Device for taking a liquid sample by capillarity and associated analysis method
10966645 · 2021-04-06
Assignee
Inventors
Cpc classification
A61B5/150251
HUMAN NECESSITIES
B01L3/5027
PERFORMING OPERATIONS; TRANSPORTING
A61B5/150068
HUMAN NECESSITIES
B01L2200/0684
PERFORMING OPERATIONS; TRANSPORTING
A61B5/157
HUMAN NECESSITIES
A61B5/151
HUMAN NECESSITIES
A61B5/150748
HUMAN NECESSITIES
A61B5/15142
HUMAN NECESSITIES
A61B5/15105
HUMAN NECESSITIES
A61B5/150755
HUMAN NECESSITIES
A61B5/150412
HUMAN NECESSITIES
B01L2300/161
PERFORMING OPERATIONS; TRANSPORTING
International classification
A61B10/00
HUMAN NECESSITIES
A61B5/157
HUMAN NECESSITIES
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A device for taking a sample of liquid by capillarity, including a channel for flow of the liquid delimited by two internal walls of the device between which a channel bottom extends, the distance separating the two internal walls decreasing in the direction of the channel bottom, the channel extending between a first collecting end, open onto outside of the device and configured to receive the liquid, and a second end, to enable the liquid to flow by capillarity along the channel bottom from the first end towards the second end. The channel includes, at the second end, a blocking structure to block the flow of liquid in the channel from the first end towards the second end.
Claims
1. A device for taking a sample of liquid by capillarity, comprising: a channel for flow of the sample of liquid delimited by two internal walls of the device between which a channel bottom extends, a distance separating the two internal walls decreasing in a first direction of the channel bottom, the channel extending in a rectilinear direction between a first end, open onto outside of the device and configured to receive the sample of liquid, and a second end, to enable the sample of liquid to flow by capillarity along the channel bottom from the first end towards the second end, the channel comprising, at the second end, a first blocking means configured to block a flow of liquid in the channel from the first end towards the second end, and the channel comprising, on a top side of the channel below a channel upper surface of the channel, a second blocking means configured to block a flow of liquid in the channel in a second direction from the channel bottom to the upper surface of the channel and, wherein: the second blocking means comprises at least one first blocking ridge extending in the rectilinear direction, formed on each of the two internal walls, the at least one first blocking ridge being disposed at a same height on each of the two internal walls above the channel bottom, and forms a step in each of the two internal walls in a direction from the top side of the channel to the channel bottom, and the channel has a first width below the second blocking means and a second width above the second blocking means, a minimum value of the second width being greater than a maximum value of the first width.
2. The device according to claim 1, wherein the channel comprises the first blocking means in a form of a closure wall of the channel.
3. The device according to claim 1, wherein: the first blocking means comprises at least one second blocking ridge formed on at least one internal wall of the device and broadening at least part of the channel at the second end, and the second width is at least twice the first width.
4. The device according to claim 1, wherein the channel comprises the first blocking means in a form of a coating made locally hydrophobic.
5. The device according to claim 1, wherein the channel comprises the first blocking means in a form of a broadening of the channel bottom, configured to reduce capillary force applied to the sample of liquid, when the sample of liquid progresses towards the second end.
6. The device according to claim 1, wherein the channel is divided into at least a lower part, the channel bottom and an upper part so that the lower part is situated between the channel bottom and the upper part, the lower and upper parts being delimited by the two internal walls, the lower part having a capillary force greater than that of the upper part to allow a spontaneous capillary flow of the sample of liquid along the channel bottom from the first end towards the second end.
7. The device according to claim 1, wherein the two internal walls are secant to form the channel bottom at their intersection.
8. The device according to claim 1, wherein the channel comprises, on at least part thereof, at least one reagent in at least one of dry and lyophilised form.
9. The device according to claim 1, wherein a height of the channel remains constant while extending along the channel bottom from the first end towards the second end.
