Hand-held microfluidic detection device that uses a parasitic light suppressing mechanism to reduce background noise
10859489 · 2020-12-08
Assignee
- FUNDACIÓ INSTITUT DE CIÈNCIES FOTÒNIQUES (Castelldefels, ES)
- INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS (Barcelona, ES)
- IMAGINE OPTIC SPAIN SL (Sant Just Desvern, ES)
Inventors
- Romain Quidant (Castelldefels, ES)
- Luis Miguel Fidalgo (Castelldefels, ES)
- Rafael Porcar (Castelldefels, ES)
Cpc classification
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
The present invention relates to a hand-held microfluidic detection device, comprising: a microfluidic cell (M) having at least one chamber intended to at least contain a sample; a support (S) comprising a housing for the removable attachment thereto of the microfluidic cell (M); excitation light means arranged at least in part in the support (S) to side illuminate the at least one chamber of the microfluidic cell (M) to excite the sample contained therein; an optical detector (D) configured and arranged to detect light emitted from the sample when excited with said side illumination; and a casing (C) constituting an envelope into which at least the support (S) is housed and attached.
Claims
1. A hand-held microfluidic detection device, comprising: a microfluidic cell having at least one chamber intended to at least contain a sample; a support configured for the attachment thereto of said microfluidic cell; an excitation light arrangement arranged at least in part in said support to side illuminate said at least one chamber of said microfluidic cell to excite said sample contained therein; and an optical detector configured and arranged to detect light emitted from said sample when excited with said side illumination; wherein the device further comprises a casing constituting an envelope into which at least said support is housed and attached, and in that said support comprises a housing for removably attaching said microfluidic cell, wherein said microfluidic cell is a microfluidic flow cell where said at least one chamber is a channel for containing said sample flowing there within, wherein said support includes a fluidic manifold configured to fluidically communicate at least one manifold fluidic channel thereof with said at least one channel when the microfluidic flow cell is attached to the support, wherein said optical detector is configured and arranged to detect first light rays of said light emitted from said sample which depart from the sample according to one or more first emission directions going towards the optical detector, and wherein the device further comprises a parasitic light suppressing mechanism configured to avoid the impingement on the optical detector of second light rays of the light emitted from the sample or from another location of the microfluidic cell, which depart therefrom according to second emission directions opposed to sad first emission directions, or to at least attenuate the intensity of said second light rays before impinging on the optical detector, wherein the support comprises a plate with a through hole and a coupling arrangement to removably couple the microfluidic cell over said through hole, and wherein the optical detector is arranged below said through hole to receive and detect said first light rays emitted from the sample and passing through the trough hole, wherein said microfluidic cell is a microfluidic chip having a translucent plate with first and second opposite major surfaces sandwiching said at least one channel, wherein when the microfluidic chip is attached to the support said first major surface faces the optical detector, and wherein said parasitic light suppressing mechanism comprises at least a first deflection arrangement configured to deflect said second light rays once they have transmitted through said translucent plate through said second major face so that they either do not impinge on the optical detector or their intensity is attenuated before impinging on the optical detector, and wherein said first deflection arrangement comprises one or more first deflection walls arranged over said second major surface of the translucent plate of the microfluidic chip and extending perpendicularly or divergently with respect to said second major surface from first ends up to second ends.
2. The device according to claim 1, wherein said parasitic light suppressing mechanism further comprises a second deflection arrangement configured to deflect the second light rays once they have been deflected by said first deflection arrangement.
3. The device according to claim 2, wherein said second deflection arrangement comprises one or more second deflection walls extending convergently towards the second major surface of the translucent plate of the microfluidic chip from first ends, placed at a plane arranged over the second ends of the first deflection walls, up to second ends.
4. The device according to claim 3, wherein the one second deflection wall of the second deflection arrangement forms one of a cone and a convex curved cap.
5. The device according to claim 3, wherein the second deflection walls of the second deflection arrangement form a pyramid.
6. The device according to claim 3, wherein two second deflection walls of the second deflection arrangement converge, at their second ends, into a longitudinal edge.
