Granted Patent B2

US 12,263,483 · App. 18/416,693 · Granted Apr 1, 2025

Inventors: Mais J. Jebrail (Toronto, CA); Ronald Francis Renzi (Tracy, CA); Steven Branda (Livermore, CA)

Assignee: INTEGRA Biosciences AG

B01L3/502784B01L3/502715B01L3/502792B01L7/525B01L2200/142B01L2200/143B01L2200/16B01L2300/0867B01L2300/1805B01L2300/1822B01L2400/0427

Abstract

Claims (38)

1. A microfluidic apparatus configured to replenish a reaction droplet to correct for evaporation, the apparatus comprising:

a first hydrophobic layer;

a second hydrophobic layer;

an air gap formed between the first hydrophobic layer and the second hydrophobic layer;

a sensor configured to detect a volume of the reaction droplet within the air gap; and

a controller in communication with the sensor and configured to move a replenishing droplet so as to combine the replenishing droplet with the reaction droplet when the detected change in the volume of the reaction droplet falls below a threshold value.

2. The apparatus of claim 1 , further comprising a thermal regulator, wherein the thermal regulator is configured to form a thermal zone in the air gap comprising a plurality of adjacent unit cells, further wherein the thermal regulator is configured to heat and/or cool the reaction droplet within the thermal zone.

3. The apparatus of claim 2 , wherein the controller is configured to adjust a temperature of the replenishing droplet within the thermal zone to match a temperature of the reaction droplet.

4. The apparatus of claim 1 , wherein the first hydrophobic layer is disposed on a first plate and the second hydrophobic layer is disposed on a second plate.

5. The apparatus of claim 1 , wherein the sensor comprises an optical sensor.

6. The apparatus of claim 1 , wherein the sensor is configured to detect an electrical property between one or more actuation electrodes and one or more ground electrodes.

7. The apparatus of claim 1 , wherein the controller is configured to detect a change in the volume of the reaction droplet based on input from the sensor.

8. The apparatus of claim 1 , wherein the controller is configured to combine the replenishing droplet with the reaction droplet by moving the replenishing droplet, the reaction droplet or the replenishing droplet and the reaction droplet within the air gap.

9. The apparatus of claim 1 , further comprising an aperture through one of the two hydrophobic layers forming the air gap, wherein the aperture is configured to connect to a source of solvent and to form the replenishing droplet.

10. A microfluidic apparatus comprising:

a first plate comprising a first hydrophobic layer;

a second plate comprising a second hydrophobic layer;

an air gap formed between the first hydrophobic layer and the second hydrophobic layer;

a sensor configured to detect a change in an optical intensity of a reaction droplet within the air gap;

a controller configured to:

determine when a volume of the reaction droplet falls below a threshold based on the change in the optical intensity, wherein the reaction droplet comprises a solvent and reaction reagents;

introduce a replenishing droplet into the air gap of the microfluidic apparatus, wherein the replenishing droplet comprises a solvent; and

combine the replenishing droplet with the reaction droplet after the volume of the reaction droplet falls beneath the threshold.

11. The apparatus of claim 10 , wherein the threshold of a change in volume of the reaction droplet is a change of 30% or more.

12. The apparatus of claim 10 , further comprising a thermal regulator configured to heat the reaction droplet, the replenishment droplet, or a combination thereof, in a thermal zone of the air gap of the microfluidic apparatus.

13. The apparatus of claim 10 , the replenishing droplet has a volume of between 10% and 50% the volume of the reaction droplet.

14. The apparatus of claim 10 , wherein the controller is further configured to move the replenishing droplet, the reaction droplet, or both the replenishing droplet and the reaction droplet and thereby combine the replenishing droplet and the reaction droplet.

15. The apparatus of claim 10 , wherein the controller is further configured to combine the replenishing droplet with the reaction droplet by moving the replenishing droplet, the reaction droplet, or both the replenishing droplet and the reaction droplet.

16. The apparatus of claim 10 , wherein the controller is configured to determine a change in optical intensity based on an increase in colorimetric intensity of the reaction droplet.

17. A microfluidic apparatus configured to replenish in a reaction droplet to correct for evaporation within an air gap formed between a pair of hydrophobic layers, the apparatus comprising:

a camera configured to monitor a size of a reaction droplet in the air gap; and

a controller coupled to the camera and configured to:

determine when the size of the reaction droplet falls below a threshold, wherein the reaction droplet comprises a solvent and reaction reagents;

introduce a replenishing droplet into the air gap of the microfluidic apparatus, wherein the replenishing droplet consists of solvent; and

move the replenishing droplet to combine the replenishing droplet with the reaction droplet after the size of the reaction droplet falls below the threshold.

18. The apparatus of claim 17 , wherein the threshold of a change in size of the reaction droplet is a change of 30% or more.

19. The apparatus of claim 17 , further comprising a thermal regulator configured to heat the reaction droplet, the replenishment droplet, or a combination thereof, in a thermal zone of the air gap of the microfluidic apparatus.

20. The apparatus of claim 17 , wherein the replenishing droplet has a volume of between 10% and 50% the volume of the reaction droplet.

Assignments (1)

Continuity (5)

References Cited (400)