Harnessing Non-Invasive Biomarkers for Point-of-Care Diagnostics

Point-of-care (PoC) diagnostic devices are a key enabler of convenient, cost-efficient, and accessible healthcare. These factors are a high priority for healthcare systems worldwide. 

A complementary area set to aid the evolution and expansion of PoC diagnostics is non-invasive biomarkers. Ongoing progress in this space reveals new opportunities to harness non-invasive biomarkers for earlier detection and better monitoring of disease. This is an attractive prospect. However, achieving the vision requires looking beyond biomarker assays to also consider the technicalities of collecting high-quality samples for testing. 

Benefits of Non-Invasive Biomarkers

The relative ease with which non-invasive samples can be obtained means they are well suited to diagnostic and companion diagnostic testing performed in PoC environments. Non-invasive refers to the sampling method used to obtain the biomarker, rather than its nature. Biomarkers are biological substances or factors that can be measured to indicate health status as well as the presence or potential severity of disease. Many biomarkers can be identified in blood or tissue samples obtained via invasive means, which require puncturing the skin or entering the body. Others—including chemical substances and biological components found in urine, saliva, sweat, and breath—can be collected non-invasively. 

An obvious benefit of non-invasive biomarkers for PoC diagnostics is the reduced physical impact in scenarios where invasive biomarkers are the current standard. Invasive biomarker sampling is often uncomfortable (sometimes painful) and may carry the risk of complications. For certain demographics—such as young children or the elderly—the physical and psychological impact of invasive biomarker sampling is a significant consideration. 

Since non-invasive sample collection is more straightforward and doesn’t require a clinical procedure, the diagnostic journey can also be accelerated to facilitate earlier treatment. For example, in settings such as care homes, early diagnosis of infection via analysis of biomarkers in urine could enable more timely and effective treatment interventions. 

In some cases, testing can be performed at the point of need—for instance, at home—further improving accessibility and convenience. This is especially beneficial for people in remote or underserved areas as well as those with mobility issues or chronic illness that requires regular monitoring. 

Increasing the scope of PoC diagnostic devices that use non-invasive biomarkers would be revolutionary for patients and healthcare systems alike. Here, we focus on PoC diagnostic solutions where the results are available immediately and PoC collection where testing still takes place in a central laboratory, with results returned to the patient or care giver. This is an important adjacent category as it increases access to sophisticated testing that remains impossible outside of the laboratory.

Current Developments 

Well-established examples of PoC diagnostics based on non-invasive biomarkers include urine tests for sugar levels and pregnancy. Several other interesting examples have recently been approved or are in the late stages of development. These include Healthy.io’s Minuteful Kidney, an at-home urine-based diagnostic test that assesses albumin-to-creatinine ratio to screen for chronic kidney disease (CKD). It received 510(k) clearance from the U.S. Food and Drug Administration (FDA) in 2022. Healthy.io says it allows people at risk of CKD to test from home and obtain instant clinical-grade results, regardless of their income level, location, or ethnicity. 

The FDA also granted breakthrough device designation to Viome’s Oral Health Pro with Cancer Detect in 2023. This saliva-based diagnostic test for the early detection of oral and throat cancers facilitates non-invasive sample collection via a custom device used at home or in a dental clinic. Samples are sent to a clinical laboratory for proprietary RNA sequencing to identify early biomarkers associated with oral and throat cancer. 

Other developments of note include emerging urine-based diagnostic tests offering potential for the early detection of lung cancer and breast cancer. 

A lung cancer test developed by scientists at the University of Cambridge with funding from Cancer Research UK detects “zombie cells,” which could indicate the first signs of the disease. This procedure requires the injection of a “probe” that interacts with the zombie cells and releases a smaller marker, which can be excreted in urine. While it is not non-invasive, it is less invasive and easier than a blood draw. It has been proven effective in mice, and researchers hope it will soon be trialed in humans. 

