CN1845704A - Sampling device with capillary action - Google Patents

Abstract

The present invention provides an apparatus for receiving a liquid sample, said liquid sample being a bodily fluid sample to be subjected to further analysis. The apparatus includes: a body having at least a primary surface and a secondary surface; a sample receiving chamber located within the body and having an inlet end opening onto the secondary surface of the primary surface of the body; and a conduit located within the body, extending from an outlet end of the sample receiving chamber, and arranged such that liquid enters the conduit from the outlet end via capillary action.

Description

Sampling device with capillary action

The present invention relates to a device for receiving a sample of fluid, in particular, though not exclusively, the invention relates to a device for receiving a sample of bodily fluid, such as blood, so that tests can be performed on the sample.

Known liquid sample receiving devices for blood glucose monitoring absorb finger prick blood very quickly, which is presently not a problem because the measurement methods currently employed do not require the blood to be actively moved, or driven by capillary action.

However, there are problems with the use of fingersticks in diagnostic devices that require the sample to be moved in an active manner, or that require capillary action to drive the sample.

In a first aspect, the present invention provides a device for receiving a liquid sample, the device comprising:

a body having at least a major surface and a minor surface;

a sample receiving chamber located within the body and having inlet ports opening on the major and minor surfaces of the body; and

A conduit is located within the body and extends from the outlet end of the sample receiving chamber, the conduit being arranged such that liquid enters the conduit from the outlet end by capillary action.

The present invention allows the user to deposit a liquid sample into or onto the device at the sample receiving chamber. The user can remove the sample source (such as a finger) and the device secures the supply of fluid down the conduit, for example, so that the test can be performed in another area of the device. This approach is important for diagnostic devices for blood samples when the test result is not immediate, such as immunoassays requiring immunological binding of reagents or biological enzymatic reactions associated with clotting time measurements. It is also important for devices where diagnostics or tests have to be performed remotely from the sample receiving chamber. Another advantage is that the sample receiving chamber acts as a reservoir which can then supply the device with the remaining sample even when the user is not in contact with the device and eliminates the need for the user to be in constant contact with the device during filling. This is particularly advantageous for elderly persons, who may find it difficult to maintain constant contact with a device, which may be of small size. Furthermore, it reduces the likelihood of device failure if the liquid source is removed at any point during filling resulting in underfill or the introduction of air bubbles.

The chamber may be used in devices that have a fill time that is greater than the time a user would simply present a liquid source to the device and then remove it, eg, a fill time of one second or longer.

The device of the invention may be a device for use in chemical (especially biochemical or clinical) testing procedures, commonly known as capillary filling testing devices. A capillary fill test device is typically used in conjunction with a second device, typically an electronic instrument designed to detect the presence, or extent of a predetermined interaction, of one or more analytes in a liquid sample or in a liquid sample, It has one or more other components of the device. The component may be an electrode structure and/or one or more components that interact with the fluid or react with the analyte. Electronic instruments can be used to assess the sample liquid in the device, most typically using optical or electrical measurement techniques after a predetermined sample reaction period. Capillary filling devices are often designed to sit within the electronic instrument before the device is loaded with a fluid sample. When the capillary filling device is properly located in the instrument, the sample receiving chamber is external to the instrument and is accessible to the user, the area under test of the device is arranged in electrical communication or optical transmissive/reflective communication with the sensing element, said The sensing element is capable of detecting and reporting the state or change of state of the liquid after or during a preset period of time. The bulk of the test liquid is delivered to the sample receiving chamber by being drawn by capillary action (and possibly other forces), into and through the conduits, and into the region of the device where the test is performed. The apparatus may be equipped with sensors for detecting the flow of test liquid through the conduit; optionally, the apparatus may be designed to use this sensed flow to initiate the test procedure. In some liquid testing applications, eg, in certain instruments designed for use with capillary filling devices to measure blood coagulation characteristics, the flow rate of liquid through a capillary flow conduit is detected and used as a parameter in the testing procedure. In the test applications described above, the catheter is additionally used to provide a mechanism for measuring the flow properties, ie viscosity, of the test liquid as it is delivered to the test area.

The body of the device may be generally rectilinear in shape, which is the conventional style for capillary testing devices. These strips may have end walls, side walls and/or top and bottom surfaces or portions thereof which are not parallel to each other. Alternatively, it may be cylindrical, wedge-shaped, disc-shaped, or any other convenient shape, provided it has a major and minor surface on which the inlet end of the sample receiving chamber opens.

The inlet port of the sample receiving chamber is open on the major outer surface and the minor outer surface of the main body. The major surface and the minor surface can be generally perpendicular to each other, and the surface area of the minor surface can be significantly smaller than the surface area of the major surface. The minor surface can be an end wall or a side wall, and the major surface can be a top surface (when eg the body is rectilinear or wedge-shaped or disc-shaped), in which case the sides of the device cannot be considered major surfaces. In one embodiment, the minor surface is the end wall and the major surface is the outer surface (when eg the body is cylindrical). Regardless of the shape of the body, the opening at the inlet end is preferably continuous within the major and minor surfaces.

