Minimally Invasive Molecularly Imprinted Conductive Nanoneedle Sensors

Lead Research Organisation: University of Bath
Department Name: Chemical Engineering

Abstract

There has been a significant drive in recent years for the development of rapid diagnostics, specifically for sepsis, as there is a crucial time window in which patients need to be diagnosed and treated. Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The patient's immune system goes into overdrive setting off a series of reactions including widespread inflammation. Sepsis is the leading cause of death from infection, especially if not diagnosed and treated promptly. Rapid, accurate and simple tests are still lacking for sepsis. Diagnosis is an essential part of all healthcare, and sepsis is no exception, and although clinical laboratories offer sensitive, specific assays, such as blood culture and high-throughput immunoassays, they are often time and labour intensive, costly, and dependent on well-trained operators. Point-of-care diagnostics on the other hand, can offer rapid results at site, enabling informed treatments; however, these technologies are still in development. Consequently, for example, antibiotics for suspected bacterial infections can be prescribed without positive diagnosis (increasing the potential risk of antimicrobial resistance), or not prescribed at all when they are really needed (i.e. when sepsis goes undiagnosed).

The MIMIC-nano sensors will move beyond the current state-of-the-art by developing minimally invasive sensors with dense arrays of nanoneedles that can sequester and detect targeted biomarkers from interstitial fluid through the development of 'synthetic antibodies' by synthesising molecularly imprinted conductive polymers. The MIMIC-nano sensors will accurately and quickly detect biomarkers specific to inflammation from sepsis, ultimately resulting in optimised diagnosis and treatments. Bringing this need to point-of-care could transform the way patients are diagnosed and treated for antimicrobial infections in the future.
 
Title Images of Research - Bath Spa Train Station 
Description We submitted our microneedles to Images of Research competition, and cam highly commended in the Health and Wellbeing section, the images for subsequently exhibited for the public outside of Bath Spa Train Station in the city centre. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2022 
Impact We shared the potential for microneedles to be used for drug delivery purposed and also subsequently got contacted by members of the public and companies that saw the technology exhibited. 
URL https://www.bath.ac.uk/projects/images-of-research/
 
Description This work has produced an innovative way to produce a library of micro and nano needles directly from 3D printing, we have also utilising this technique for producing cheaper moulds to produce needles of a multitude of microneedle materials. The project enabled the first all polymer-based conductive microneedle device for sensing cortisol through molecularly imprinting. The project went beyond the resolution of lab-based 3D printers to produce microneedles that could painlessly penetrate skin, detecting inflammatory biomarkers which help to identify infection and utilise these platforms for controlled drug delivery of antibiotics to treat infections. The project also produce innovative nanofibre-nanoparticle molecularly imprinted polymers, which are being explore as non-invasive sweat sensors for monitoring cortisol, glucose and lactate. The work has resulted in our industry partner funding a fully-funded PhD studentship.
Exploitation Route The research has developed an exciting platform and proof-of-concept technology for utilising conductive polymers for moleculalrly imprinting and detect biomarkers directly on needle, we are now integrating as a wireless device and expanding the library of target molecules to detect in the interstitial fluid. Collaborators are taking up our microneedle designs and strategies and applying to their own research.
Sectors Healthcare

Manufacturing

including Industrial Biotechology

URL https://www.bath.ac.uk/announcements/no-more-big-needles-scientists-develop-a-skin-patch-that-painlessly-delivers-drugs-into-the-body/
 
Description Faculty Equipment Bid - Infrared system and probe
Amount £73,500 (GBP)
Organisation University of Bath 
Sector Academic/University
Country United Kingdom
Start 09/2021 
End 03/2022
 
Description University Equipment Bid Nanobioprinter
Amount £510,000 (GBP)
Organisation University of Bath 
Sector Academic/University
Country United Kingdom
Start 01/2023 
End 03/2023
 
Title Dataset for "Conductive polymer-coated 3D printed microneedles: biocompatible platforms for minimally invasive biosensing interfaces" 
Description This dataset includes all the data presented and analyzed in the aforementioned paper, "Conductive polymer-coated 3D printed microneedles: biocompatible platforms for minimally invasive biosensing interfaces". These include: CAD designs, SEM and AFM micrographs, FTIR, Raman, and EDS spectra, water sessile drop images, DMA compression tests, ex vivo skin penetration bright-field microscopy images, cyclic voltammograms, four-point probe resistivity measurements, battery-LED system photographs, and cytotoxicity assay measurements. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact Informed further research on microneedle datasets and data gathering 
URL https://researchportal.bath.ac.uk/en/datasets/dataset-for-conductive-polymer-coated-3d-printed-micro...
 