10. The device according to claim 6, wherein a height of the lower part of the channel is less than or equal to 5 mm.
11. The device according to claim 1, wherein the channel extends in a concave direction from the first end towards the second end.
12. The device according to claim 1, further comprising, at the first end of the channel, a contact surface enabling the sample of liquid to be taken, lying in a plane perpendicular to at least one internal wall of the device.
13. The device according to claim 12, wherein the contact surface comprises a support surface against which a body element is configured to bear for the sample of liquid to be taken.
14. The device according to claim 12, wherein the contact surface comprises a flow opening configured to emerge in the channel.
15. The device according to claim 1, wherein the two internal walls of the device are produced from a transparent or translucent material.
16. The device according to claim 1, further comprises piercing means to enable a skin to be pierced to collect the sample of liquid.
17. The device according to claim 1, wherein height of the channel is variable, increasing at least over a first portion of the channel.
18. The device according to claim 17, wherein the channel comprises a concave part, extending over a second portion lying between a first distance and a second distance with respect to the first end of the channel.
19. A method for analyzing a sample of liquid taken by a device according to claim 1, wherein the device is subjected to analysis means configured to analyze liquid contained in the channel at at least one predetermined analysis zone of the channel.
20. A device for taking a sample of liquid by capillarity, comprising: a channel for flow of the liquid delimited by two internal walls of the device between which a channel bottom extends, a distance separating the two internal walls decreasing in a first direction of the channel bottom, the channel extending between a first end, open onto outside of the device and configured to receive the sample of liquid, and a second end, to enable the liquid to flow by capillarity along the channel bottom from the first end towards the second end, the channel comprising, at the second end, a first blocking means configured to block a flow of liquid in the channel from the first end towards the second end, and the channel comprising, on a top side of the channel below a channel upper surface of the channel, a second blocking means configured to block a flow of liquid in the channel in a second direction from the channel bottom to the upper surface of the channel, wherein the channel comprises a lower part and an upper part, the lower part having a bottom portion with a dihedron shape having a half-angle a, the liquid having an angle θ of contact with the two internal walls on the lower part, the lower part having a width d, the upper part having a width w1 where the upper part meets the lower part, the upper part having a width w2 greater than width w1 at an upper surface of the channel and a height H, and the two internal walls in the upper part having an angle of inclination of β with respect to a bottom to top direction of the channel and a length L in a third direction from where the upper part meets the lower part to the upper surface, wherein the following relations hold:
H =L ×cos β,
w.sub.2/(2L+(w.sub.1−d))<cos θ, and
H <(w.sub.1cos β(1−cos θ)+d cos βcos θ]/ [2(1−sin β)).
21. A device for taking a sample of liquid by capillarity, comprising: a channel for flow of the sample of liquid delimited by two internal walls of the device between which a channel bottom extends, a distance separating the two internal walls decreasing in a first direction of the channel bottom, the channel extending between a first end, open onto outside of the device and configured to receive the sample of liquid, and a second end, to enable the sample of liquid to flow by capillarity along the channel bottom from the first end towards the second end, the channel comprising, at the second end, a first blocking means configured to block a flow of liquid in the channel from the first end towards the second end, and the channel comprising, on a top side of the channel below a channel upper surface of the channel, a second blocking means configured to block a flow of liquid in the channel in a second direction from the channel bottom to the upper surface of the channel, wherein the channel comprises a lower part and an upper part, the lower part having a bottom portion with a dihedron shape having a half-angle a, the liquid having an angle θ of contact with the two internal walls on the lower part, the lower part having a width d, the upper part having a height H, and the two internal walls in the upper part having an angle of inclination of β with respect to a bottom to top direction of the channel and a length L in a third direction from where the upper part meets the lower part to the upper surface, wherein the following relations hold:
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) The invention can be better understood from a reading of the following detailed description of non-limitative example embodiments thereof, and from an examination of the schematic partial figures in the accompanying drawing, in which:
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(23) In all these figures, identical references may designate identical or similar elements.
