Systems and methods for integration of microfluidic tear collection and lateral flow analysis of analytes of interest
Systems, methods, and devices for analyzing small volumes of fluidic samples, as a non-limiting example, less than twenty microliters are provided. The devices are configured to make a first sample reading, for example, measure an energy property of the fluid sample, for example, osmolality, make a second sample reading, for example, detecting the presence or concentration of one or more analytes in the fluid sample, or make both the first sample reading and the second sample reading, for example, measuring the energy property of the fluid sample as well as detecting the presence or concentration of one or more analytes in the fluid sample.
1. A device for analyzing a fluidic sample, the device comprising:
(a) a fluid inlet;
(b) a first sample region in fluid communication with the fluid inlet, wherein the first sample region comprises at least one transducer configured to detect an energy property of the fluidic sample and generate a first sample reading, wherein the first sample reading is indicative of osmolarity of the fluidic sample;
(c) a second sample region in fluidic communication with the first sample region and shaped to receive a volume of 10 nL to 500 nL of the fluidic sample, the second sample region comprising a detection substrate configured to permit detection of one or more analytes in the volume of the fluidic sample to generate a second sample reading;
(d) a first valve disposed between the first sample region and the second sample region, wherein the first valve controls fluid flow between the first sample region and the second sample region, wherein at least a portion of the detection substrate is positioned substantially into a first end of the first valve and spaced apart from the first sample region;
(e) a fluid reservoir disposed within the device and in fluidic communication with the second sample region, the fluid reservoir containing a transfer fluid, which when transferred to the second sample region is capable of hydrating a reagent disposed within the second sample region, washing the detection substrate during operation of the device, or both; and
(f) a second valve disposed between the fluid reservoir and the second sample region.
2. The device of claim 1 , wherein the detection substrate comprises a microporous substrate comprising one or more serpentine channels that act as a fluidic delay and a path for sample transfer, and, during operation, at least a portion of the volume traverses the microporous substrate.
3. The device of claim 1 , wherein the detection substrate comprises a microporous substrate having one or more flow control structures to adjust a direction of flow of the volume of fluidic sample as it traverses the second sample region.
4. The device of claim 2 , wherein the microporous substrate comprises a plurality of apertures to facilitate a substantially uniform fluid front.
5. The device of claim 1 , wherein the detection substrate further comprises an immobilized first binder capable of binding, either directly or indirectly, the one or more analytes if present in the volume.
6. The device of claim 5 , wherein the detection substrate further comprises a second binder capable of binding the one or more analytes if present in the volume, wherein the second binder optionally is conjugated with a detectable moiety.
7. The device of claim 1 , wherein the fluid inlet is adjacent and oriented perpendicular to a flow of the fluidic sample from a sample tip shaped to receive a volume of the fluidic sample.
8. The device of claim 1 , wherein the reservoir is disposed on a carrier comprising a microfluidic reservoir to delay flow or trap bubbles.
9. The device of claim 1 , wherein the first sample region and the second sample region are fluidically coupled via a through-hole or passage.
10. The device of claim 2 , wherein the microporous substrate further comprises overflow channels adjacent to the valve.
11. The device of claim 2 , wherein the microporous substrate further comprises shorter path length rehydration channels.
12. The device of claim 11 , wherein the shorter path length rehydration channels surround a central path for sample transfer.
13. The device of claim 1 , wherein the fluid reservoir is partitioned to hold more than one of a transfer buffer, wash fluid, transfer fluid, sample fluid, gas, or air.
14. The device of claim 1 , further comprising a plunger that creates an air pulse to push the volume past the first valve.
15. The device of claim 1 , wherein the energy property of the fluidic sample is an impedance of the fluidic sample.
16. The device of claim 1 , wherein the at least a portion of the detection substrate comprises a tongue configuration that descends into the first end of the first valve.
17. The device of claim 1 , wherein the at least a portion of the detection substrate descends from the second sample region into the first end of the first valve.
18. The device of claim 1 , further comprising a plurality of electrodes disposed within and/or adjacent to the first sample region and configured to determine when a prescribed amount of volume of the fluid sample is collected within the first sample region.
19. The device of claim 1 , wherein the second valve is disposed between the fluid reservoir and the first sample region.
20. The device of claim 1 , wherein the first valve is oriented perpendicular to a flow of the fluidic sample from the first sample region.