7. The device according to claim 6, wherein a projection of said longitudinal edge on the second major surface of the translucent plate of the microfluidic chip follows a direction that is orthogonal or substantially orthogonal to a main illumination plane of said side illumination.
8. The device according to claim 7, wherein a longitudinal axis of said at least one channel of the microfluidic chip, when the microfluidic chip is attached to the support, occupies said main illumination plane.
9. The device according to claim 8, wherein the microfluidic chip comprises at least two of said at least one channel, one of them being configured and arranged so that a longitudinal axis thereof, when the microfluidic chip is attached to the support, occupies an illumination plane that is parallel to said main illumination plane and orthogonal or substantially orthogonal to said projection of said longitudinal edge.
10. The device according to claim 7, wherein said longitudinal edge belongs to a plane that is parallel or substantially parallel to the second major surface of the translucent plate of the microfluidic chip, when the microfluidic chip is attached to the support.
11. The device according to claim 3, wherein the casing comprises a top portion having a region which defines said plane at which the first ends of the one or more second deflection walls are placed.
12. The device according to claim 1, wherein the one first deflection wall of the first deflection arrangement forms a hollow truncated cone.
13. The device according to claim 1, wherein the one first deflection wall of the first deflection arrangement is one cylindrical wall that forms a hollow cylinder.
14. The device according to claim 1, wherein the first deflection walls of the first deflection arrangement form a hollow truncated pyramid.
15. The device according to claim 1, wherein the casing comprises a through opening defined at a wall thereof, wherein said through opening is configured and arranged to allow the introduction/extraction there through of the microfluidic cell with respect to the casing and the coupling/uncoupling thereof by said coupling arrangement.
16. The device according to claim 1, wherein said optical detector is also housed into said casing.
17. The device according to claim 1, further comprising an electric and electronic system operatively connected to said optical detector, to power and control the operation thereof and also to receive and process detection signals generated thereby to perform optical measurements, and connected to said excitation light arrangement, to power and control the operation thereof, and to a user interface included in the device which includes at least a user input mechanism and a display to control the operation of the device by a user and display at least graphical information related to said optical measurements.
18. The device according to claim 1, wherein the support further comprises liquid and pneumatic connectors for liquid delivery and collection to/from the at least one manifold fluidic channel, wherein said connectors are accessible from outside the casing to removably couple thereto at least one of the following components: liquid and/or gas reservoirs, external pumps, valves and actuators.
19. The device according to claim 1, wherein said excitation light arrangement comprises at least one light generating unit, wherein said light generating unit and/or an optical element directing light generated thereby is/are attached to the support such that a light beam generated by the light generating unit goes towards a respective side edge of the translucent plate of the microfluidic chip, either with an optical axis which is orthogonal to said side edge or with an optical axis which is transversal but not orthogonal to said side edge and has an emission direction away from the optical detector.
20. The device according to claim 1, further comprising a deformable sealing gasket configured and arranged to be placed, when the microfluidic chip is attached to the support, between the microfluidic chip and the support to ensure a gas-tight seal between the two.
21. The device according to claim 20, wherein said deformable sealing gasket comprises two or more O-rings interconnected through a film frame, thinner than the two or more O-rings, so that each of the two or more O-rings is configured and arranged to be positioned, when the microfluidic chip is attached to the support, in correspondence with a respective opening of the at least one channel of the microfluidic chip and a respective opening of the at least one manifold fluidic channel, wherein said film frame defines a central through-opening configured and arranged to be in correspondence with said through hole of the plate of the support.
Description
BRIEF DESCRIPTION OF THE FIGURES
(1) In the following some preferred embodiments of the invention will be described with reference to the enclosed figures. They are provided only for illustration purposes without however limiting the scope of the invention.
