As we observe Cystic Fibrosis Awareness Month this year, there are many reasons for optimism in the field. In this 2-part series, we explore the latest treatment updates and exciting developments in cystic fibrosis. To read more, visit Part 1.

Optimizing outcomes for patients with cystic fibrosis (CF) depends on early diagnosis and treatment initiation. However, conventional methods for sweat collection and analysis “can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production,” wrote the authors of research published in March 2021 in Science Translational Medicine.1

To address this issue, the researchers developed a soft, microfluidic “sweat sticker” that simplifies the process, increases comfort for infants being tested, and allows for analysis using a smartphone camera.1 Results of clinical validation studies have demonstrated clinical equivalence in the accuracy of the sweat sticker compared with existing methods, along with reduced leakage rates.


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We interviewed several of the study authors to learn more about this emerging technology:

Roozbeh Ghaffari, PhD, research associate professor in the Department of Biomedical Engineering and director of translational research at the Querrey Simpson Institute for Bioelectronics at Northwestern University in Chicago, Illinois, and cofounder and CEO of Epicore Biosystems, Inc.

Tyler Ray, PhD, assistant professor in the Department of Mechanical Engineering  at the University of Hawai’i at Mānoa in Honolulu, Hawaii. 

Cystic fibrosis researcher Susanna A. McColley, MD, scientific director of interdisciplinary research partnerships and professor of pediatrics in pulmonary and sleep medicine at the Feinberg School of Medicine at Northwestern University.

What inspired the idea for the development of the sweat sticker?

Dr Ray: In the fall of 2016, the Rogers Group’s [John A. Rogers] paper describing the first epidermal microfluidic (epifluidic) device was published in Science Translational Medicine.2 My background is in microfluidic lab-on-chip devices, so having just recently joined the group a few months prior as one of the first Northwestern University postdoctoral fellows , I was eager to work on a project in this area. 

Shortly after the paper came out, Shannon Haymond, PhD, who was director of Clinical Chemistry for the Ann & Robert H. Lurie Children’s Hospital at the time, contacted John, as it seemed this platform could address some of the problems frequently encountered in pediatric clinical chemistry when newborns need diagnostic testing for CF. Limitations with the currently used (and FDA-cleared) collection devices were resulting in an unacceptable number of failures due to too little sweat being collected, typically because of the poor fit/seal of the rigid collection devices on small infant arms and legs. 

These problems were being widely experienced by labs using those devices, including at Lurie Children’s, and were often the focus of quality improvement efforts. This is because failed collections result in delayed results and potentially, diagnoses, with additional burden and anxiety for families. Clinical sweat collection has traditionally been a highly specialized procedure with tight quality standards set and monitored by the Cystic Fibrosis Foundation

After meeting with Shannon and learning more about these collection challenges, I thought that the soft, flexible sweat collection platform would simplify the process and improve the success of collection. Although initial prototypes were tested shortly after, the final embodiment of the sweat sticker that we used in the pilot study required a significant amount of development. In particular, the idea to integrate fun graphical elements to make it more sticker-like came from my work with the National Kidney Foundation for SXSW in 2017 to adapt tattoo-inspired artwork into similar devices for monitoring hydration.3

This established the foundation for adding images without changing the soft, flexible nature of the device. This was an important aspect of the device for both improving the testing experience for kids and for enabling an improved method to measure chloride levels on the device using a smartphone. The accuracy of our approach is comparable to the clinical standard in our limited study, which we plan to validate further in an expanded study.

Dr Ghaffari: The sweat sticker builds on our group’s foundational research in soft wearable electronics and microfluidics. In studying various biofluids, we realized that there is an enormous amount of information locked away in a single droplet of sweat that would otherwise be wiped away with a towel and thrown in the laundry basket. 

The sweat sticker allows us to noninvasively capture, analyze, and learn about an individual’s underlying biochemical and metabolic health in ways that were previously only possible in advanced laboratory settings with expensive diagnostic equipment. 

These insights from the sweat sticker are applicable in the home and in remote settings and are particularly relevant to CF research and diagnostics, whereby sweat samples are regularly analyzed for chloride levels.

What is the anticipated impact of this approach on the landscape of CF diagnosis and treatment?

