Sweat diagnostics

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Sweat diagnostics
Purposetest for Eccrine sweat gland(mostly)

Sweat diagnostics is an emerging non-invasive technique used to provide insights to the health of the human body. Common sweat diagnostic tests include testing for cystic fibrosis [1] and illicit drugs. [2] Most testing of human sweat is in reference to the eccrine sweat gland which in contrast to the apocrine sweat gland, has a lower composition of oils. [3]

Contents

Although sweat is mostly water, [3] there are many solutes which are found in sweat that have at least some relation to biomarkers found in blood. These include: sodium (Na+), chloride (Cl−), potassium (K+), ammonium (NH+
4), alcohols, lactate, peptides & proteins. [4] [5] 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. [6]

History

Some of the earliest, published studies [7] on sweat composition date back to the 19th century. Further studies [8] [9] [10] in the 20th century began to solidify understanding of the physiology and pharmacology of the eccrine sweat gland. In-vivo and in-vitro 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. [11]

General evidence

More recently, numerous studies have identified the plausibility of sweat as an alternative to blood analysis. [12] [13] 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; extracted with little-to-no pain; and monitored continuously. [14] 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 (cytokines, peptides, etc.) are less understood. [4]

Current research

Portable devices

Patches

Patches have been demonstrated to be a promising detection platform for sweat diagnostics. [15] [16] [17] 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 [18] have been made to develop low cost polymer based continuous perspiration monitoring devices and are in early stages of commercialization. [19]

More recently, startup companies such as 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. [20]

Temporary tattoos

Temporary tattoo-based sweat diagnostic tools [21] have been demonstrated by Dr. Joseph Wang's group from University of California, San Diego. Their work includes sweat diagnostics for sodium, lactate, ammonium, pH and biofuel opportunities. [22]

Related Research Articles

<span class="mw-page-title-main">Cystic fibrosis</span> Autosomal recessive disease mostly affecting the lungs

Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. The hallmark feature of CF is the accumulation of thick mucus in different organs. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.

<span class="mw-page-title-main">Perspiration</span> Fluid secreted from sudoriferous glands

Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals.

<span class="mw-page-title-main">Fatty liver disease</span> Medical condition related to obesity

Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.

<span class="mw-page-title-main">Cystic fibrosis transmembrane conductance regulator</span> Mammalian protein found in humans

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the CFTR gene.

<span class="mw-page-title-main">Sweat gland</span> Small sweat-producing tubular skin structures

Sweat glands, also known as sudoriferous or sudoriparous glands, from Latin sudor 'sweat', are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial surface by way of a duct. There are two main types of sweat glands that differ in their structure, function, secretory product, mechanism of excretion, anatomic distribution, and distribution across species:

The sweat test measures the concentration of chloride that is excreted in sweat. It is used to screen for cystic fibrosis (CF). Due to defective chloride channels (CFTR), the concentration of chloride in sweat is elevated in individuals with CF.

<span class="mw-page-title-main">Spiperone</span> Chemical compound

Spiperone (Spiroperidol; brand name: Spiropitan(JP)) is a typical antipsychotic and research chemical belonging to the butyrophenone chemical class. It is licensed for clinical use in Japan as a treatment for schizophrenia. Additionally, spiperone was identified by compound screening to be an activator of Ca2+ activated Cl− channels (CaCCs), thus a potential target for therapy of cystic fibrosis.

<span class="mw-page-title-main">Epithelial sodium channel</span> Group of membrane proteins

The epithelial sodium channel(ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na+). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.

<span class="mw-page-title-main">Eccrine sweat gland</span> Sweat gland distributed almost all over the human body

Eccrine sweat glands are the major sweat glands of the human body. Eccrine sweat glands are found in virtually all skin, with the highest density in the palms of the hands, and soles of the feet, and on the head, but much less on the torso and the extremities. In other mammals, they are relatively sparse, being found mainly on hairless areas such as foot pads. They reach their peak of development in humans, where they may number 200–400/cm2 of skin surface. They produce sweat, a merocrine secretion which is clear, odorless substance, consisting primarily of water. These are present from birth. Their secretory part is present deep inside the dermis.