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DESCRIPTION OF THE PREFERRED EMBODIMENTS
(15) As shown in
(16) a microfluidic cell M, which for the illustrated embodiments is a microfluidic chip M comprising inner channels Mc (see
(17) a support S comprising a housing for removably attaching thereto the microfluidic chip M;
(18) excitation light means comprising LEDs G arranged in the support S tilted upwardly to side illuminate the inner channels Mc of the microfluidic chip M to excite the sample contained therein;
(19) an optical detector D (schematically shown in
(20) an electric and electronic system ES (schematically shown in
(21) For the embodiment shown in
(22) The support S is housed within the casing C and also attached to a structural inner element thereof, such as pillars K, for the illustrated embodiments, and, as shown in
(23) As shown, among other, in
(24) The microfluidic chip M is depicted in detail in
(25) With reference to
(26) As shown in
(27) The rest of the above mentioned light rays depicted on
(28) As already disclosed in a previous section, the device of the present invention comprises light suppressing means for avoiding the impinging of said parasitic light rays 2, 3, 4 on the optical detector D, or at least attenuating them before impinging on the optical detector D until a degree at which their negative effects become negligible.
(29) For the illustrated embodiments (see
(30) Said parasitic light suppressing means comprises a first deflection arrangement configured to deflect the second light rays 2 once they have output said translucent plate through the second major face Mb so that they either not impinge on the optical detector D or their intensity is attenuated before impinging on the optical detector D.
(31) The first deflection arrangement comprises, for the illustrated embodiments, several first deflection walls W1 (particularly four) arranged over the second major surface Mb of the translucent plate of the microfluidic chip M and extending orthogonally with respect to the second major surface Mb of the translucent from first ends W1a up to second ends W1b (see especially
(32) For most of the depicted embodiments, the first deflection walls W1 extend divergently with respect to the second major surface Mb to form a hollow truncated pyramid which encloses a volume over a portion of the second major surface Mb, the second light rays 2 departing from said portion of the second major face Mb being deflected upwards by the inner surfaces of the first deflection walls W1, as represented by the light rays 2 in
(33) Alternatively, for the embodiment illustrated in
(34) For the illustrated embodiments, the parasitic light suppressing means further comprises a second deflection arrangement configured to deflect the second light rays 2 once they have been deflected by the first deflection arrangement.
(35) As shown in
(36) The wall or walls W2 (a cross-section of which is shown in
(37) For other embodiments, the wall or walls W2 converge, at their second ends W2b, into a longitudinal edge LE, as shown in
(38) As shown in
(39)
(40) The rest of microfluidic channels Mc are arranged so that their respective longitudinal axes, or flow paths, occupy respective illumination planes that are parallel to the main illumination plane.
(41) For the embodiment of
(42) For the embodiment shown in
(43) For some embodiments, the orthogonal distance between said region of the top portion Ct defining said plane P and the major surface Mb of the translucent plate of the microfluidic chip M goes from 2 cm up to 8 cm, preferably up to 5 cm.
(44) Alternatively, for the embodiments shown in
(45) By comparing
(46) Preferably, the deflection surfaces of both the first W1 and the second W2 deflection walls are dark in order to absorb light.
(47) As shown in
(48) For another embodiment, shown in
(49) Said tubular light blocking element W3 is configured to block the impingement on the optical detector D of any possible parasitic light ray which has not been suppressed by the above mentioned parasitic light suppressing means and further parasitic light suppressing means, or that could have entered into the dark compartment enclosed by the casing C.
(50) With reference now to
(51) By releasing the retaining fingers F from a position at which they are coupled to the support S, the cup element Q pivots about articulation A up to an angular end position at which the springs Z are fully extended, as shown in
(52) By pushing the microfluidic chip M further into the housing than the situation shown in
(53) As shown in
(54) An alternative embodiment for said deformable sealing gasket J is shown in
(55) The deformable sealing gasket J of
(56) Both the support's housing and the coupling arrangement can be different to the ones illustrated for non-illustrated embodiments.
(57) Going back to
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(61) Particularly, connector Cn1 comprises a liquid and a gas port enabling the pneumatic control of liquid transfer from the manifold to the removable microfluidic chip M and the collection of liquid therefrom in a closed and gastight container R.sub.GL when attached thereto through intermediate connector combined liquid-gas connector CR.sub.GL. The gastight container R.sub.GL comprises liquid reservoir R.sub.L and gas conduct R.sub.G (for the pneumatic control of the liquid transfer), having corresponding lower output channels R.sub.Lp, R.sub.GLp through which they are communicated with the manifold channels Sc. This feature of this connector Cn1 container R.sub.GL assembly is very important in many tests to safely dispose of biological samples and reagents after use.