(24) In addition, the various parts depicted in the figures are not necessarily shown according to a uniform scale, in order to make the figures more legible.
DETAILED DISCLOSURE OF PARTICULAR EMBODIMENTS
(25)
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(27) In accordance with the invention, the device 1 comprises a channel 2 for flow of the liquid L delimited by two internal walls 3 and 4, or lateral walls, between which a channel bottom 5 extends. The distance D, visible in
(28) Thus the overall form of the channel 2, defined by the internal walls 3 and 4, thins from the upper surface 18 of the channel 2, that is to say the surface joining the ends of the internal walls 3 and 4 opposite to the channel bottom 5, towards the channel bottom 5, the upper surface 18 of the channel 2 being open to the outside E. The form of the channel 2 thinning from this upper surface 18 towards the channel bottom 5 makes it possible to obtain a capillarity force of the channel 2 that is greater at the channel bottom 5 than at the upper surface 18 open to the outside E.
(29) Moreover, in order to control the filling of the channel 2 with liquid L and to prevent any contamination of the outside E by the liquid L, one or more means for blocking the flow of liquid L along the channel bottom 5 can be provided. These means make it possible to block the flow of liquid at the second end or upstream of the latter.
(30) Such a blocking means may for example be in the form of a wall 17 for closing the channel 2, situated in particular at the second end 7 of the channel 2. Such a closure wall 17 can extend transversely between the internal walls 3 and 4 to close the channel 2, in particular at the second end 7.
(31) Such a blocking means may also be in the form of a coating made locally hydrophobic (not shown) in order to prevent the flow of liquid L. This coating may be situated in particular at the second end 7 of the channel 2 and for example at the channel bottom 5 and/or at one or more of the two internal walls 3 and 4.
(32) In the example shown in
(33) The blocking ridges 9 may make it possible to stop the capillary filling of the liquid L in the channel 2 and may thus make it possible to perfectly control the volume of liquid sample L taken by the device 1.
(34) A blocking means may also comprise a gradual broadening of the channel bottom 5, upstream of the second end 7. Such a broadening reduces the capillarity force applied to the liquid, which constitutes the engine for the flow. The result is a reduction in the rate of progress of the liquid along the channel bottom 5. When the channel bottom 5 is a line, formed by the intersection of the lateral walls 3 and 4, at the broadening, the channel bottom 5 takes the form of a flat surface, the width of which increases gradually from a negligible value (the width of a line) to 50 μm, or even between 150 and 200 μm.
(35) The blocking means described above may be combined. In particular, the device may comprise a first blocking means disposed upstream of a closure wall of the channel. Such a combination slows down the flow of liquid upstream of said closure wall.
(36) The device 1 may comprise a zone for filling of the liquid sample L situated at the first end 6 of the channel 2 and a zone for stopping the liquid L situated at the second end 7 of the channel 2.
(37) An analysis zone 15, in particular an optical measurement zone, can be provided over the extent of the channel 2, in particular in a central part of the channel 2, as can be seen in
(38) Moreover, as can be seen more easily in
(39) Separation between the lower 11 and upper 12 parts of the channel 2 can be achieved by means 13 for anchoring the liquid L on at least one internal wall 3, 4 of the device 1, affording a blocking of the flow of liquid L from the lower part 11 towards the upper part 12.
(40) More particularly, as can be seen in particular in
(41) The anchoring ridges 13 can thus prevent a flow of the liquid L towards the outside E of the device 1, beyond the lower part 11 of the channel 2.
