis, it was found that: a force of at least 6N should be applied to the epidermis to express body fluid, the inlet of the capillary channel should be recessed from the tip 350 to 600 μm, and the time of the withdrawal (exit) process should be longer than the time of the penetration (entry) process.

Fig. 1 illustrates an integrated device or system 30 according to one embodiment for achieving rapid sample collection and/or placement. As can be seen, the system 30 comprises: a meter 40, the meter 40 having a display 50 for providing analysis results and other information; at least one button 60 for controlling and inputting data into the meter; and a firing mechanism 70. The gauge 40 also incorporates a pressure sensitive trigger 80, the pressure sensitive trigger 80 activating the firing mechanism 70 when the gauge is pressed against the epidermis with a predetermined force. An example of one such gauge and pressure sensitive trigger is described in U.S. patent No. 6,319,210 issued to Douglas et al, which is incorporated herein by reference in its entirety. The pressure sensitive trigger may also be constructed in other ways. For example, the pressure sensitive trigger 80 may be mechanical in nature, electronic in nature, or a combination of both. In one variation, the trigger 80 releases a safety that allows the operator to manually fire the firing mechanism 70, and in another embodiment, the display 50 provides an indicator that the firing mechanism 70 may be fired when a predetermined force is applied. The system 30 also integrates: a squeezing or body fluid pressurizing member 90 for pressurizing body fluid beneath the epidermis; and an integrated disposable device 100 for piercing the epidermis and analyzing the body fluid sample. The integrated disposable devices 100 may be loaded and/or unloaded, and the integrated disposable devices 100 may be arranged in individual units or in groups, e.g., in cassettes, drums, wheels, boxes, and the like. It should be appreciated that the meter system 30 may include more or fewer components and/or be configured differently in other embodiments.

In the illustrated embodiment, the integrated disposable device 100 is a micro-sampler, but it should be understood that certain features may be suitable for use in other types of integrated disposable devices and integrated devices. An example of a micro-sampler 100 for performing rapid fluid collection will be described initially with reference to fig. 2, 3 and 4. It will be appreciated that other types of integrated disposable devices may be modified to include the features of the micro-sampler 100 shown. Similar to other types of integrated disposable devices, the microsampler 100 of fig. 2 is typically a single use device configured to form an incision, draw a bodily fluid sample, and analyze the collected bodily fluid sample. The micro-sampler 100 is loaded individually or collectively (e.g., in a cartridge) into the gauge 40 or piercing device, and the micro-sampler 100 is then shot into the epidermis by the firing mechanism 70. When loaded individually, the micro-sampler 100 is typically unloaded from the meter and discarded after each test to minimize the risk of cross-infection. When loaded in a cassette, box, drum, etc., the entire cassette is unloaded or properly processed after all or most of the micro-samplers 100 have been used. For an example of a micro-sampler cartridge design, please refer to U.S. patent application No. 11/549,302, filed 2006, 10, 13, which is incorporated herein by reference.

Fig. 2 shows a top view of the micro-sampler 100. As can be seen, the micro-sampler 100 includes a body portion 102, a shank or shaft portion 104 extending from the body portion 102, and a tip portion 106 at the end of the shaft 104 that is sharpened for cutting. The body 102 has a firing mechanism engagement opening 108 wherein the firing mechanism 70 of the gauge 40 retains the micro-sampler 100 during penetration of the epidermis or other tissue. It should be understood that the micro-sampler 100 may be otherwise secured to the firing mechanism 70, or that the micro-sampler 100 may not even be mechanically coupled to the firing mechanism, but may be fired indirectly, for example, through the use of electromagnetic forces. The body 102 also has a sample analysis chamber or chamber 110 in which a bodily fluid sample is collected and analyzed by a testing device or analysis tool 111. The test device 111 in the micro-sampler 100 may contain chemicals such as reagents, enzymes, media, and other associated components such as electrodes to analyze the bodily fluid sample. In another form, the analysis chamber 110 may also serve as a collection point for placement on a separate test strip for analytical purposes. Alternatively, the bodily fluid sample may be analyzed by any type of analytical technique, such as by electrochemical (e.g., amperometric, coulometric, etc.) and/or photometric analytical techniques, to name but a few. The body fluid can be analyzed rapidly in less than 10 seconds or even in 0.1-6 seconds. Examples of such rapid analysis techniques are described in U.S. patent No. 7,276,146B2, which is incorporated herein by reference. With continued reference to fig. 2, a capillary channel 112 configured to move a liquid sample by capillary action extends along the shaft 104 from the tip 106 to an analysis chamber 110 proximate the testing device. While the micro-sampler 100 may be made using a variety of materials, such as metal, ceramic, and/or plastic, in one embodiment the micro-sampler 100 is made of surgical grade stainless steel. Typically, surgical grade stainless steel is hydrophobic, and when hydrophobic, the capillary channel 112, along with the sample analysis chamber 110, may be treated and/or made hydrophilic in whole or in part to promote capillary action.