The portion of the sample receiving chamber opening on the minor surface may be smaller than the portion of the sample receiving chamber opening on the major surface. For example, the area of the opening of the sample receiving chamber on the major surface may be 1.3 to 3 times, and in one embodiment, 1.6 times, the area of its opening on the minor surface.

The sample receiving chamber can taper from the inlet end to the outlet end, and can be generally V-shaped or U-shaped. For example, the width of the inlet port may be about 10-15 times the width of the outlet port, and may be 0.5-1.5 times the length of the sample receiving portion.

The conduit is designed so that the liquid sample can move by capillary action, although other forces can act on the liquid, such as hydrostatic pressure and/or positive displacement, causing the liquid to move along the conduit. For example, the largest dimension of the catheter may be less than 0.5, 0.4 or 0.3 mm when viewed in a section perpendicular to the longitudinal axis. In one embodiment, the largest dimension is 0.25-0.3mm, and may be about 0.28mm. Catheters can have a Reynolds number of less than about 200, which is calculated according to the following formula:

$\mathrm{<span\; class="notranslate">\; Re</span>}<span\; class="notranslate">\; =</span>\frac{\mathrm{<span\; class="notranslate">\; \&rho;Vd</span>}}{\mathrm{<span\; class="notranslate">\; \&eta;</span>}}$

Wherein, Re=Reynolds number, ρ=fluid density, V=fluid velocity, d=length scale, η=dynamic viscosity. A Reynolds number of 200 or less will cause conduits (which can be thought of as microstructures or microchannels) to be passively filled by surface tension alone (capillary action).

At least the sample receiving chamber and the conduit are conveniently coated with a hydrophilic coating, which may be on any or all walls. The coating may provide a contact angle of 90° or less, 30° or less, or 20° or less. The contact angle may be 5-15°, and may be 11°. A contact angle of 110° can be provided provided it is applied to only one wall. The contact angle measurement method is described in "Fundamental and Applications of Microfluidics", Nguyen & Werely, Artech House, 30 Sept 2002, ISBN 1580533434, p. 46.

The liquid that can be sampled is any liquid. In preferred embodiments, the fluid is a bodily fluid such as whole blood, plasma, interstitial fluid, cerebrospinal fluid (CSF), urine, serum, saliva, tears and sweat.

In a second aspect, the present invention provides a device for receiving a liquid sample, the device comprising:

a body having at least an end wall;

a generally V-shaped sample receiving chamber located within the body and having an inlet port opening into the end wall of the body; and

A conduit is located within the body and extends from the outlet end of the sample receiving chamber, the conduit being arranged such that liquid enters the conduit from the outlet end by capillary action.

The devices of the present invention may be used to receive blood that has undergone coagulation measurements and/or other hemostatic measurements such as prothrombin time measurements. They can also be used to receive body fluids undergoing immunoassays, hormone measurements, cardiology marker measurements, cancer marker measurements, infectious disease substances measurements, etc. These tests can be performed in the analysis chamber of the device.

The preferred features of each aspect of the invention are mutatis mutandis the preferred features of other aspects.

The invention will be further described with reference to the accompanying drawings, in which:

Figure 1 is a partial perspective view of an embodiment of the present invention;

Fig. 2 is the plan view of Fig. 1 device;

Fig. 3 is a sectional view along the X-X line of Fig. 2;

Fig. 4 is the perspective view of the section along the X-X line of Fig. 2;

Figures 5a and 5b are plan views of two alternative embodiments of the present invention;

Figure 6 is a graph of fill time versus volume of whole blood added to the device of the present invention;

Figure 7 is a partial perspective view of the front end of another embodiment of the present invention;

Figure 8 is a plan view of the device of Figure 7; and

Fig. 9 is a cross-sectional view along line X-X in Fig. 8 .

Referring to Figures 1-4, the device 1 is partially shown. The device 1 has a top (major) surface 2 , an end (secondary) surface 3 and respective sides 4 . The bottom surface of the device cannot be seen. The device 1 tapers towards the end surface. In some embodiments, the device 1 does not have this tapered shape, in other embodiments the device 1 has a hammerhead shape. The sample receiving chamber 5 is recessed in the device 1 such that it opens on the top surface 2 and the end surface 3 . In an alternative embodiment, the sample receiving chamber 5 opens on the top surface 2 and the side surface 4 .

