To pierce through the skin and interact with the first biofluid available, microneedles should be mechanically strong. However, some polymers used to fabricate microneedles yield insufficient strength for the fabrication of arrays (PDMS, highly porous structures, etc.). To enhance mechanical properties, piercing materials can be used. They aim to pierce the skin evenly and dissolve quickly, clearing the way for underlying microneedles to interact with the interstitial fluid (ISF). Three materials-carboxymethyl cellulose (CMC), alginate, and hyaluronic acid (HA)-are discussed in this article. Low concentrations, for a quick dissolution while keeping enhancing effect, are used ranging from 1-5%(w/w) in deionized water. Their overall aspects, such as geometrical parameters (tip width, height, and width), piercing capabilities, and dissolution time, are measured and discussed. For breaking the skin barrier, two key parameters-a sharp tip and overall mechanical strength-are highlighted. Each material fails the piercing test at a concentration of 1%(w/w). Concentrations of 3%(w/w) and of 5%(w/w) are giving strong arrays able to pierce the skin. For the purpose of this study, HA at a concentration of 3%(w/w) results in arrays composed of microneedles with a tip width of 48 ± 8 μm and pierced through the foil with a dissolution time of less than 2 min.
In the past two decades, microneedles (MNs), as a painless and simple drug delivery system, have received increasing attention for various biomedical applications such as transdermal drug delivery, interstitial fluid (ISF) extraction, and biosensing. Among the various types of MNs, porous MNs have been recently researched owing to their distinctive and unique characteristics, where porous structures inside MNs with continuous nano- or micro-sized pores can transport drugs or biofluids by capillary action. In addition, a wide range of materials, including non-polymers and polymers, were researched and used to form the porous structures of porous MNs. Adjustable porosity by different fabrication methods enables the achievement of sufficient mechanical strength by optimising fluid flows inside MNs. Moreover, biocompatible porous MNs integrated with biosensors can offer portable detection and rapid measurement of biomarkers in a minimally invasive manner. This review focuses on several aspects of current porous MN technology, including material selection, fabrication processes, biomedical applications, primarily covering transdermal drug delivery, ISF extraction, and biosensing, along with future prospects as well as challenges.
Graphical abstract
Infectious diseases are among the leading causes of mortality worldwide. A new coronavirus named severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) was identified in Wuhan, China in 2019, and the World Health Organization (WHO) declared its outbreak, coronavirus disease 2019 (COVID-19), as a global pandemic in 2020. COVID-19 can spread quickly from person to person. One of the most challenging issues is to identify the infected individuals and prevent potential spread of SARS-CoV-2. Recently, anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody tests using immunochromatographic methods have been used as a complement to current detection methods and have provided information of the approximate course of COVID-19 infection. However, blood sampling causes pain and poses risks of infection at the needle puncture site. In this study, a novel patch sensor integrating porous microneedles and an immunochromatographic assay (PMNIA) was developed for the rapid detection of anti-SARS-CoV-2 IgM/IgG in dermal interstitial fluid (ISF), which is a rich source of protein biomarkers, such as antibodies. Biodegradable porous microneedles (MNs) made of polylactic acid were fabricated to extract ISF from human skin by capillary effect. The extracted ISF was vertically transported and flowed into the affixed immunoassay biosensor, where specific antibodies could be detected colorimetrically on-site. Anti-SARS-CoV-2 IgM/IgG antibodies were simultaneously detected within 3 min in vitro. Moreover, the limit of detection of anti-SARS-CoV-2 IgM and IgG concentrations was as low as 3 and 7 ng/mL, respectively. The developed device integrating porous MNs and immunochromatographic biosensors is expected to enable minimally invasive, simple, and rapid anti-SARS-CoV-2 IgM/IgG antibody testing. Furthermore, the compact size of the MN and biosensor-integrated device is advantageous for its widespread use. The proposed device has great potential for rapid screening of various infectious diseases in addition to COVID-19 as an effective complementary method with other diagnostic tests.
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