Dr McColley: Since 2010, all US states have had newborn screening for CF.4 After a positive newborn screening test, a sweat test is needed to confirm diagnosis. Approximately 10% to 20% of infants will produce insufficient sweat, meaning that the diagnosis cannot be confirmed or excluded.5 A small device that requires less sweat has high potential to overcome this problem. The colorimetric system has potential to allow sweat testing closer to where families live, as laboratory chloridometry may not be needed. In some states, families have to drive for hours with small babies to get a sweat test.1

There is also significant need in low- and middle-income countries, and the Cystic Fibrosis Foundation is working with stakeholders to support appropriate diagnosis and care in these countries. Sweat testing is critical in this endeavor,  and again, a smaller and easier-to-use device can bridge this gap.  

A decrease in sweat chloride is a very sensitive marker for CFTR function. In CF drug development, a reduction in sweat chloride is an important biomarker and is strongly predictive of drug efficacy in populations, though less so in individuals. This device would represent an advance in conducting clinical trials since it is much less cumbersome than the current standard.

When is this expected to be available for routine clinical use, and what are next steps toward this goal?

Dr Ray: Although it’s a long path towards clinical adoption and routine clinical use, other members of the group have either successfully brought devices to market or are in the process of doing so. For us, our next step is to conduct a larger multicenter trial of the sweat sticker so we can further evaluate performance on infant populations. We also plan to continue development and validation of our integrated chloride measurement capabilities. With these expanded capabilities, we envision that the sweat sticker could someday be used as a method for patients with CF to track their symptoms during daily living.

To summarize, we’re certainly interested in pushing this to clinical use as a one-time diagnostic; however, we need to do much larger clinical studies focused on collection: Can this decrease instances of QNS (quantity not sufficient) compared with current methods? Macroduct just released the “Advanced” version [a sweat induction and collection method], so we would also need to test against that.6

We also need to expand the clinical study of the silver chloranilate in terms of accuracy and performance, as all of the work has been focused on athletics, such as the Epicore Biosystems’ Gatorade Gx Sweat Patch.7

Dr Ghaffari: The sweat sticker is currently in development with several clinical studies underway. Epicore Biosystems, a spinout company from the Querrey Simpson Institute for Bioelectronics at Northwestern University, is leading the commercialization and regulatory submission efforts for this new wearable technology.

Are there any additional details you would like to mention about the sweat sticker?

Dr Ray:  The study used the same sweat stimulation system that is currently used by the diagnostic test. This is typically performed by a phlebotomist (in routine testing).

The colorimetric assay reacts with chloride to release a color marker. This creates a quantitative color response that is directly proportional to the concentration of chloride in sweat. The standard deviation of our colorimetric method is approximately 1 mM, which is similar in accuracy to the clinical testing method. (The equipment is termed a chloridometer and the method is coulometry.) We reported 0% instances of QNS in our pilot study for the sweat sticker.  This is a very exciting result.1

Dr McColley: As a pediatrician, it is important to note that the children in this study had a strong preference for the sticker over the standard collection device.Anything we can do to make children more comfortable and happy is important, especially in health care settings.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

References

  1. Ray TR, Ivanovic M, Curtis PM, et al. Soft, skin-interfaced sweat stickers for cystic fibrosis diagnosis and management. Sci Transl Med. 2021;13(587):eabd8109. doi:10.1126/scitranslmed.abd8109
  1. Koh A, Kang D, Xue Y, et al. A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat. Sci Transl Med. 2016;8(366):366ra165. doi:10.1126/scitranslmed.aaf2593
  1. National Kidney Foundation. Tech tattoos. Accessed online May 6, 2021.
  1. Cystic Fibrosis Foundation. All fifty states to screen newborns for cystic fibrosis by 2010. Last updated July 7, 2009. Accessed May 20, 2021. https://www.cff.org/About-Us/Media-Center/Press-Releases/All-Fifty-States-to-Screen-Newborns-for-Cystic-Fibrosis-by-2010/
  1. LeGyrs VA, McColley SA, Li Z, Farrell PM. The need for quality improvement in sweat testing infants after newborn screening for cystic fibrosis. J Pediatr. 2010;157(6):1035-1037.  
  1. ELITechGroup. ELITechGroup Biomedical Systems announces the release of the Macroduct® Advanced – a sweat induction and collection method cleared by the FDA. Published August 20, 2018. Accessed May 20, 2021. https://www.elitechgroup.com/north-america/news/elitechgroup-biomedical-systems-announces-the-release-of-the-macroduct-advanced-a-sweat-induction-and-collection-method-cleared-by-the-fda/
  1. Epicore Biosystems. Epicore Biosystems launches the Gx Sweat Patch in partnership with Gatorade and PepsiCo. March 20, 2021. Accessed May 6, 2021. http://www.epicorebiosystems.com/gx-sweat-patch/