Integrated organ-on-chip systems and applications of the same

• US 10,444,223 B2
• Filed: 07/30/2018
• Issued: 10/15/2019
• Est. Priority Date: 12/09/2011
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Wikswo, John P., Cliffel, David E., Markov, Dmitry A., McLean, John A., McCawley, Lisa Joy, Samson, Phillip C., Reiserer, Ronald S., Block, Frank Emmanuel, McKenzie, Jennifer Robin
• Primary Examiner(s): Forman, Betty J
• Application Number:
  US16/049,025
• Publication Number:
  US 20190064144A1
• Time in Patent Office: 442 Days
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00

Abstract

A microclinical analyzer usable for analysis of one or more bio-objects, each bio-object including an organ or a group of cells includes a fluidic network having a plurality of fluidic switches, a plurality of fluidic paths in fluid communication with the plurality of fluidic switches, and one or more on-chip pumps coupled to corresponding fluidic paths; a sensor array coupled to the fluidic network; and a microcontroller for individually controlling the plurality of fluidic switches and the one or more on-chip pumps of the fluidic network as so to operably and selectively deliver an effluent of at least one bio-object to the sensor array for detecting properties of the effluent, or to a predetermined outlet destination.

Claims

1. A microclinical analyzer usable for analysis of a plurality of bio-objects, each bio-object including an organ or a group of cells, comprising:

(a) a fluidic network having a plurality of fluidic switches, a plurality of fluidic paths in fluid communication with the plurality of fluidic switches, and one or more on-chip pumps coupled to corresponding fluidic paths, wherein the fluidic network is in fluid communication with the plurality of bio-objects and a plurality of fluids, wherein each fluidic switch comprises a rotary planar valve (RPV) and each on-chip pump comprises a rotary planar peristaltic micropump (RPPM), wherein each of the RPV and the RPPM comprises a rotary actuator, wherein the rotary actuator of the RPPM is adapted for operably pumping a fluid at a rate, and the rotary actuator of the RPV is adapted for operably rotating to selected positions to switch fluids in such a manner as to provide one or more bio-objects with selected fluids;

(b) a sensor array coupled to the fluidic network; and

(c) a microcontroller for individually controlling the plurality of fluidic switches and the one or more on-chip pumps of the fluidic network to selectively and individually perfuse at least one of the plurality of bio-objects with at least one of the plurality of fluids at a predetermined perfusion flow rate, and selectively deliver an effluent of the at least one bio-object responsive to the perfusion to the sensor array for detecting properties of the effluent, or to a predetermined outlet destination.

2. The microclinical analyzer of claim 1, wherein the microcontroller comprises at least one of a wireless communication protocol and a backup battery.

3. The microclinical analyzer of claim 1, further comprising a calibration reservoir having a plurality of containers for containing the plurality of fluids, respectively, wherein the plurality of containers is coupled to at least one of the plurality of fluidic switches and the one or more on-chip pumps for individually providing the plurality of fluids to the sensor array for calibration.

4. The microclinical analyzer of claim 1, wherein each fluidic switch comprises a valve having at least one pole and a plurality of throws, wherein the at least one pole is operably and selectively in fluid communication with one of the plurality of throws.

5. The microclinical analyzer of claim 4, wherein the plurality of fluidic switches comprises first, second, and third fluidic switches, wherein the first fluidic switch comprises a one-pole four-throw valve coupled to the calibration reservoirs, the second fluidic switch comprises a four-pole three-throw valve coupled to the first fluid switch, the sensor array and the perfusion controller, and the third fluidic switch comprises a one-pole four-throw valve coupled to the on-chip pump and outlets and another bio-object, wherein the second and third fluidic switches are coupled to each other through the on-chip pump.

6. The microclinical analyzer of claim 1, wherein the rotary actuators comprise a circular ball-bearing cage defining a plurality of spaced-apart openings thereon, and a plurality of balls accommodated in the plurality of spaced-apart openings, wherein the number of the plurality of balls is same as that of plurality of spaced-apart openings of the circular ball-bearing cage, such that each opening of the circular ball-bearing cage accommodates a respective ball, or wherein the number of the plurality of balls is less than that of plurality of spaced-apart openings of the circular ball-bearing cage, such that at least one opening accommodates no ball.

7. The microclinical analyzer of claim 6, wherein the plurality of spaced-apart openings is spaced-equally defined on the circular ball-bearing cage, wherein each two adjacent openings through the center of the circular ball-bearing cage define an angle θ

=2π

/K, K being the number of the plurality of equally spaced-apart openings.

8. The microclinical analyzer of claim 7, wherein the RPV further comprises a plurality of selectively controllable channels positioned under the actuator in relation to the plurality of equally spaced openings such that at least one selectively controllable channel is positioned under the at least one no-ball opening or under at least one no-ball location of the circular ball-bearing cage so that a fluid flow is allowed through the at least one selectively controllable channel, while the other selectively controllable channels are respectively positioned under the openings having the ball bearings so that no fluid flows are allowed through the other selectively controllable channels, wherein when rotating the actuator by a desired angle of (k×

θ

), k being 1, 2, . . . K, the at least one no-ball opening or no-ball location is selectively placed over a desired one of the selectively controllable channels.

9. The microclinical analyzer of claim 7, wherein the RPPM further comprises an input channel and an output channel positioned under the actuator in relation to the plurality of equally spaced-apart openings such that when the actuator is rotated, a fluid flow is pumped from the input channel to the output channel.

10. The microclinical analyzer of claim 1, wherein the rotary actuators comprise a wheel defining a plurality of spaced-apart sockets thereon in a circle, and a plurality of rollers accommodated in the plurality of spaced-apart sockets such that a rotation of the wheel causes the plurality of rollers to rotate along the circle.

11. The microclinical analyzer of claim 1, wherein the rotary actuators comprise a cam, and a plurality of cam-followers engaged with the cam such that a rotation of the cam causes the plurality of cam-followers to rotate along a circular path.

12. The microclinical analyzer of claim 1, wherein each of the RPV and the RPPM further comprises a motor for rotating the actuator.

13. The microclinical analyzer of claim 12, wherein the motor comprises a spring-loaded tensioning motor head or a self-tensioning motor head.

14. The microclinical analyzer of claim 1, wherein the rotary actuator of the RPPM operably pumps a fluid at a rate by actuating balls or rollers or cam-followers, and the rotary actuator of the RPV operably rotates balls or rollers or cam-followers to selected positions to switch fluids in such a manner as to provide one or more bio-objects with selected fluids.