The_20Scientist_20March_202019 (1)

03.2019 | THE SCIENTIST 23

MODUS OPERANDI

© GEORGE RETSECK

T

he progression of an immune

response can be thoroughly studied

in the blood thanks to the ease of

drawing the fluid from animals and humans.

But “it’s becoming increasingly clear that

tissue-level responses don’t look like blood-

level responses,” says immunologist Sarah

Fortune of the Harvard T.H. Chan School

of Public Health. “And we haven’t had very

good ways to monitor tissue responses.”

A researcher could examine an immune

response in, for example, the skin by taking

a punch biopsy, which is invasive, or by

measuring redness and swelling, which

reveals nothing about the cells and factors

involved in the response.

But new microneedle patches devised

by MIT’s Darrell Irvine and colleagues

provide information about the cellular

response without having to remove tissue

for analysis.

The patches measure approximately 1

cm^2 , contain an array of roughly 80 solid

polymer microneedles (each one around

250 μm^2 at its base and 500–600 μm

long), and are coated in a biocompatible

dried hydrogel. When applied to the skin,

the needles puncture the epidermis, the

hydrogel swells as it contacts fluids in

the tissue, and immune cells can migrate

inside. While the gel can be used as is,

the team found that including nonspecific

immune-boosting agents (adjuvants)

increased cell recruitment twofold. Specific

antigens can also be included to assess

different immune dynamics, such as the

development of antigen-targeted cells

following a vaccination.

The team used such adjuvant- and

antigen-loaded microneedle patches to

analyze skin-resident memory T cells in

mice after vaccination with an immunogenic

protein. They found that while both the skin

and blood had an abundance of these cells

in the early weeks following vaccination,

after a few months their numbers had

dwindled in the blood but remained high in

the skin—possibly because the skin is a first

line of defense, says Irvine.

Fortune, who was not involved in the

study, says the patches are “an extremely

useful immune monitoring technology

that opens up new opportunities for

understanding tissue-level responses to

infection and vaccination.” (Sci Transl Med,

10:eaar2227, 2018) g

A microneedle-containing skin patch offers researchers a noninvasive

way to survey immune responses in mice.

BY RUTH WILLIAMS

Stick-On Immune Cell Monitor

SKIN IMMUNE

CELL MONITORING

Biopsy

Microneedle patch

PROCEDURE

A small section of epidermis with underlying dermis is

removed with a metal punch

The patch is pressed onto the skin and held in place

for 24 hours with medical tape. The hydrogel-coated

microneedles puncture the epidermis and upper der-

mis and immune cells migrate into the gel.

IMMUNE CELL ANALYSIS

Histological techniques, such as cell staining

with labeled antibodies or flow cytometry

Flow cytometry of cells extracted from the

dissolved hydrogel

INVASIVE?

Ye s

Minimally

APPROVED FOR

USE IN HUMANS?

Ye s

No

AT A GLANCE

Microneedle

patch

PATCHWORK IMMUNE MONITORING: To monitor an animal’s immune response to a given

stimulus, researchers can apply a stick-on patch, containing polymer microneedles coated with

a dried hydrogel, to the skin, puncturing the epidermis. The hydrogel swells upon contact with

fluids in the tissue, and skin-resident immune cells can migrate into it. Immunogenic molecules

and antigens incorporated into the gel help to attract and retain immune cells either specifically

(via antigen recognition) or nonspecifically (via innate pathways). After 24 hours, removal of the

patch and processing of the hydrogel enables recovery of the cells for further analysis.

Hydrogel

swells and cells

move in Patch is removed and cells extracted

Microneedle with

dried hydrogel