Sweat Diagnostics
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Sweat diagnostics is an emerging non-invasive technique used to provide insights to the health of the human body. Common
sweat Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distribut ...
diagnostic tests include testing for
cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
and
illicit drugs The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent the recreational use of certain intoxicating substances. While some drugs are illegal to possess, many governments regulate the ...
. Most testing of human sweat is in reference to the
eccrine sweat gland Eccrine sweat glands (; from Greek ''ekkrinein'' 'secrete'; sometimes called merocrine glands) are the major sweat glands of the human body, found in virtually all skin, with the highest density in palm and soles, then on the head, but much less ...
which in contrast to the
apocrine sweat gland An apocrine sweat gland (; from Greek ''apo'' 'away' and ''krinein'' 'to separate') is composed of a coiled secretory portion located at the junction of the dermis and subcutaneous fat, from which a straight portion inserts and secretes into the ...
, has a lower composition of oils. Although sweat is mostly water, there are many solutes which are found in sweat that have at least some relation to
biomarkers In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
found in blood. These include:
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
(Na+),
chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
(Cl),
potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
(K+),
ammonium The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary a ...
(NH),
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
s, lactate,
peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...
s &
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s. Development of devices, sensing techniques and biomarker identification in sweat continues to be an expanding field for medical diagnostics and athletics applications. The use of smart biosensors for on-skin sweat analysis has been described as internet-enabled Sudorology (iSudorology) by Brasier et al. in 2019. It describes the lab-independent detection of molecular, next-generation digital biomarkers in sweat.


History

Some of the earliest, published studies on sweat composition date back to the 19th century. Further studies in the 20th century began to solidify understanding of the physiology and pharmacology of the eccrine sweat gland.
In-vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and pl ...
and
in-vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
studies from this time period, and even those continuing today, have identified numerous structural nuances and new molecules present within sweat. The first commercially adopted use for sweat diagnostics included testing of sodium and chloride levels in children for the diagnosis of cystic fibrosis. Today, one of the most popular devices for this testing is the Macroduct Sweat Collection System from ELITechGroup.


General evidence

More recently, numerous studies have identified the plausibility of sweat as an alternative to blood analysis. The potential substitution for sweat versus blood analysis has many potential benefits. For example, sweat can be: extracted in a non-invasive manner via
iontophoresis Iontophoresis is a process of transdermal drug delivery by use of a voltage gradient on the skin. Molecules are transported across the stratum corneum by electrophoresis and electroosmosis and the electric field can also increase the permeability ...
; extracted with little-to-no pain; and monitored continuously. There are downfalls to the technology, however. For example, demonstration of successful and reliable sweat extraction and analysis on a cohesive device has yet to be demonstrated. Furthermore, although some biomarker partitioning mechanisms are well understood and well studied, partitioning of other useful biomarkers (
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s,
peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...
s, etc.) are less understood.


Current research


Portable devices


Patches

Patches have been demonstrated to be a promising detection platform for sweat diagnostics. Simple, long-term collection devices which check for drugs of abuse or alcohol are already on the market and operate on the following principle: a user applies the patch which then collects sweat over a period of hours or days, then the patch is analyzed utilizing techniques such as GC-MS which are accurate but have the drawback of lack of continuous measurements and high costs. For example, sweat diagnostic products for illicit drugs and alcohol are manufactured and supplied by PharmChek and AlcoPro, respectively. Recently several efforts have been made to develop low cost polymer based continuous perspiration monitoring devices and are in early stages of commercialization. More recently, startup companies such a
Xsensio
have begun developing products targeted towards the consumer, healthcare and athletics market for sweat diagnostics. Ultimately, it is the hope that these devices will have the ability to detect changes in human physiology within minutes without the need for repeated sample collection and analysis.


Temporary tattoos

Temporary tattoo-based sweat diagnostic tools have been demonstrated by Dr. Joseph Wang's group from
University of California, San Diego The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...
. Their work includes sweat diagnostics for sodium, lactate, ammonium, pH and
biofuel Biofuel is a fuel that is produced over a short time span from biomass, rather than by the very slow natural processes involved in the formation of fossil fuels, such as oil. According to the United States Energy Information Administration (E ...
opportunities.