(42) In other words, by virtue of the anchoring ridges 13 and the blocking ridges 9, it is possible to maintain a confinement of the liquid L in the lower part 11 of the channel 2, as shown schematically by the zone in broken lines in
(43) The broadening of the channel 2 obtained by means of the blocking ridges 9 may depend on the angle Ω formed by a blocking ridge 9 with an internal wall 3 or 4 of the device 1 in the case of non-broadening. More specifically, in the case of non-broadening (a blocking ridge 9 not present), this angle Ω is zero. In the case of broadening, as can be seen in
(44) Moreover, the broadening obtained by the presence of anchoring ridges 13 from the lower part 11 of the channel 2 towards the upper part 12 of the channel 2 may depend on the angle formed by an anchoring ridge 13 with an internal wall 3 or 4 of the device 1 in the case of non-broadening. More specifically, in the case of non-broadening (anchoring ridge 13 not present), this angle is zero. In the case of broadening, the anchoring ridge 13 may form an angle Ω greater than 20°, being in particular equal to 90° in the example shown in
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(46) The device 1 may for example be used for sampling a drop of blood L formed at the end of a finger D.sub.g of a user, intended to be analysed.
(47) To allow the correct filling of the device 1 with the liquid L, the device 1 is placed in contact with the drop of blood by means of the first collecting end 6 of the channel 2, as can be seen in
(48) Then, as can be seen in
(49) Then, as can be seen in
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(51) Preferably, the channel bottom 5 is formed by the intersection of secant internal walls 3 and 4 as shown in
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(54) Thus, when the two lower parts 11 are put in contact at the same initial time (
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(56) In this example, the channel 2 is produced in a similar fashion to the one in the example in
(57) The device 1 in
(58) In general terms, the device 1 may comprise a reagent in the channel 2, in particular in dry or lyophilised form, intended to react with the liquid sample L, this reagent being in particular situated upstream of the second end 7 considering the flow of liquid L from the first end 6 towards the second end 7.
(59) In the case of the device 1 in
(60)
(61) In this example, the device 1 is more or less similar to that described with reference to
(62) The contact surface 14 further comprises a flow opening 16 designed to emerge in the channel 2.
(63) The contact surface 14 is advantageously intended to be approached by, or even to come into contact with, an element from which it is wished to take a sample of liquid L, this element being in particular able to be a body element, for example a finger, a lip or any other member from which it is wished to sample a bodily fluid. In this way, the contact surface 14 may be configured so as to be able to be approached by such a body element, or even to come into contact with the body element. In particular, the contact surface 14 may be curved, being oriented so as to be concave with respect to the element from which it is wished to take the liquid sample L, as can be seen in
(64) The presence of such a contact surface 14 may make it possible to increase the collection efficiency and also prevent the sampled liquid L flowing to the outside E of the device 1.
(65) Advantageously, the contact surface 14 is configured so that its central part does not come into contact with the element from which it is wished to take a liquid sample L. The flow opening 16 may be formed at least partly in the central part of the contact surface 14 so as to emerge at the lower part 11, in particular at the bottom 5 of the channel.
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(68) Thus the device 1 is overall in the form of a fine capillary V in the lower part 11 with a broadening in the upper part 12. The point formed by the channel bottom 5 forms a filament that progresses in an uninterrupted fashion by what is referred to as a Concus-Finn effect. The upper part 12 is sized so as to not fill with liquid L and can allow manipulation of the device 1.
(69) The capillary flow is facilitated by having a V-shaped dihedron. The condition for obtaining a capillary flow is the Concus-Finn condition, which is stated as follows:
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(71) where θ is the angle of contact of the liquid L with the internal walls 3 and 4, also referred to as the wetting angle or Young angle,
(72) α is the half-angle of the dihedron, as shown in
(73) For example, if α is equal to 5°, then it is necessary for θ to be strictly less than 85°.
(74) The Concus-Finn effect makes it possible to obtain a “point effect” when the liquid L flows in the channel 2, as can be seen in
(75) The so-called Concus-Finn condition disclosed above can make it possible to size the lower part 11 of the channel 2 according to the contact angle θ.
(76) However, it may be necessary in practice to take a few additional precautions to take account of surface imperfections, and thus to choose a slightly lower angle than the one obtained by the theoretical Concus-Finn formula.
