Device and method for dried fluid spot analysis

Abstract

A lab-on-chip-based system is described for the direct and multiple sampling, control of the volume, fluid filtration, biochemical reactions, sample transfer, and dried spot generation on the conventional and commercial cards for dried fluid spot. Within an all-in-one integrated holder, the invention allows the complete process required to ensure a quantitative analysis of blood, plasma or any other fluids, modification and enrichment of molecule subsets, and formation of a dried fluid spot on the specific spot location of a passive cellulose, non-cellulose, absorbent, or non-absorbent membrane material sampling.

Claims

1. A fluid sampling device for sampling a biological sample on a dried spot sampling medium, the device comprising: a fluid channel having an inlet and an outlet, the inlet and the outlet arranged at different locations of the device, a dried fluid spot to be formed at the outlet, the fluid channel configured to induce a capillary action on a fluid moving from the inlet to the outlet; and a cavity arranged at the location of the outlet of the device, the cavity configured to form a space between the outlet and the dried spot sampling medium when the dried spot sampling medium is placed onto the cavity.

2. The device according to claim 1, wherein the device includes a plurality of fluid channels.

3. The device according to claim 1, further comprising: a lid configured to bring the dried spot sampling medium into contact with the outlet of the fluid channel when the dried spot sampling medium is placed onto the cavity.

4. The device according to claim 1, wherein the fluid channel includes a filter at the inlet.

5. The device according to claim 1, wherein the fluid channel is biochemically functionalized.

6. The device according to claim 2, wherein the plurality of fluid channels are biochemically functionalized in a different manner from each other.

7. The device according to claim 1, wherein the location of the inlet is arranged on a different surface of the device compared to the location of the outlet.

8. The device according to claim 1, wherein the cavity is formed by a spacer arranged on the device.

9. The device according to claim 1, wherein a contact between the dried spot sampling medium and the fluid at the outlet generates a dried fluid spot on the dried spot sampling medium.

10. The device according to claim 1, wherein the dried spot sampling medium includes a card.

11. A fluid sampling device for sampling a biological sample, the device comprising: a dried spot sampling medium for sampling the biological sample; a fluid channel having an inlet and an outlet, the inlet and the outlet arranged at different locations of the device, a dried fluid spot to be formed at the outlet, the fluid channel configured to induce a capillary action on a fluid moving from the inlet to the outlet; and a cavity arranged at the location of the outlet of the device, the dried spot sampling medium covering the cavity such that the cavity forms a space between the outlet and the dried spot sampling medium.

12. The device according to claim 11, wherein the dried spot sampling medium is removably attached to the cavity.

13. The device according to claim 11, further comprising: a lid configured to urge the dried spot sampling medium into contact with the outlet of the fluid channel.

14. The device according to claim 11, wherein the cavity is formed by a spacer arranged on the device.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The invention will be better understood below, in particular with non-limiting examples illustrated by the following figures:

(2) FIG. 1 shows a first embodiment (cross section, side view) of the device according to the invention comprising a card holding element with a lid, in a phase where the lid is not fixed to the card holding element.

(3) FIG. 2 shows another embodiment of the invention with a card holding element including several fluid channels.

(4) FIG. 3 shows the same embodiment of FIG. 1 but with the lid fixed to the card holding element.

(5) As shown in the figures, a flexible conventional or non-conventional sampling card 5 is fixed to a card holding element 4 which includes a cavity defined by a bottom surface surrounded by at least one spacer 1 which maintains the storage card above the bottom surface (see FIG. 1). The card holding element 4 contains at least one fluid channel 3 (see also FIG. 2) defined between an outlet 7 located in the bottom surface and an inlet 2 located in another face of the card holding element 4. Advantageously the card holding element 4 contains several fluid channels 3 which are set in-line to allow multiple and independent samplings according to the number of spot locations 8, around said outlets 7. Each channel 3 is designed to produce a dried fluid spot within those spots 8. The channels 3 may have different geometries. They may have a linear or a curved shape. Preferably the channel section, length and material are chosen in a way as to induce a capillary effect, i.e. a driving force, to the fluid sample, which is entering the channel 3.

(6) In operation, a fluid to analyze is brought into contact with the inlet(s) 2 (see FIGS. 1 and 2). At least one drop of the fluid is then traveling mechanically or by capillarity through the channel 3. It should be underlined that any suitable element, e.g. mechanical, can be added to the device for facilitating and/or increasing the fluid motion through the inlet filter membrane 2 or along the channel 3. Usual traveling time through the channel(s) takes a few seconds. Advantageously the inlet 2 is provided with a filter membrane that, for instance, may filtrate the fluid and separate red cells from the blood. Interestingly, enzymes, antibodies or chemicals can be blotted on this membrane to treat the biological fluid before its transfer toward the channel 3.

(7) The channel 3 is advantageously calibrated to accept a predetermined volume of fluid (typically 5-50 L). This volume can be modified according to the required analysis. Furthermore, the channel 3 may incorporate different in-situ functionalization to provide specific biochemical properties. In this way, chemical, antibody, or enzyme blotting may be introduced into the channel 3 for providing analyte target enrichment and/or modification. As example, enzyme, like cytochrome P450 or trypsin can be introduced to ensure phase I drug metabolism and protein digestion, respectively.

(8) Simultaneously, the channel 3 may also be used for the separation of molecules of interest according to their hydrophobic, hydrophilic, anion and cation exchange, metal and immune affinities as example. Several dimensions of chemical properties can also be assigned to different sections of a same channel 3 for serially enriched molecule subset according to different chemical properties. Fractionation of the channel 3 can provide the possibility of combining sequential analyte treatments. A first portion can assume the enrichment process for a specific target or subclass of analytes whereas a second can induce the biochemical or chemical modification of this analyte subset.

(9) In another configuration, these different sample pretreatments may be independently carried out on each channel 3. In this manner the same fluid drop can be brought to multiple dried spots 8 having each a different molecular signature (FIG. 2). This feature is particularly interesting associated to clinical research by allowing the possibility of increasing the selectivity and the sensitivity of the analysis. When it has reached the outlet 7, the fluid preferably forms a static dome shaped object. Such an object results from the predefined calibrated volume of fluid and the capillary forces at the outlet 7.

(10) The flexible card 5 is then forced towards the outlet 7, either by directly pushing the card 5 with the fingers or via a lid 6 (see FIGS. 1 and 3) which could be clipped to the card holding element 4.

(11) Any other suitable pushing means can be used for bringing the card 5 into contact with the outlet 7. For instance, a strip attached to the holding element 4 can be used to manually slide the holding element 4 along the lid 6. This operation allows the lid 6 to be brought in front of the lip, which ensure the contact between the card 5 and the fluid at the outlet 7.

(12) The contact between the card 5 and the fluid at the outlet 7 generates a dried fluid spot on the card 5.

(13) Advantageously the outlet 7 may form a right angle with an aperture oriented toward the card 5.

(14) As mentioned previously the lid 6 may be replaced by another pushing means such as a finger. However, it offers a protection for the sample particularly for shipment of the paper card to the laboratory.