As described above, it has been found that the size and configuration of the micro-sampler 100, particularly near the tip 106, reduces pain and increases fluid collection by significantly increasing the collection success rate over a relatively short period of time (before reflex action occurs). FIG. 3 shows an enlarged top view of the shaft 104 near the tip 106 of the micro-sampler 100, and FIG. 4 depicts a side view of the shaft 104 near the tip 106. As can be seen, the micro-sampler 100 has two sharp cutting edges 114, the cutting edges 114 intersecting at the tip 106 to form an included or edge angle 116. In one form, the edge angle 116 is from 20 to 40, and in one particular form, the edge angle 116 is about 30. Away from the tip 106, the cutting edge 114 transitions into opposite parallel sides 118 of the shaft 104. At side 118, shaft 104 has a width 120 of 300 to 700 μm, and in one particular form, about 300 μm. In one embodiment, the micro-sampler 100 also has a thickness 119 of 50 to 150 μm, and in one particular form, has a thickness 119 of about 127 μm.

Referring to fig. 3 and 4, the side 118 of the shaft 104 has a sidewall 122, the sidewall 122 defining the capillary passage 112. The capillary channel 112 along the sidewall 122 is treated, coated and/or otherwise made hydrophilic to enhance the drawing of body fluid by capillary action. Capillary channel 112 is sized and configured to draw body fluid from the incision site to analysis chamber 110 by capillary action. When the capillary channel 112 is open, bodily fluid may be collected along the entire length of the capillary channel 112. This is in sharp contrast to conventional (closed) hypodermic needles that withdraw body fluid through a single opening. Because the capillaries (or blood vessels) under the incised epidermis are randomly distributed, the distribution of blood or other bodily fluids within the incision may not be uniform. In other words, there is an area along the incision where more body fluid can be supplied than elsewhere. When the capillary channel 112 is open, a significant amount of blood may be wiped or otherwise drawn into the capillary channel 112 from a high supply area along the length of the capillary channel 112 during withdrawal of the microsampler 100.

In the illustrated embodiment, the sidewall 122 does not extend completely to the tip 106, but rather, an open portion 124 is formed between an opening 126 (defined by an end 128 of the sidewall 122) of the capillary channel 112 and the tip 106 of the microsampler 100. Between the end of the side wall 122 and the tip 106, the micro-sampler 100 has an angled wall portion 130 at the open portion 124, the angled wall portion 130 extending at an angle 132 relative to a bottom side 134 of the micro-sampler 100, as shown in fig. 4. In one form, the angle 132 of the angled wall portion is about 35 °. It should be noted that the side wall 122 along the capillary passage 112 is generally of sufficient height to draw body fluid by capillary action; while the angled wall portion 130 along the open portion 124 generally provides insufficient contact area for drawing body fluid by capillary action. The end 128 of the sidewall 122 defines the opening 126 of the capillary passage 112 and the portion of the sidewall 122 between the end 128 and the tip 106 is considered to be the open portion 124. Alternatively or additionally, in another embodiment, the open portion 124 is hydrophobic or otherwise made to inhibit capillary action along the open portion 124. In one form, the open portion 124 has a length 136 of 350 to 600 μm, the length 136 being defined as the distance from the tip 106 to the capillary channel opening 126 (or end 128), and in one particular embodiment, the channel opening 126 is located about 425 μm from the tip 106. As described below, it has been unexpectedly found that the length 136 of the open portion 124 significantly reduces the time required for successful collection of a body fluid sample.

