# US 11,078,453 B2 · Nanoneedles for intracellular applications

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- Number: US 11,078,453 B2
- Document ID: US11078453B2
- Status: Granted
- Kind: B2
- Application number: 16/066,724
- Filed: 2017-01-03
- Published: 2018-12-13
- Granted: 2021-08-03
- Earliest claimed: 2016-01-04
- Assignees: King Abdullah University of Science and Technology
- Applicants: King Abdullah University of Science and Technology
- Inventors: Jürgen Kosel; Mincho Nikolaev Kavaldzhiev; Jose Efrain Perez
- Web page: https://patentgrep.com/patent/US11078453B2

## CPC

- C12M 1/26: Inoculator or sampler
- A61B 5/685: {Microneedles}
- A61B 10/0045: {Devices for taking samples of body liquids}
- A61B 10/0233: {Pointed or sharp biopsy instruments}
- A61M 37/0015: {by using microneedles}
- B81B 1/008: {Microtips}
- B81C 1/00111: {Tips, pillars, i.e. raised structures (microneedles A61M37/0015)}
- C12M 23/20: {Material Coatings (immunocoatings C12M25/00)}
- A61B 2010/0225: {for taking multiple samples}
- A61M 2037/0023: {Drug applicators using microneedles}
- A61M 2037/003: {having a lumen}
- A61M 2037/0053: {Methods for producing microneedles}
- B81B 2201/055: Microneedles
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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)}
- B81B: MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES (piezoelectric, electrostrictive or magnetostrictive elements per se H10N30/00, H10N35/00)
- B81C: PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS (making microcapsules or microballoons B01J13/02; processes or apparatus specially adapted for the manufacture or treatment of piezoelectric, electrostrictive or magnetostrictive elements per se H10N30/01)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Nanoneedles and nanoneedle arrays and methods of making nanoneedles are provided. The methods can include multilayer fabrication methods using a negative photoresist and/or a positive photoresist. The nanoneedle arrays include one or more nanoneedles attached to a surface of a substrate. The nanoneedle can have both a proximal opening and a distal opening, and an inner passageway connecting the proximal opening and the distal opening. The nanoneedle can have a functional coating. The nanoneedle can include iron, cobalt, nickel, gold, and oxides and alloys thereof. The nanoneedle arrays can be used for the administration and/or the extraction of agents from individual cells. In one or more aspects, the nanoneedles can be magnetic nanoneedles. An oscillating magnetic field applied to a magnetic nanoneedle can induce one or both of heating and vibration of the magnetic nanoneedle. The heating and/or vibration can cause a magnetic nanoneedle to penetrate the wall of a cell.

## Claims

### Claim 1

A method of fabricating a nanoneedle array, the method comprising the steps of:
depositing a thin-film of a conductive metal layer onto an upper surface of a substrate;
patterning a negative photoresist layer onto the conductive metal layer;
electroplating a material onto the conductive metal layer using the patterned negative photoresist layer to form the nanoneedle having an inner passageway;
etching of the conductive metal layer to expose part of the upper surface of the substrate; and
etching partially the bottom surface of the substrate to form a proximal opening to the inner passageway,
wherein a first portion of the nanoneedle, proximal to the substrate, includes the conductive metal layer, and a second portion of the nanoneedle, distal from the substrate, includes the electroplated material.

### Claim 2 (depends on 1)

The method of claim 1, further comprising patterning a second photoresist layer onto the bottom surface of the substrate prior to the etching of the bottom surface of the substrate;
wherein the etching of the bottom surface of the substrate forms a channel from the patterned second photoresist layer.

### Claim 3 (depends on 1)

The method of claim 1, further comprising:
depositing a thin protective layer on the substrate, around the nanoneedle.

### Claim 4 (depends on 1)

The method of claim 1, wherein the substrate comprises a silicon substrate or a glass substrate.

### Claim 5 (depends on 1)

The method of claim 1, wherein the nanoneedle comprises a material selected from the group consisting of iron, cobalt, nickel, gold, and oxides and alloys thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein the nanoneedle has a width of about 100 nm to 1000 nm.

### Claim 7 (depends on 1)

The method of claim 1, wherein the nanoneedle has an aspect ratio of about 3 to 10.

### Claim 8 (depends on 1)

The method of claim 1, wherein the nanoneedle array is a magnetic nanoneedle array.