(77) It is also necessary to be able to size the upper part 12 of the channel 2 so as to obtain a spontaneous capillary flow SCF that allows a flow by capillarity along the channel bottom 5 in the lower part 11, as shown in
(78) To do this, it is assumed that the width d.sub.1 of the channel 2 in the lower part 11 and the half-angle α, as both shown in
(79) Then a study carried out with the Evolver software showed that it is possible to avoid the invasion of the upper part 12 of the channel 2 by a suitable increase in the cross section of flow w.sub.1 of the upper part 12 of the channel 2, as shown in
(80) The condition for obtaining a spontaneous capillary flow SCF, determined from the Gibbs thermodynamic equation, is then written:
w.sub.2/(2l.sub.2+(w.sub.1−d.sub.1))<cos θ.
(81) Then, after the geometric consideration according to which h.sub.2=l.sub.2×cos β, the condition in order not to have spontaneous capillary flow SCF in the upper part 12 of the channel 2 is as follows:
h.sub.2<[w.sub.1 cos β(1−cos θ)+d.sub.1 cos β cos θ]/[2(1−sin β)].
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(83) Thus, for example, in the case of an angle β chosen so as to be equal to approximately 10°, as in the example in
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(85) For example, in the case in
(86) The height h.sub.2 of the upper part 12 may for example be less than 150 μm, the width w.sub.1 may for example be around 400 μm and the angle β may be around 10°.
(87) In order to have a spontaneous capillary flow SCF in the upper part 12, there is for example an advantage in having an abrupt broadening with a value w.sub.1 equal to approximately 400 μm and a height h.sub.2 strictly less than 150 μm.
(88) In the example in
d.sub.1/(2h.sub.2+d.sub.1)<cos θ
(89) Thus, in order to obtain a spontaneous capillary flow SCF, it is necessary for the ratio between the height h.sub.2 of the lower part 11 of the channel 2 and the width d.sub.1 to satisfy the following condition:
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(91) For example, for d.sub.1 equal to 150 μm and θ equal to 85°, h.sub.1 is strictly greater than 785 μm.
(92) Moreover, when a deposit of reagent, for example in dried or lyophilised form, is provided in the channel 2, this reagent being intended to react with the liquid sample L, it is desirable for the deposition of the reagent to take place as homogeneously as possible.
(93) Under these circumstances, the height H of the channel 2, and in particular the height h.sub.1 of the lower part 11 of the channel 2, is designed to remain substantially constant extending along the channel bottom 5 from the first end 6 towards the second end 7 of the channel 2.
(94) In addition, as well as being constant along the bottom 5 of the channel, the height h.sub.1 of the lower part 11 of the channel 2 must preferably be less than or equal to 5 mm, better 2 mm, or even 1 mm, or even again 0.7 mm.
(95) Furthermore, it is also desirable for the device 1 to be able to be filled with the liquid sample L without generating an excessively great formation of air bubbles.
(96)
(97) Thus
(98) The changes in the interfaces I between the liquid and the air in
(99) A comparison of
(100) When the channel 2 extends in a convex direction (the case in
(101) Under these conditions, the risk of formation of an air bubble, in particular at the anchoring ridge 13, is great. This is because the tangent T to the interface I, and the anchoring ridge 13, may be merged with the normal N to the anchoring ridge 13, or even exceed it, depending on local heterogeneities, for example a fluctuation in the surface state. This configuration is propitious to a filling of the upper part 12 that is faster than the filling of the lower part 11 of the channel 2, and this may thus give rise to the trapping of an air bubble, in particular at the anchoring ridge 13.
(102) Conversely, when the channel 2 extends in a rectilinear direction (the case in
(103)
(104) In this example, the device 1 comprises, as for the example embodiment in
(105) The contact surface 14 further comprises a flow opening 16 designed to emerge in the channel 2.
(106) The contact surface 14 is itself structured so as to assist the emergence of the bodily fluid L issuing from the body element. Thus it comprises a support surface 20 against which the body element is intended to bear.