(62) Regarding said liquid reservoirs R.sub.L1, for example for containing reagents, they can be connected to liquid ports Cn2, Cn3, for delivery to the manifold channels Sc and finally to the microfluidic chip channels Mc.
(63) For the embodiment shown in
(64) For a non-illustrated embodiment, an external liquid valve is attached to the manifold in order to select which liquid to flow into the channels Mc of the removable microfluidic chip M from a selection of several reservoirs or input channels. In another non-illustrated embodiment, a liquid valve is embedded in the manifold. In another non-illustrated embodiment, a liquid pumping element is directly attached to or built into the manifold.
(65) In another non-illustrated embodiment, an external pneumatic valve is attached to the manifold in order to connect a gas channel Sc to a variety of other gas channels Sc that may be pressurized at different positive or negative pressures. In another non-illustrated embodiment, a pneumatic valve is embedded in the manifold. In another non-illustrated embodiment, a gas-pumping element is directly attached to or built into the manifold.
(66) In one embodiment, the light source is one light-emitting diode (LED). In another embodiment, the light sources are two LEDs placed on either side of the removable microfluidic component. In another embodiment, the light source is at least one laser. In another embodiment, the light source is at least one optical fibre. In another embodiment, the light source is a reflective coating applied to or fabricated on the surface of the fluid distribution device upon which light is projected or reflected.
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(68) Specifically, for the embodiment shown in
(69) The embodiments shown in
(70) For the embodiment shown in
(71) For the embodiment of
(72) For anon-illustrated embodiment, instead or complementarily to the above mentioned lens, another optical element is placed between the light source G and the side edge of the microfluidic chip M, such as a reflective coating arranged on a specific region of the support S.
(73) Experimental Validation:
(74) The sample contained in the microfluidic channels Mc of the microfluidic chip M may consist of one or more areas of interest. In one implementation, the sample is distributed along a two-dimensional array, with the rows being defined by the channels Mc and the columns being arbitrary determined by the deposition of reagents to limited areas. Such a sample array simplifies test multiplexing and enables high-throughput screening in a reduced area and with a reduced consumption of reagents. Imaging such an array using conventional microscopy techniques may be laborious or result in images of low quality.
(75) In the device of the present invention, a fast, compact and cost effective method has been devised to image the above mentioned array with high sensitivity thanks to the reduction in background noise provided by the light suppressing and light blocking elements integrated in the support S. Thanks to this integration, the device is capable of imaging simultaneously the entire sample area of the microfluidic consumable (2020 mm) with better signal to noise ratio than a commercial microscopy system and in a fraction of the time (approximately 0.01 vs 10 minutes). Alternative array scanning systems have been previously described, but generally they are large and expensive laboratory instruments that cannot be easily transported and used at the point of care. The developments associated to the device of the present invention have enabled to deliver a measurement system of such capability at reduced cost, weight and dimensions.
(76) The present inventors have built a prototype of the device of the present invention, and performed detection measurements on a sample, and have also performed measurements on the same sample with a laboratory microscope, in order to perform a signal-to-noise values comparison.
(77) The table below shows the results obtained, in the form of signal over noise values for signals of varying intensities. The prototype of the present invention is called therein hand-held prototype (built according to
(78) TABLE-US-00001 Signal-to-noise Signal Handheld Intensity prototype NIKON 100 5.56 2.08 80 3.88 1.93 75 3.52 1.89 65 3.03 1.65 50 2.46 1.48 30 1.55 1.23
(79) The results included in the above table prove that the device of the present invention provides such good detection results that improve not only those provided by hand-held devices but also those achieved by some commercial laboratory microscopes.
(80) A person skilled in the art could introduce changes and modifications in the embodiments described without departing from the scope of the invention as it is defined in the attached claims.