Title CROSSLINKED HYDROGEL FORMING MICRONEEDLES FOR CONTROLING THE DELIVERY OF AN ACTIVE AGENT 
Description Hydrogel-forming microneedles fabricated from 3D printed master templates were used to demonstrate their potential use for the transdermal delivery of antibiotics. Where the desired antibiotic can be encapsulated within the hydrogel's polymeric network through a room temperature swell/deswell drug loading method within minutes, eliminating the need for an external drug reservoir. The resultant impact on the mechanical properties was insignificant and successful skin penetration was observed. The hydrogel swell rate was tailored by altering the crosslinking density, as a result, the resultant drug delivery rate and dosage was manipulated for a desirable applicable delivery concentration. Measuring the antimicrobial properties highlighted the overall beneficial use of hydrogel-forming microneedles for the transdermal drug delivery of antibiotics. 
IP Reference application number: 63/364,335 
Protection Patent / Patent application
Year Protection Granted 2022
Licensed No
Impact THIS PATENT IS A PROVISIONAL APPLICATION UNDER 35 USC 111(b)
 
Title Hollow Microneedles 
Description a low force stereolithography 3D printing method was utilised for the direct production of sharp tipped HMNs. These 3D printed HMNs can penetrate skin, extract fluid and deliver drug solutions. By using a high temperature resin allows for enhancement of structural properties and an ability to withstand sterilisation processes without MN deformation occurring. Plasma treatment of these printed HMNs alters the surface chemistry for increased hydrophilicity, aiding fluid flow through the HMNs. Further coating these HMNs allows for increased biocompatibility, as well as enhancement of other properties, which can be desirable in specific applications. 
IP Reference 63/364,334 
Protection Patent / Patent application
Year Protection Granted 2022
Licensed No
Impact seeking further funding to support further developments either for licensing or spinouts.
 
Description I'm a scientist ask my anything 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We took part in the University of Bath I'm a Scientist Ask Me thing "Hi, we're Hannah and Xiang from the University of Bath. We create new materials and devices to support sustainable healthcare. Our passions include microneedles (tiny painless needles), electrospinning, mechanical energy harvesters & 3D-printing. Ask Us Anything!"
Year(s) Of Engagement Activity 2023
URL https://www.reddit.com/r/IAmA/comments/179wpdj/hi_were_hannah_and_xiang_from_the_university_of/?rdt=...
 
Description Microneedle work in the Wiley Women in Materials Science special feature for International Women's Day 2023 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Our microneedle research has been featured in the Wiley Women in Materials Science special feature 2023
Year(s) Of Engagement Activity 2023
URL https://onlinelibrary.wiley.com/doi/toc/10.1002/(ISSN)1521-4095.WomeninMaterialsScience
 
Description Press release microneedle technology 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A media announcement was published on the UoB website and a press release was sent to national and international media outlets, through Meltwater. Twitter posts appeared on both the university's main account @UniofBath and on the research account @UniofBathNews.
• Total number of articles: 108+
• Total news reach: 124M
• Details of global spread: The story appeared across 5 continents
• AVE*: US$1.1M
Year(s) Of Engagement Activity 2023
URL https://www.bath.ac.uk/announcements/no-more-big-needles-scientists-develop-a-skin-patch-that-painle...
 
Description Research highlighted in the Women in Materials Science RSC Journal for International Women's Day 2023 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Our research article was featuring in the RSC Celebrating International Women's Day: Women in Materials Science 2023. They articles are open to read to all until 8th April
Year(s) Of Engagement Activity 2023
URL https://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=mh&themeid=9022818c-728d-474f-bbee...
 
Description Salter's Institute Bath University Chemistry Festival 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact In collaboration with Salter's Institute we developed videos to share with secondary school aged children to help inspire and inform them about different areas of chemistry. They were looking for experts to be interviewed using a professional filming company, and the resulting videos will also be made available to the university for our own outreach events.
The topic Hannah Leese contributed to was "Chemical Engineering in the Real-World" and focused on the research of the materials for health lab and minimally invasive healthcare technologies.
Year(s) Of Engagement Activity 2022
 
Description Sepsis awareness month - Univeristy of Bath 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Hannah Leese was interviewed by the social media manager at the Univeristy of Bath on the research on-going for sepsis awareness month. This interviewed was shared on the University twitter feed.
Year(s) Of Engagement Activity 2021