The sample receiving chamber 5 has an inlet end, and an outlet end leading to a conduit 6 . The inlet end is substantially larger than the outlet end such that the sample receiving chamber 5 tapers in a V shape towards the outlet end. Alternatively, the sample receiving chamber is generally V-shaped or U-shaped as shown in Figures 5a and 5b. In one embodiment, the sample receiving chamber 5 is tapered such that the value of dimension A decreases from the inlet end to the outlet end. In general, the sample receiving chamber can be of any shape and size so long as the liquid sample can pass from the inlet port to the outlet port by capillary action. In order to accelerate the passage of liquid within the sample receiving chamber, the shape and dimensions of the sample receiving chamber are chosen such that the capillary action at the outlet end is greater than the capillary action at the inlet end.

As shown, conduit 6 is a recessed channel in top surface 2 . Although not shown, the duct 6 is closed by a thin layer placed on the top surface 2 . This layer may cover all or a portion of the sample receiving chamber 5, although it is not preferred that the layer cover all of the sample receiving chamber 5 because the additional friction provided by the layer on the chamber 5 reduces the amount of fluid that can travel down the conduit 6. Due to the speed of movement, it is advantageous that part of the sample receiving chamber 5 is covered, which covers breaks the surface tension of the sample and facilitates entry of the sample into the conduit 6 when the sample is applied to the sample receiving chamber. Partial coverage also allows the addition of sample volumes greater than can be added to the sample receiving chamber. The other end of the conduit 6 leads to an area of the device (not shown) where analysis or testing can be performed.

In one embodiment, dimension A is 0.9mm, B is 2.5mm, C is 0.2mm, D is 3mm and E is 0.2mm.

Devices of the invention can be prepared using a variety of techniques known in the art. For example, injection molding using an appropriate mold or microinjection molding can be used. Alternatively, embossing techniques that emboss structures into the material and techniques using silicon etching and/or photolithography may also be used.

As another alternative, the device may be prepared by laminating two or more layers, see Figure 7, the device may comprise three layers. Base layer 7 forms the bottom of chamber 5 and channel 6 . The intermediate layer 8 has cutouts through it forming the walls of the chamber 5 and the channel 6 . Top layer 9 forms the top surface of trench 6 . In the illustrated embodiment, the top layer 9 partially covers the sample receiving chamber 5 , which is formed by the cutout face of the layer 8 and the top surface of the base layer 7 . The plan view of FIG. 7 is shown in FIG. 8 , and the cross-sectional view of FIG. 8 along line X-X is shown in FIG. 9 .

In one embodiment, dimension A is 0.275mm, B is 3mm, C is 0.3mm, D is 2.5mm, E is 0.175mm and F is 2mm.

The laminated device of the present invention may be prepared by the method described in UK patent application 0327094.9, the disclosure of which is incorporated herein by reference.

Example

Injection molded polystyrene devices with sample receiving chambers as shown in Figures 1-4. These devices were then treated with plasma-enhanced chemical vapor deposition to coat the surface with a layer of hydrophilic molecules such that the treated contact angle was about 11°. The above techniques are well known to those skilled in the art. The device was then laminated with a thin hydrophilic layer (contact angle 11°) such that the thin layer covered the conduit 6 but not the sample receiving chamber 5 .

Different volumes of fresh whole blood are pipetted onto the sample receiving chamber 5 (blood from a finger prick can also be applied directly to the sample receiving chamber). The time for blood to travel down the catheter 6 to a fixed point is measured. A plot of the fill time versus volume of whole blood added to the device is shown in FIG. 6 .

It can be seen that volumes of 5 μl or less result in a fill time of greater than about 20 seconds, volumes of 7 μl or greater have a lesser effect on the fill time.

Claims (9)

1. be used to receive the device of fluid sample, this device comprises:

At least the main body that has first type surface and subsurface;

Sample receiving chamber, it is positioned at main body and has opening at the first type surface of main body and the arrival end of subsurface; With

Conduit, it is positioned at main body and extends from the port of export of sample receiving chamber, and this conduit is arranged so that liquid enters conduit by capillarity from the port of export.

2. the described device of claim 1, wherein the opening of the arrival end of sample receiving chamber is successive in first type surface and subsurface.

3. claim 1 or 2 described devices, wherein main body is substantially straight line bar shaped or wedge shape or disc.

4. the described device of claim 3, wherein subsurface is the end wall or the sidewall of main body, first type surface is the top surface of main body.

5. claim 1 or 2 described devices, wherein main body is substantially cylindrical.

6. the described device of claim 5, wherein subsurface is an end wall, first type surface is the outer surface of cylinder.

7. each described device in the aforementioned claim, wherein sample receiving chamber is tapered to the port of export from arrival end.

8. the described device of claim 7, wherein sample receiving chamber is substantially V-arrangement or U-shaped.

9. be used to receive the device of fluid sample, this device comprises:

At least the main body that has end wall;

V-arrangement sample receiving chamber substantially, it is positioned at main body and has the arrival end of opening at the main body end wall; With

Conduit, it is positioned at main body and extends from the port of export of sample receiving chamber, and this conduit is arranged so that liquid enters conduit by capillarity from the port of export.

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