# US 10,117,990 B2 · Microfluidic intravital window

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- Number: US 10,117,990 B2
- Document ID: US10117990B2
- Status: Granted
- Kind: B2
- Application number: 15/371,493
- Filed: 2016-12-07
- Published: 2018-06-07
- Granted: 2018-11-06
- Earliest claimed: 2016-12-07
- Assignees: The Research Foundation for The State University of New York; Albert Einstein College of Medicine
- Applicants: The Research Foundation for the State University of New York; Albert Einstein College of Medicine, Inc.
- Inventors: James Castracane; Logan Butt; David Entenberg; Lauren Sfakis; John Condeelis
- Web page: https://patentgrep.com/patent/US10117990B2

## CPC

- A61M 5/14276: {specially adapted for implantation}
- A61B 5/150007: {Details}
- A61B 17/0218: {for minimally invasive surgery (A61B17/0281, A61B17/0469, A61B17/12013, A61B17/1285, A61B17/29, A61B17/320016 take precedence)}
- A61D 1/00: Surgical instruments for veterinary use
- A61D 7/00: Devices or methods for introducing solid, liquid or gaseous remedies or other materials into or onto the bodies of animals (for reproduction or fertilisation A61D19/00)
- A61M 5/172: electrical or electronic
- A61M 37/0015: {by using microneedles}
- A61M 39/24: Check- or non-return valves
- A61M 2037/0023: {Drug applicators using microneedles}
- A61M 2039/2493: {Check valve with complex design, e.g. several inlets and outlets and several check valves in one body}
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61D: VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS

## Abstract

A microfluidic intravital window includes an intravital imaging window adapted for implantation adjacent target tissue of a live animal, and a microfluidic fluid source and delivery system physically integrated into the window for controlled delivery of fluids to target tissue via the window. The microfluidic fluid source and delivery system is self-contained and completely located within the intravital imaging window, and includes at least one preloaded fluid reservoir, at least one fluid port in fluidic communication with both the at least one preloaded fluid reservoir and the target tissue, and at least one light activated fluid flow control device situated between the at least one preloaded fluid reservoir and at least one fluid port, to facilitate simultaneous in vivo viewing and remotely controlled fluid delivery to the target tissue.

## Claims

### Claim 1

A microfluidic intravital window, comprising:
an intravital imaging window adapted for implantation adjacent target tissue of a live animal; and
a microfluidic fluid source and delivery system physically integrated into the window for controlled delivery of fluid to the target tissue via the window, wherein the microfluidic fluid source and delivery system is self-contained and completely located within the intravital imaging window and includes at least one preloaded fluid reservoir, at least one fluid port in fluidic communication with both the at least one preloaded fluid reservoir and the target tissue, and at least one remotely activated fluid flow control device situated between the at least one preloaded fluid reservoir and the at least one fluid port, whereby simultaneous in vivo viewing and remotely controlled fluid delivery to the target tissue are facilitated.

### Claim 2 (depends on 1)

The microfluidic intravital window of claim 1, wherein the at least one remotely activated fluid flow control device comprises at least one light activated fluid flow control device.

### Claim 3 (depends on 2)

The microfluidic intravital window of claim 2, wherein the at least one light activated fluid flow control device includes a material having a shape that changes when irradiated with light.

### Claim 4 (depends on 3)

The microfluidic intravital window of claim 3, wherein the material has a shape that reversibly changes when alternately irradiated with light of different polarizations.

### Claim 5 (depends on 4)

The microfluidic intravital window of claim 4, wherein the material comprises an azobenzene polymer.

### Claim 6 (depends on 2)

The microfluidic intravital window of claim 2, wherein the at least one light activated fluid flow control device comprises at least one of a light activated, microfluidic: valve, pump, mixer, or dynamic fluid diverter.

### Claim 7 (depends on 6)

The microfluidic intravital window of claim 6, wherein the light activated microfluidic valve includes a surface exhibiting a topography change when irradiated with light.

### Claim 8 (depends on 7)

The microfluidic intravital window of claim 7, wherein the surface comprises a surface relief grating or a surface relief grid, with holographic light activated reversible surface patterning.

### Claim 9 (depends on 6)

The microfluidic intravital window of claim 6, wherein the light activated microfluidic pump is unidirectional, and the microfluidic fluid delivery system further includes a one-way check valve upstream and/or downstream of the light activated microfluidic pump to prevent backfill.

### Claim 10 (depends on 6)

The microfluidic intravital window of claim 6, wherein the light activated microfluidic pump comprises a reciprocal micro-pump with a light activated oscillating membrane, and is adapted to deliver fluid to the target tissue and/or extract fluid from the target tissue.

### Claim 11 (depends on 1)

The microfluidic intravital window of claim 1, wherein the intravital imaging window comprises a glass coverslip within a frame, and the frame is adapted for attachment to skin of the live animal with an inner surface of the window situated adjacent the target tissue, and the microfluidic fluid source and delivery system is completely located on the inner surface of the intravital imaging window.

### Claim 12 (depends on 11)

The microfluidic intravital window of claim 11, wherein the target tissue comprises a tumor microenvironment, and the fluid comprises a factor, drug or chemotactic agent.

### Claim 13 (depends on 1)

The microfluidic intravital window of claim 1, wherein the microfluidic fluid source and delivery system comprises a cured PDMS structure sealed to the intravital imaging window.

### Claim 14 (depends on 1)

The microfluidic intravital window of claim 1, further comprising at least one microneedle extending from an inner surface of the intravital imaging window into the target tissue to help anchor the window to the target tissue.

### Claim 15 (depends on 1)

The microfluidic intravital window of claim 1, further comprising at least one hollow microneedle in fluid communication with the at least one fluid port and extending into the target tissue to deliver the fluid at a desired depth within the target tissue.

### Claim 16 (depends on 1)

The microfluidic intravital window of claim 1, wherein the at least one fluid reservoir comprises multiple reservoirs respectively preloaded with different fluids for simultaneous and/or sequential remotely controlled delivery of the different fluids to the target tissue.

### Claim 17 (depends on 16)

The microfluidic intravital window of claim 16, wherein the at least one fluid port comprises multiple fluid ports adjacent different regions of the target tissue for simultaneous and/or sequential remotely controlled delivery of the different fluids to the different regions of the target tissue.

### Claim 18 (depends on 16)

The microfluidic intravital window of claim 16, wherein the at least one remotely activated fluid flow control device comprises a light activated fluid flow control device downstream of each reservoir.

### Claim 19 (depends on 4)

The microfluidic intravital window of claim 4, wherein the material comprises multiple parallel, spaced apart, strips of azobenzene film extending along a long axis of the film.

### Claim 20 (depends on 6)

The microfluidic intravital window of claim 6, wherein the light activated microfluidic valve includes at least one of a light sensitive cantilever element or a light sensitive diaphragm element.

### Claim 21

A microfluidic intravital window, comprising:
an intravital imaging window adapted for implantation with an inner surface of the intravital window adjacent target tissue of a live animal; and
a microfluidic fluid source and delivery system physically integrated with the window for controlled delivery of fluid to the target tissue via the window, wherein the microfluidic fluid source and delivery system is self-contained and completely located on the inner surface of the intravital imaging window and includes at least one preloaded fluid reservoir, at least one fluid port in fluidic communication with both the at least one preloaded fluid reservoir and the target tissue, and at least one light activated fluid flow control device situated between the at least one preloaded fluid reservoir and the at least one fluid port, whereby simultaneous in vivo viewing and light controlled fluid delivery to the target tissue are facilitated.