References

{{reflist, refs= {{cite journal , vauthors = Mishra A, Greaves R, Massie J , title = The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era , journal = The Clinical Biochemist. Reviews , volume = 26 , issue = 4 , pages = 135–53 , date = November 2005 , pmid = 16648884 , pmc = 1320177 {{cite journal , vauthors = De Giovanni N, Fucci N , title = The current status of sweat testing for drugs of abuse: a review , journal = Current Medicinal Chemistry , volume = 20 , issue = 4 , pages = 545–61 , date = 2013 , pmid = 23244520 , doi = 10.2174/0929867311320040006 {{cite journal , vauthors = Wilke K, Martin A, Terstegen L, Biel SS , title = A short history of sweat gland biology , journal = International Journal of Cosmetic Science , volume = 29 , issue = 3 , pages = 169–79 , date = June 2007 , pmid = 18489347 , doi = 10.1111/j.1467-2494.2007.00387.x , doi-access = free {{cite journal , vauthors = Hoelscher JH , title = A Study in Perspiration.: Original Research in One Hundred and Thirteen Cases., journal = Journal of the American Medical Association , volume = 32 , pages = 1352–1360 , date = 1899 , doi = 10.1001/jama.1899.92450510001003 , url = https://zenodo.org/record/1447263 {{cite journal , vauthors = Nyman E, Palmlöv A , title = The elimination of ethyl alcohol in sweat. , journal = Skandinavisches Archiv für Physiologie , volume = 74 , issue = 2 , pages = 155–159 , date = 1936 , doi = 10.1111/j.1748-1716.1936.tb01150.x {{cite journal , vauthors = Schwartz IL, Thaysen JH , title = Excretion of sodium and potassium in human sweat , journal = The Journal of Clinical Investigation , volume = 35 , issue = 1 , pages = 114–20 , date = January 1956 , pmid = 13278407 , pmc = 438784 , doi = 10.1172/JCI103245 {{cite journal , vauthors = Sato K , title = The physiology, pharmacology, and biochemistry of the eccrine sweat gland , journal = Reviews of Physiology, Biochemistry and Pharmacology , volume = 79 , pages = 51–131 , date = 1977 , pmid = 21440 , doi = 10.1007/BFb0037089 , isbn = 978-3-540-08326-9 {{cite journal , vauthors = Sonner Z, Wilder E, Heikenfeld J, Kasting G, Beyette F, Swaile D, Sherman F, Joyce J, Hagen J, Kelley-Loughnane N, Naik R , title = The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications , journal = Biomicrofluidics , volume = 9 , issue = 3 , pages = 031301 , date = May 2015 , pmid = 26045728 , pmc = 4433483 , doi = 10.1063/1.4921039 {{cite journal , vauthors = Heikenfeld J , url = https://spectrum.ieee.org/biomedical/diagnostics/sweat-sensors-will-change-how-wearables-track-your-health , title = Sweat Sensors Will Change How Wearables Track Your Health , journal = IEEE Spectrum , date = 22 October 2014 {{cite journal , vauthors = Bandodkar AJ, Jia W, Wang J , title = Tattoo-Based Wearable Electrochemical Devices: A Review , journal = Electroanalysis , volume = 27 , issue = 3 , pages = 562–572 , date = 2015 , doi = 10.1002/elan.201400537 {{cite journal , vauthors = Sato K, Kang WH, Saga K, Sato KT , title = Biology of sweat glands and their disorders. I. Normal sweat gland function , journal = Journal of the American Academy of Dermatology , volume = 20 , issue = 4 , pages = 537–63 , date = April 1989 , pmid = 2654204 , doi = 10.1016/s0190-9622(89)70063-3 {{cite journal , vauthors = Pullan NJ, Thurston V, Barber S , title = Evaluation of an inductively coupled plasma mass spectrometry method for the analysis of sweat chloride and sodium for use in the diagnosis of cystic fibrosis , journal = Annals of Clinical Biochemistry , volume = 50 , issue = Pt 3 , pages = 267–70 , date = May 2013 , pmid = 23605131 , doi = 10.1177/0004563212474565 {{cite journal , vauthors = Czarnowski D, Górski J, Jóźwiuk J, Boroń-Kaczmarska A , title = Plasma ammonia is the principal source of ammonia in sweat , journal = European Journal of Applied Physiology and Occupational Physiology , volume = 65 , issue = 2 , pages = 135–7 , date = 1992 , pmid = 1396636 , doi = 10.1007/bf00705070 {{cite journal , vauthors = Cizza G, Marques AH, Eskandari F, Christie IC, Torvik S, Silverman MN, Phillips TM, Sternberg EM , title = Elevated neuroimmune biomarkers in sweat patches and plasma of premenopausal women with major depressive disorder in remission: the POWER study , journal = Biological Psychiatry , volume = 64 , issue = 10 , pages = 907–11 , date = November 2008 , pmid = 18657799 , pmc = 2610843 , doi = 10.1016/j.biopsych.2008.05.035 {{cite journal , vauthors = Banga AK, Chien YW , title = Iontophoretic delivery of drugs: fundamentals, developments and biomedical applications. , journal = Journal of Controlled Release , volume = 7 , pages = 1–24 , date = 1988 , doi = 10.1016/0168-3659(88)90075-2 {{cite web , author-link = Susan Scutti , vauthors = Scutti S , url = http://www.medicaldaily.com/measuring-your-sweat-health-monitor-and-diagnostic-device-future-wearable-technology-308408 , title = Measuring Your Sweat, A Health Monitor And Diagnostic Device Is The Future Of Wearable Technology , work = Medical Daily , date = 29 October 2014 {{cite web , first = Kathryn , last = Free , name-list-style = vanc , url = http://www.popularmechanics.com/science/health/a11097/temporary-tattoo-to-track-your-workout-2491688/ , title = A Temporary Tattoo to Track Your Workout and Charge Your Phone , work = Popular Mechanics , date = 13 August 2014 {{cite web , first = Rudy , last = Fenner , name-list-style = vanc , url = http://www.businesswire.com/news/home/20150508005547/en/CoreSyte-Selected-Worldwide-Athletics-Partner-Eccrine-Systems#.VW27LPlVhBc , title = CoreSyte Selected as Worldwide Athletics Partner by Eccrine Systems , work = Business Wire , date = 8 May 2015 {{cite web , first = Rose , last = Begonia , name-list-style = vanc , url = http://www.prnewswire.com/news-releases/kenzen-wearable-optimizes-athletic-performance-with-real-time-hydration-lactic-acid-and-glucose-analysis-300005504.html , title = Kenzen Wearable Optimizes Athletic Performance with Real-Time Hydration, Lactic Acid and Glucose Analysis , work = PR Newswire , date = 5 December 2014 Chemical pathology Skin tests