Successful development of a point-of-care HPV screening tool

The aim of the EU-funded ELEVATE project was the development and validation of a cervical cancer screening tool that can yield rapid, easy-to-understand results at low costs. Alongside a multinational team of partners who carried out the research, Labman’s role as the integration technical partner was to develop the device which could reliably actuate a complex microfluidic cartridge.

Despite multiples challenges, the completed device has proven to consistently execute the assays through precise control of liquids on a microfluidic scale. Owing to its portable nature, support of patient self-sampling and rapid reading of results, the device is set to drastically improve pathways into the healthcare system for thousands of hard-to-reach communities of women across the globe.

Preventative screening for hard-to-reach populations.

Cervical cancer is the fourth most common cancer in women, and the hard-to-reach populations in many countries are at a higher risk of developing the disease. Preventive screening programmes and vaccination against human papillomavirus (HPV) result in reduced cancer incidence and mortality.

The overall goal of the project was to enhance screening coverage for cervical cancer, particularly for hard-to-reach women, either geographically, culturally or both. The point-of-care detection device is designed to identify HPV infections and biomarkers indicating cancer development, in women from different ethno-geographic origins and socioeconomic classes.

Woman in a third world community carrying shopping bags

Compact and portable

The solution is a portable, point-of-care HPV testing device that yields rapid, easy-to-understand results, without relying on trained medical personnel. The device is capable of completely automated detection of 14 HPV strains and 2 proteomic biomarkers, with the only end-user intervention being introduction of the self-sample swab. Able to obtain a patients’ result ‘while-you-wait’ the device provides quantitative information of each of the HPV strains and the proteins.

Compatible with self-sampling

For many women worldwide, cervical cancer screening is a time consuming and stressful event; it requires a visit to a health centre and a gynaecological examination, i.e. taking a cervical smear. This approach also requires trained professionals and lab equipment, which are often unavailable in resource limited countries. A more accessible test based on self-sampling could increase cervical cancer screening in isolated populations or low-income countries, but also among women in general who for a variety of reasons do not engage with screening programmes.

Comprehensive virus detection

Use of HPV DNA tests as screening strategies is limited by their low specificity to detect transforming infections with high risk to drive pre-cancer and cancer. This might be even more pronounced when testing women from different ethno-geographic origins because specific HPV variants are associated with different patient origins. The device will sequence the DNA of 14 high risk HPV types and verify the genomic variation.

Identifying cancer progression

The simultaneous detection of HPV DNA with two proteomic biomarkers will allow for more accurate detection of HPV infections associated with cervical cancer progression. Positive cases for both tests (genomic and proteomic) would be considered high-risk cases for cancer development and those patients would be referred on for further examination and potentially treatment.

The challenge of microfluidics

Microfluidics historically have numerous obstacles in biomedical applications, particularly for diagnostic devices where subtle interactions can result in an inaccurate assessment.

ELEVATE consortium partners at University of Rovira i Virgili and University of Ghent conceptualised and developed the novel assay that enables the combined detection of 14 oncogenic HPV DNA and the expression of two cervical cancer protein biomarkers. This assay comprises various steps involving complex biochemical reactions.

Consortium partner Fraunhofer IMM translated the assay steps into a complex microfluidic network. The network comprises sample collection ports, microfluidic channels, blisters/capsules filled with sensitive freeze-dried and liquid reagents, gold-electrode array and waste collection chambers. The microfluidic network design was then optimised for production in higher volumes by another consortium partner at microLIQUID (now TE Connectivity). The entire cartridge is no bigger than the palm of your hand.

The handling, positioning, and precise flushing of many liquids inside the channels of the cartridge was extremely demanding. Rainer Gransee, IMM, worked alongside his team of biologists and engineers to develop the cartridge design.

"It was only possible through the implementation of Labman’s sophisticated optical plug flow detection using an integrated camera in combination with clever software for precisely controlling pumps and valves. This allowed the subsequent flushing, mixing, incubation, washing and the final read-out of the analytes to be detected."

Rainer GranseeIMM Fraunhofer

Microfluidic lab-on-a-chip for ELEVATE project

Ground breaking results

ICREA Research Professor, Ciara O’Sullivan has been working with biosensors for 30 years and microsystems for over 20. She established the Nanobiotechnology and Bioanalysis Group at the Universitat Rovira i Virgili, and worked on developing the assay. Ciara spoke about the high level of precision needed for the microsystem and the instrumentation to work together, to successfully complete the assay.

"Microsystems, they all have the same objective, sample in, result out. I’ve never seen any single system work. Most of the time, either you get the fluids just flying through the system and there’s no control, so there’s no proper mixing or measurement. Or, the liquid stops halfway through because there isn’t enough force to propel the liquid through the microsystem. The success is totally dependent on the design of the microsystem and the design of the instrumentation."

"What Labman have done, they’ve developed this instrumentation that truly makes everything automated – I’ve seen it again and again, it literally is sample in, result out. I’ve worked together with many, many companies over the years and while there has been some successes, no one has been able to achieve this."

"The detection part of the technology is quite complex, its electrochemical detection. Labman have developed this really fantastic potentiostat that is able to measure 64 different markers within 6 seconds. That doesn’t exist. There is no other potentiostat on the market that can do that. It’s more than impressive."

Ciara O'SullivanICREA Research Professor

Portable medical device with a microfluidic chip.

What’s next for ELEVATE?

85% of women who will die from cervical cancer (which is an entirely preventable disease) will be from the developing world. ELEVATE is undergoing clinical trials, to test the technology with samples from real patients and validate the results using existing laboratory methods.

These positive developments could lead to a real improvement for the detection of HPV infections, improving the healthcare system and ultimately saving lives of thousands of women. The successful development of the device is testament to the remarkable synergy between multinational partners.

"Collaboration within the consortium was amazing, especially with all technical partners, taking into account the highly specialised expertise of each partner. These reach from electrochemistry, to microfluidics, to mechanical design, automation and manufacturing knowhow making it necessary to find the right terms and to think alike with the project success in mind. There was a huge commitment being necessary, especially shown by Labman responsible for “knitting” all the parts together in the end."