Meanwhile, Blue Box has developed a urine-based breast cancer test that outperformed mammography by 15% to 30% in proof-of-concept trials. Clinical trials are planned for 2025, with a gynecology clinic launch expected by 2026.

Technical Challenges

While there have been significant gains in the ability to use non-invasive biomarkers for health diagnoses, delivering reliable, repeatable results in real-world scenarios is not straightforward. Obtaining samples of sufficient quality for reliable diagnosis can be very difficult using non-clinical procedures. The analysis of samples can also be a challenge. 

For instance, breath samples hold great promise for the early diagnosis of lung cancer, but it can be difficult to isolate specific biomarkers from the complex mix of substances in exhaled air. Other sample types, such as saliva and sweat, can be subject to variability in the concentration of biomarkers due to factors such as the patient’s level of hydration. 

In many PoC diagnosis applications, self-collection of a sample by the patient is desirable. However, this can present additional technical challenges. Under- and over-sampling can prevent an accurate result from being obtained, and sample contamination is a major consideration. 

Some non-invasive sample types are easier to collect than others, but they can all present integrity challenges. Urine samples are a case in point. As a carrier of hormones, cells, proteins, and bacteria the body is eliminating, urine is a valuable specimen for non-invasive biomarker testing. However, the assumption it is easy to collect can be a hindrance. There is no standard device for collection beyond simple cups and funnels or tubes. Yet, obtaining a suitable, clean sample is not always straightforward and inconsistent quality is a limiting factor for PoC diagnostic tests. 

The prevalent gender data gap in healthcare is one factor at play here. Containers traditionally used for urine collection are more difficult for women to use than for men. Controlling the flow of urine to collect the right portion for the sample is also difficult for many people. This is an important consideration as some diagnostic tests, such as those for sexually transmitted infections (STIs), require “first catch”—the first 30 ml of the first morning urine—because epithelial cells and debris from the urethra are needed for analysis. 

Many of the challenges associated with sample collection could be addressed using a combination of existing, readily available technologies and empathy-led design. A human-centered mindset plays a critical role, ensuring various user needs, experiences, and scenarios are accounted for. For instance, the Peezy midstream urine collection device from Forte Medical makes it easier for women to collect urine samples, and for all people to collect midstream samples. 

It’s not just sample collection devices that benefit from a human-centric approach. Instructions for use also require attention. It’s often thought minimizing the number of user steps is beneficial, but oversimplifying instructions for use can be counterintuitive. So, rather than focusing solely on reducing the steps of sample collection, it’s important to test the steps and refine them. This facilitates development of clear instructions that maximize ease of use, reduce errors, and ensure samples meet the required standards for accurate and repeatable diagnostic testing. 

Accelerate Progress: Focus on Sample Collection

The collection of samples for PoC diagnostics holds a huge amount of untapped innovation potential. It’s often a low priority during device development, but this needs to change so progress made in non-invasive biomarker diagnostics can be leveraged in PoC settings. Companies that get this right have much to gain. Benefits could range from competitive differentiation to a quicker regulatory journey. After all, it’s easier to demonstrate the safety and effectiveness of devices when sample integrity can be ensured via robust collection methods. 

Addressing sample collection challenges from the early stages of development makes it easier to harness non-invasive biomarkers. Collaboration between assay development scientists, microfluidics engineers, biomedical engineers, and human factors specialists is key. With this combined expertise, navigating the complex interplay between accuracy, reliability, and repeatability using samples that haven’t been obtained by a clinician is more straightforward. This can expedite the market journey, ensuring non-invasive PoC diagnostic devices benefit patients and wider healthcare systems more quickly.

FURTHER READING: Spot Check—A Discussion of the In-Vitro Diagnostics Market

Nick Collier is chief technology officer at R&D consultancy Sagentia Innovation, supporting organizations as they translate new technologies from the research lab bench to commercial products. He has been responsible for numerous breakthrough products and innovations including technologies for diagnostic imaging, and in-vitro diagnostics using molecular assays, NGS, flow cytometry, and immunoassays.