As previously described, capillary channel 112 is hydrophilic and is sized to draw a body fluid sample from the incision site to analysis chamber 110 by capillary action. In general, capillary action is based on the surface tension of the liquid (sample) being drawn and the adhesion between the sample and the capillary channel. In particular, the attachment of the sample to the walls of the capillary channel 112 causes the edge of the sample to move forward, forming a convex meniscus. The surface tension of the sample keeps the surface intact, so the entire sample surface moves further into the capillary channel 112, in addition to only the edge movement. It will be appreciated that the overall contact between the meniscus of the sample and the walls of the channel is one of the factors controlling the adhesion between the sample and the walls, and thus determining whether or not capillary action occurs and the degree and speed of capillary flow. In the case of an open capillary channel, one of the two sides that normally create adhesion in a closed capillary design is removed, thereby reducing the overall adhesion between the sample and the wall. The walls of capillary channel 112 in the micro-sampler are designed to compensate for this effect so that rapid capillary action can occur. Fig. 5 shows a cross-sectional view of capillary passage 112 taken along line 5-5 in fig. 4. Capillary channel 112 has a depth 138 and a width 140. In one embodiment, the depth 138 is about 0.501mm and the width is about 0.358 mm. The aspect ratio of capillary passage 112 is depth 138 divided by width 140. In one form, capillary channel 112 is hydrophilic and has an aspect ratio (depth 138/width 140) of between 0.7 and 1.6, and in one particular form, capillary channel 112 has an aspect ratio of about 1.4. It has been found that the above aspect ratio in an open capillary design promotes rapid fluid collection of a body fluid sample having a similar viscosity as blood.

FIG. 6 shows a micro-sampler 142 that has several features in common with the micro-sampler 100 of FIG. 2, such as the body, the shaft 104, the tip 106, and the capillary channel 112. The various dimensions and features of the micro-sampler 142 of fig. 6 are the same as those described with reference to fig. 3 and 4. However, the overall shape of the analysis chamber 110 and the body 102 is different from that described above. In particular, the analysis chamber 110 in fig. 6 is in an open form allowing bodily fluids to pool on the test element 111. In addition, the micro-sampler 142 in FIG. 6 has two firing mechanism engagement openings 108 instead of one to provide better firing stability.

To reduce the body fluid collection time to enable collection of body fluid before reflex action occurs, body fluid expression is used to increase the rate of drainage from the incision by applying pressure to the body fluid around the incision site. During their research, the inventors studied the effect of various types of the pressing member 90 on the success rate of rapid body fluid collection. The findings of the inventors' studies on various pressing members will be discussed in detail below. Figures 7, 8, 9, 10, and 11 illustrate various other examples of a compression member 90 for use in conjunction with the system 30 of figure 1 for applying pressure to a bodily fluid beneath the skin.

Fig. 7 illustrates an example of a expression assembly 144, the expression assembly 144 including a micro-sampler 100 and an expression unit or member 146 for expressing a bodily fluid. The expression unit 146 has a winding design such that the expression unit 146 is wound around a body part, such as a finger, during expression of bodily fluid. It can be seen that the compression unit has a sleeve 148 extending around a body part receiving cavity 150. An incision site opening 152 is defined in the body 148 to allow the micro-sampler 100 or other incision forming tool, such as a lancet or needle, to form an incision. In one form, the internal diameter of the cut-out location opening 152 is 4.0mm to 7.0 mm. Within the chamber 150, the pressing unit 146 has a tapered portion 154 surrounding the cut-out location opening 152. Around the tapered portion 154, the expression unit 146 has a spacer ring 156, the spacer ring 156 promoting fluid confinement around the incision site. In the illustrated embodiment, the spacer rings are saddle shaped and protrude from the inner surface of the pressing unit 146.

Fig. 8 depicts an O-ring type extruded member or ring 160 that uses an O-ring having a medium hard material hardness. An example of such an O-ring compression ring is described in U.S. patent application No. 11/466,202 filed on 26.8.2006, which is incorporated by reference in its entirety. Fig. 9 shows a negative S-shaped extrusion ring or member 162 having a hard material hardness. For further description of the overall shape of the negative S-shaped squeeze ring 162, please refer to U.S. patent publication No. 2005/0215923a1, published on 9/29/2005, which is incorporated by reference in its entirety. Fig. 10 shows a "cone" or flexible cone-type pressing member or ring 164, which is made of a flexible or soft material (35shore a). Fig. 11 shows a brass extrusion ring 166 that is overmolded with rubber, so that the extrusion ring 166 is generally hard. It should be understood that the hard squeeze ring 166 in fig. 11 may be made of other hard materials such as steel, iron, etc., as well as covered with other types of resilient materials such as various plastics. The pressing member 90 in fig. 8, 9, 10 and 11 all have an inner diameter of 5.5 mm. The outer diameters of the O-ring 160 in fig. 8, the negative S-ring 162 in fig. 9, the tapered extrusion ring 164 in fig. 10, and the hard extrusion ring 166 in fig. 11 are 9.8mm, 10.0mm, 10.7mm, and 8.3mm, respectively.