(107) The support surface 20 is annular and centred with respect to the flow opening 16. In particular, the support surface 20 is, in this example, formed by a torus having a thickness between for example 1 and 5 mm and a diameter between for example 5 mm and 1.5 cm.
(108) The support surface 16 in the form of a circular torus can make it possible to produce a protrusion that can serve as a support for the body element, for example a finger around the sampling zone of the finger, that is to say the zone where a drop of blood forms from the sampling, for example after action of a piercing means.
(109) Moreover, the device 1 comprises a piercing means, in particular in the form of a needle 21, to enable the skin to be pierced in order to collect the liquid sample L. This needle 21 is preferentially situated close to the first end 6 of the channel 2.
(110) The needle 21 may be able to move in the device 1 in order to perform the step of incision or piercing of the skin when the body element is placed in abutment on the support surface 20. Thus the needle 21 able to move in the device 1 can be deployed so as to be applied quickly against the body element, so as to form an incision in the latter. Then it can be retracted in the device 1. Thus the needle 21 can be deployed, from a retracted position as illustrated in
(111)
(112) Elastic return means may for example be provided inside the device 1 to enable the piercing means 21 to be moved from the retracted position (illustrated in
(113) In a variant that is not illustrated, the needle 21 may be fixed. In this case, the device 1 provided with such a fixed needle may first of all be used in a projection instrument enabling the needle to strike the skin of the patient at a speed for the projection and a travel for the piercing depths necessary for producing a sufficient incision to make a drop of liquid sample L, for example blood, emerge on the surface of the skin, and then for retracting the needle at a controlled speed. Then the device 1 can be used to take the liquid sample L thus obtained, by means of the first end 6 of the channel 2.
(114)
(115)
(116) In this example, the support surface 20 is no longer in the form of a circular torus as in
(117) In the examples in
(118) Another example embodiment of a sampling device 1 according to the invention has moreover been shown with reference to
(119) More precisely,
(120) In this embodiment, the height H of the channel 2 increases in a first portion P1 of the channel 2, this first portion P1 being situated between a first distance D1 and a second distance D2 with respect to the first end 6. In addition, the height H of the channel 2 decreases in a second portion P2 of the channel 2, this second portion P2 being in particular situated between the second distance D2 and the second end 7 of the channel 2 where the blocking means 9 is situated.
(121) In particular, in this example and in no way limitatively, the first distance D1 is zero so that the first portion P1 extends from the first end 6 as far as the second distance D2 measured from this first end 6.
(122) Moreover, preferentially, in the first portion P1, the channel 2 follows a concave form so that a segment joining two points on the channel 2 is not necessarily included in this channel 2. This concave form may allow a rapid increase in the height H of the channel 2.
(123) The first portion P1 extends as far as the second end 7.
(124) In the example shown in
(125) On the first portion P1, the height h.sub.1 of the lower part 11 of the channel 2 is constant, while the height h.sub.2 of the upper part 12 of the channel 2 increases gradually according to the distance with respect to the first end 6. In particular, close to the first end 6, the channel 2 extends in a concave direction.
(126) It has in fact been found that such a concave form, close to the first end 6, allows better filling of the channel 2.
(127)
(128) It is thus possible to view the change in the interface I between the liquid L and the air A in the channel 2 of the device 1. Thus, as described previously with reference to
(129) Moreover, the increase in the height H of the channel 2 as described previously may advantageously make it possible to provide a large optical measuring zone 15, for example with a width I.sub.m of a few millimetres, for example between 3 and 4 mm. This optical measuring zone 15 is for example situated between the first portion P1 and the second end 7, as shown in
(130) Naturally the invention is not limited to the example embodiments that have just been described. Various modifications can be made thereto by a person skilled in the art.
(131) The expression “comprising a” must be understood as being synonymous with “comprising at least one”, unless the contrary is specified.