To aid in understanding and appreciation, the overall technique for rapid collection of a bodily fluid sample will first be described with reference to fig. 12-18, followed by a detailed discussion of the specific changes required to achieve a commercially successful bodily fluid collection before a reflex action occurs. Fig. 12-18 show enlarged perspective views of the micro-sampler 100 during various stages of body fluid collection. The technique of collecting body fluid will be described with reference to collecting body fluid from finger 168, but it should be understood that body fluid may also be collected from other body parts. Further, the technique will be described with reference to the micro-sampler 100 of FIG. 2, but other types of integrated devices or integrated disposable devices may also be used in the technique. Before the incision is made, the pressing member 90 is pressed against the finger, as shown in fig. 12. The expression member 90 is pressed against the desired incision site 170 on the finger 168 with sufficient force so that the expression member 90 defines the perimeter of the isolation zone to limit blood (and/or cellular fluid) loss from the incision site 170 during cutting. The peripheral force is applied by the expression member 90 for a brief period of time to create an isolated fluid filled area of the skin. Referring to fig. 13, the shot mechanism 70 fires the micro-sampler 100 such that the tip 106 extends through the opening of the pressing member 90 to cut the skin 168 to a depth sufficient to sever one or more capillaries in a relatively short period of time. In one form, the micro-sampler 100 is fired at a speed greater than or equal to 1.2m/s, preferably 1.5 m/s. The micro-sampler 100 reaches a maximum penetration depth within 5ms or within 5ms, preferably within 3ms or within 3 ms. This rapid cutting was found to minimize pain.

While some body fluid may be collected in capillary passage 112 during initial penetration, most of the body fluid is collected after the maximum penetration depth is reached. When the maximum penetration depth is reached, the tip 106 of the micro-sampler 100 may remain or stay at the maximum depth or partially withdrawn but still remain below the surface of the epidermis 168. The inventors have discovered that leaving at least a portion of the open capillary channel 112 in the epidermis for longer than the initial penetration of the microsampler 100 significantly improves rapid fluid collection. During this dwell time, the micro-sampler 10 may remain stationary or in the process of being withdrawn from the epidermis 168.

Body fluid collection can be performed in several ways depending on the integrated disposable device used. For example, body fluid collection may be performed under the epidermis 168 like a mosquito, on the epidermis like a blood-sucking bat, or using a combination of both techniques. For example, the micro-sampler 100 described previously is capable of collecting body fluids beneath and/or on the epidermal surface, but in selected embodiments the micro-sampler 100 generally collects a majority of body fluids beneath the epidermis like a mosquito. The capillary channel 112 in the micro-sampler 100 is open along its length such that: the open capillary channels 112 can extend over the surface of the epidermis to collect blood (or other bodily fluids) pooling on the surface of the epidermis while simultaneously drawing blood beneath the epidermis through capillary action. It is desirable that the sample size be small enough for analytical purposes, as a smaller sample size allows for a shallower penetration depth, which in turn reduces the pain experienced during cutting. Furthermore, a smaller sample size generally allows for faster analysis times, a feature that is desirable to consumers.

Fig. 14 shows drawing of body fluid 172 along the capillary channel 112 while the tip 106 remains under the epidermis 168. Reference numeral 174 shows the leading edge or meniscus of the body fluid 172 drawn along the capillary channel 112. As explained in more detail below, a portion of the body fluid 172 may remain attached to the micro-sampler 100 outside of the capillary channel 112 at a location where the body fluid may later be drawn into the capillary channel 112. One or more drops 176 of the body fluid 172 may form on the micro-sampler 100 and/or on the epidermis 168 along the capillary channel 112. As can be seen in FIG. 15, a single drop 176 forms on the skin 168 along the axis 104 of the microsampler 100 as the tip 106 is nearly removed from the skin. Specifically, a droplet 176 is formed near the capillary channel opening 126. The drops 176 may also form elsewhere. Referring to FIG. 16, a second drop 178 of body fluid 172 (or sometimes even a bubble) forms on the micro-sampler 100 at the transition between the body 102 and the shaft 104. To facilitate droplet formation, portions of the micro-sampler 100, such as the shaft 104 and/or along the capillary channel 112, may be treated or otherwise made hydrophilic. Other areas of the microsampler 100, such as areas where the body fluid 172 is not drawn into the capillary channel 112 and/or at the open portion 124, may be treated or otherwise made hydrophobic to inhibit droplet formation at selected areas.

As mentioned above, the particular size of the open section 124 on the micro-sampler 100 has been unexpectedly found to be a factor in promoting rapid fluid collection. Although not an absolute determination, it is believed that the open portion 124 may function to hold a drop 176 of the body fluid 172 at the capillary channel inlet 126 on the microsampler 100 so that the body fluid 172 may be subsequently drawn into the capillary channel 112 after the microsampler 100 is withdrawn from the epidermis. Referring to fig. 16, the droplet 176 at the capillary channel inlet 126 is separated from the droplet 180 on the skin at the open portion 124. In theory, the open portion 124 allows the droplets 176 on the micro-sampler 100 to separate from the droplets 180 on the skin 168 without the droplets 180 on the skin 168 pulling body fluid from the droplets 176 on the micro-sampler 100, as shown in FIGS. 16 and 17. The micro-sampler 100 is typically completely withdrawn from the epidermis 168 within a reflex response time, which is about 100 to 200ms, depending on the individual. When the tip 106 is withdrawn from the skin 168, the droplet 176 remains on the microsampler 100 around the capillary channel inlet 126. The force exerted by the pressing member 90 may be relaxed before the micro-sampler 100 is withdrawn from the epidermis 168, while it is being withdrawn from the epidermis 168, or after it is being withdrawn from the epidermis 168.

The droplets 176, 178 on the micro-sampler 100 essentially form a reservoir on the micro-sampler 100, allowing the filling of the capillary channel 112 to continue even after the tip 106 of the micro-sampler 100 is withdrawn from the skin 168. The ability to fill the capillary channel 112 after withdrawal promotes successful fluid collection even when the micro-sampler 100 penetrates the epidermis 168 and withdraws within a short period of time, such as before a reflex action occurs. Fig. 17 and 18 show how drops 176 and 178 of body fluid 172 on the micro-sampler 100 complete the filling of the capillary channel 112. As seen by the leading edge 174 of body fluid 172 in FIG. 17, the body fluid 172 has not completely filled the capillary passage 112, but the drop 176 (and drop 178) provides a reservoir of body fluid 172 that can be drawn into the capillary. Fig. 18 shows that body fluid 172, once formed into a droplet 176 at capillary channel inlet 126, fills capillary channel 112 such that leading edge 174 of body fluid 172 is located at the end of capillary channel 112.

In all of the figures discussed above (fig. 12-18), the testing device 111 is not shown so that the body fluid 172 filling the capillary channel 112 can be easily viewed. It should be appreciated that when the capillary is partially or fully filled, the body fluid 172 begins to be placed onto the testing device 111. In one embodiment, the capillary channel 112 has a volume equal to or greater than the volume required for an accurate test, and the micro-sampler 100 is configured to deposit body fluid to the test device 111 only after the capillary channel 112 is filled with body fluid 172.

As described above, the inventors have discovered that evaporation of the sample during collection and analysis of the body fluid is one cause of inaccuracy in the results of sample testing in the sub-microliter or nanoliter range. In these small test volumes, even small changes in volume can cause significant differences in analyte concentration measurements. It should be appreciated that the capillary channel 112 in the micro-sampler 100 has an open design that is susceptible to evaporation. The problem of evaporation of such open capillary channels is solved by: the sample is taken within 500ms of penetrating the skin and placed on the sample analysis device 111. In other aspects, placement of body fluid within 150ms or 200ms to further reduce evaporation, and in other aspects, placement of body fluid within 100ms or even within 75ms provides further benefits. By placing the collected body fluid in this rapid manner, only a small amount of evaporation occurs, resulting in more accurate results. The time is measured from the initial penetration of the micro-sampler 100 into the epidermis 168. In one embodiment, the measurement of these times is stopped once a sufficient amount of body fluid for testing purposes has been placed on the testing device 111. The end time may be measured by using a drop detector or the like within the micro-sampler 100. It should be understood that quick placement may be measured or based on other time periods. For example, the placement time may be based on how long the sample is exposed to air before being placed in the test tool and/or inhaled into the test tool.

One of the previously mentioned factors in achieving successful fluid collection before the reflex action occurs is the piercing or piercing profile used to extend and retract the micro-sampler 100 during the formation of the cut. The following are found: the profile should include a relatively fast penetration or extension phase followed by a relatively long withdrawal phase of the micro-sampler 100 from the epidermis. A rapid penetration process is believed to reduce pain and increase the time available for the withdrawal process, while a longer withdrawal increases the sub-epidermal residence time of the capillary passage 112, which is believed to increase the amount of body fluid collected.

FIG. 19 shows a graph 190, the graph 190 showing a penetration profile for the micro-sampler 100 according to one technique for sampling bodily fluids in a rapid manner. The X-axis 192 in the graph 190 represents time and the Y-axis 194 represents the distance traveled by the tip 106 of the micro-sampler 100. Contour 196 shows the penetration profile of micro-sampler 100 and dashed line 198 represents the epidermal surface. It can be seen that the micro-sampler 100 is launched and that the micro-sampler 100 reaches its maximum penetration depth within 3 milliseconds (ms). Once the maximum penetration depth of the tip 106, in this example about 1.6 to 1.7mm, is achieved, the micro-sampler 100 begins to withdraw at a generally constant rate. In other words, in this example, the tip 106 of the microsampler 100 does not reside or reside at the maximum penetration depth before being withdrawn from the skin. In the illustrated case, the tip 106 is withdrawn at a generally continuous rate of about 497ms before being withdrawn from the epidermis, with a total residence time within the epidermis of about 500 ms. As the tip 106 of the microsampler 100 is withdrawn within the epidermis, the microsampler 100 collects bodily fluids, and even once removed from the epidermis, the microsampler 100 is able to collect bodily fluids from the epidermal surface for at least a short distance.

Fig. 20 shows a graph 200, the graph 200 showing a piercing profile for the micro-sampler 100 according to another technique for rapid sampling of bodily fluids. Contour 206 shows the penetration profile of micro-sampler 100 and dashed line 198 represents the epidermal surface. It can be seen that the tip 106 of the micro-sampler 100 reaches a maximum penetration depth of about 1.6 to 1.7mm and is withdrawn to a depth of about 0.8mm within 3 ms. In theory, partial withdrawal of the tip 106 promotes pooling of body fluid within the incision, which in turn can be collected by the capillary channel 112. The tip 106 of the micro-sampler 100 stays at a depth of 0.8mm for about 477ms to collect body fluid, and then the tip 106 of the micro-sampler 100 quickly exits from the epidermis in about 5 ms. In this example, the total residence time of the micro-sampler 100 within the epidermis is approximately 485 ms. It is contemplated that the rapid lancing, partial withdrawal, long dwell, and rapid total withdrawal steps of the technique shown in fig. 20 promote successful rapid body fluid collection. It should be understood that in other examples, the specific time may vary.

In one experiment, 20 subjects involved 140 punctures per micro-sampler design were evaluated for success rate of filling the micro-sampler. 3 types of micro-sampler designs were used: design A, design B, and design C. In actual experiments, microsampler designs A, B and C were referred to as microsampler designs "87", "88", and "89", respectively. The micro-sampler designs A, B and C are similar to the micro-sampler 100 shown in FIGS. 2, 3, 4, and 5. However, in these designs (see fig. 3), the length 136 of the open portion 124 defined by the distance from the tip 106 to the capillary channel opening 126 is different. Specifically, the length 136 of the open section 124 is 382 μm, 425 μm, and 573 μm for the micro-sampler designs A, B and C, respectively. In the experiment, capillary channels 112 of lengths 4.5mm and 8.6mm were tested. Filling is considered successful when the entire length of the capillary channel 112 is filled with body fluid, in this case, blood. It will be appreciated that if substantially the entire length of the capillary channel 112 is not filled, blood will not be able to be placed into the analysis device 111.

All objects were pierced to the same depth of 1.6 mm. In an experiment, the expression assembly 144 (or sometimes referred to as a "cone") applied a force of 10N to a subject's finger for bodily fluid expression purposes. A force is applied to the finger using the squeezing unit 146 prior to forming the incision to pressurize the bodily fluid within the epidermis. This force is continuously applied as the incision is cut and during sample collection. The previously described graph 190 in fig. 19 shows an example of a puncture profile used in this experiment. The piercing portion of the profile is relatively fast and constant and the withdrawal of the micro-sampler 100 is a relatively slow, continuous, single-stage step. In one example, the velocity of the micro-sampler 100 at initial contact is greater than or equal to 1.3m/s and the tip 106 of the micro-sampler 100 reaches a maximum penetration depth of 1.6mm within 3-5 ms. The withdrawal time varies from 25 milliseconds to 500 milliseconds. In all examples of the experiment, complete withdrawal of the microsampler 100 from the epidermis occurred in less than 1000 ms. Table 1 below shows the success rate of filling 4.5mm and 8.6mm long capillary channels 112 using the micro-sampler design A, B and C. Diagram 210 in fig. 21 shows an expanded view of the same data for a design having a 4.5mm long capillary channel 112. It should be noted that: the "channel filling time" in diagram 210 of fig. 21 is the same as the "pullback time" indicated in table 1 below. It should also be noted that: the withdrawal time is based on the total time elapsed from that point so that it includes the time required to reach the maximum penetration depth plus the time required for the microsampler 100 to withdraw from the epidermis. For example, the 500ms withdrawal time in Table 1 below includes 3ms required to reach the maximum penetration depth and 497ms required for the microsampler 100 to be withdrawn from the epidermis.

TABLE 1

It has been unexpectedly found that the length 136 of the open portion 124 significantly improves the success rate at relatively short body fluid collection times. As can be seen in fig. 21, for a 4.5mm long capillary channel, capillary filling with a success rate of 100% (N-140 times) was achieved using micro-sampler design B (open portion 124 having a length 136 of 425 μm) with a puncture profile with a withdrawal time of 200ms with a force of 10N applied by the squeezing unit 146 on the finger. The micro-sampler B design achieves a 100% fill success rate in a relatively short period of time when compared to other designs. The only variable that controls the success of the overall test is the reliability of the test strip (or other test tool) used to analyze the bodily fluid sample for both the incision formation and sample collection steps to achieve 100% channel fill. The significance of this 100% sample collection success rate lies in: the overall success rate of the micro-sampler will be comparable to or even the same as current (even future) test strips.

Using this integrated design so that all steps are performed quickly, all test success rates are predicted because few manual operations by the user can be better than with conventional designs. With conventional (non-integrated) test strips, the amount of body fluid sample is limited to some extent by hand-eye coordination and motor skills of the user. If the drop of blood is too small, the user will not be able to accurately place the test strip to collect a blood or other bodily fluid sample. With the advent of test strip technology that allows for smaller sample volumes, this limiting factor will become the ability of the user to collect the sample. It should be appreciated that a smaller sample size can be obtained at a shallower penetration depth, thus providing a user with less pain. Also, the speed at which the sample is collected and analyzed will be limited by the ability of the user to collect the sample and load the test strip into the meter. The faster the test is completed, the more convenient it is for the user, as the user can spend less time performing the test.

Differences in skin properties, such as skin elasticity, can alter the actual penetration depth into the epidermis. For example, the firing mechanism 79 is set to 1.6mm, but the actual penetration depth may be 1.2 mm. In this regard, a second study was conducted on both individuals to compensate for skin differences. In other words, the epidermal penetration depth is accurately controlled or calibrated for the individual. In this experiment, the depth of penetration was initially 1.6 mm. Penetrate the target and collect the bodily fluid. A squeezing unit 146 of the type described above is used to apply a force of 4N to 10N on the skin of the finger before the skin is pierced and until the sample is collected. The puncture profile shown in graph 190 in fig. 19 was used during the experiment (i.e., rapid maximum depth reached and relatively slow continuous withdrawal from the epidermis). If 300nl of fluid is collected, the setting of the firing mechanism will be reduced by half and the fluid collection process repeated until a minimum depth is reached at which 300nl can be collected consistently.

The minimum or calibrated depth setting is then used to collect body fluid from each subject. Tables 2 and 3 below show the success rate of filling 8.6mm channels in this experiment using micro-sampler design a and B, respectively.

TABLE 2

TABLE 3

As can be seen in tables 2 and 3, using both microsampler designs a and B achieves 100% success rate for 8.6mm channel fill (or less) with a compression force of at least 10N and withdrawal time of 75 ms. At a withdrawal time of 75ms, fluid collection may be performed prior to the reflex action of the individual. Microsampler design B improved fluid collection success at other withdrawal times compared to design a.

Further experiments were conducted to determine the minimum force exerted by squeezing against the epidermis while still achieving successful rapid fluid collection. The compression unit 90 shown in fig. 8, 9, 10 and 11 was tested at different force levels for the micro-sampler design B. In particular, each pressing unit 90 applies 4.0N, 6.0N and 8.0N to the skins. Further, at three different times: 75ms, 500m and 1000ms, the total residence time of the microsampler 100 under the skin (from initial penetration to complete exit) was tested. The puncture profile 196 of the graph in fig. 19 was used during bodily fluid collection. In each test, capillary channel filling was considered successful when at least 4.5mm of the length of capillary channel 112 was filled. The graph 220 in fig. 22 shows the test results of the O-ring type pressing member 160 shown in fig. 8. In fig. 23, a graph 230 depicts the test results of the negative S-shaped compression member 162 of fig. 9. The graph 240 in fig. 24 shows the test results of the tapered pressing member 164 of fig. 10, and the graph 250 in fig. 25 shows the test results of the hard pressing member 166 of fig. 11. From these results, it should be appreciated that when a 8.0N compression force or pressure is applied to the epidermis using any of the compression units 90 tested, the micro-sampler 100 can be successfully collected when withdrawn within 75ms of the initial penetration before the reflex action occurs. At a force level of 6.0N, a commercially acceptable sample collection success rate was achieved at 75ms for the conical compression unit 164 and the hard compression unit 166.

While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes, equivalents, and modifications that come within the spirit of the invention as defined by the following claims are desired to be protected.

Claims (8)

1. A blood pressing and sampling device, comprising:

a pressing unit for pressing the epidermis;

a skin penetrating member for penetrating the skin, the skin penetrating member including a liquid collection structure for collecting bodily fluids after the penetrating the skin, and the skin penetrating member comprising: a micro-sampler having an open capillary channel for drawing liquid from the epidermis;

and means for removing the skin penetrating member from the skin;

and collecting the bodily fluid and removing the skin penetrating member prior to a reflecting action occurring as a result of the penetrating skin, wherein the skin penetrating member has a tip with an open portion having a length of at least 350 μm and at most 600 μm.

2. A blood pressing and sampling device, comprising:

a pressing unit for pressing the epidermis;

a skin penetrating member for penetrating the skin, the skin penetrating member including a fluid collection structure for collecting bodily fluids after the penetration of the skin;

and means for removing the skin penetrating member from the skin;

and collecting the bodily fluid and removing the skin-piercing element prior to a reflex action by the piercing of the skin, wherein the skin-piercing element comprises: a micro-sampler having an open capillary channel for drawing liquid from the epidermis; and an analysis tool to place liquid from the open capillary channel onto the analysis tool within an interval that reduces evaporation of sample that significantly affects test results, and the placing liquid occurs within 500ms of the drawing liquid.

3. A blood compression and sampling device, comprising:

a micro-sampler configured to collect bodily fluid from an epidermis prior to a reflex action occurring, the micro-sampler comprising:

a main body which is provided with a plurality of grooves,

a shaft having a pointed end extending from the body to penetrate the skin, and

an open capillary channel extending along the axis having a capillary channel opening for collecting the body fluid by capillary action, the capillary channel being hydrophilic, the capillary channel opening being located between 350 μm and 600 μm from the tip portion.

4. The device of claim 3, wherein the capillary channel opening is located about 425 μm from the tip portion.

5. The device of claim 3, wherein said point has a cutting edge angle of from 20 ° to 40 °.

6. The device of claim 3, wherein the capillary channel has an aspect ratio of from 0.7 to 1.6.

7. The apparatus of claim 3, further comprising:

a firing mechanism to fire the micro-sampler into the epidermis, the firing mechanism comprising a pressure sensitive trigger configured to fire the firing mechanism when a force of at least 6N is applied to the epidermis.

8. The apparatus of claim 3, further comprising:

a gauge in which the micro-sampler is loaded, the gauge comprising a compression ring made of a rigid inner ring overmolded with a flexible material.