Sudomotor function refers to the autonomic nervous system control of sweat gland activity in response to various environmental and individual factors. Sweat production is a vital thermoregulatory mechanism used by the body to prevent heat-related illness as the evaporation of sweat is the body’s most effective method of heat reduction and the only cooling method available when the air temperature rises above skin temperature. In addition, sweat plays key roles in grip, microbial defense, and wound healing.

<span class="mw-page-title-main">Carbonic anhydrase 12</span> Protein-coding gene in the species Homo sapiens

Carbonic anhydrase 12 is an enzyme that in humans is encoded by the CA12 gene.

<span class="mw-page-title-main">Channel blocker</span> Molecule able to block protein channels, frequently used as pharmaceutical

A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel.

<span class="mw-page-title-main">Poroma</span>

Poromas are rare, benign, cutaneous adnexal tumors. Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated towards one or more of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. Poromas are eccrine or apocrine sweat gland tumors derived from the cells in the terminal portion of these glands' ducts. This part of the sweat gland duct is termed the acrosyringium and had led to grouping poromas in the acrospiroma class of skin tumors. Here, poromas are regarded as distinct sweat gland tumors that differ from other sweat gland tumors by their characteristic clinical presentations, microscopic histopathology, and the genetic mutations that their neoplastic cells have recently been found to carry.

Porocarcinoma (PCA) is a rare form of skin cancer that develops in eccrine sweat glands, i.e. the body's widely distributed major type of sweat glands, as opposed to the apocrine sweat glands which are located primarily in the armpits and perineal area. This cancer typically develops in individuals as a single cutaneous tumor in the intraepidermal spiral part of these sweat glands' ducts at or near to where they open on the skin's surface. PCA tumors are classified as one form of the cutaneous adnexal tumors; in a study of 2,205 cases, PCA was the most common (11.8%) form of these tumors.

<span class="mw-page-title-main">Eccrine carcinoma</span> Medical condition

Eccrine carcinoma is a rare skin condition characterized by a plaque or nodule on the scalp, trunk, or extremities. It originates from the eccrine sweat glands of the skin, accounting for less than 0.01% of diagnosed cutaneous malignancies. Eccrine carcinoma tumors are locally aggressive, with a high rate of recurrence. Lack of reliable immunohistochemical markers and similarity to other common tumors has made identification of eccrine carcinoma difficult.

Transepithelial potential difference (TEPD) is the voltage across an epithelium, and is the sum of the membrane potentials for the outer and inner cell membranes.

<span class="mw-page-title-main">Acrospiroma</span> Medical condition

Acrospiromas are a broad class of benign cutaneous adnexal tumors. Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated towards one or more of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. Acrospiromas are thought to derive from apocrine or eccrine sweat gland ducts near their acrosyringium, i.e. point where these ducts open to the skin's surface.

Elexacaftor/tezacaftor/ivacaftor, sold under the brand names Trikafta (US) and Kaftrio (EU), is a fixed-dose combination medication used to treat cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor is composed of a combination of ivacaftor, a chloride channel opener, and elexacaftor and tezacaftor, CFTR modulators.

Electrochemical skin conductance (ESC) is an objective, non-invasive and quantitative electrophysiological measure of skin conductance through the application of a pulsating direct current on the skin. It is based on reverse iontophoresis and steady chronoamperometry. ESC is intended to provide insight into and assess sudomotor function and small fiber peripheral neuropathy. The measure was principally developed by Impeto Medical to diagnose cystic fibrosis from historical research at the Mayo Clinic and then tested on others diseases with peripheral neuropathic alterations in general. It was later integrated into health connected scales by Withings.

<span class="mw-page-title-main">Cystic fibrosis and race</span>

Underrepresented populations, especially black and hispanic populations with cystic fibrosis are often not successfully diagnosed. This is in part due to the minimal dissemination of existing data on patients from these underrepresented groups. While white populations do appear to experience a higher frequency of cystic fibrosis, other ethnicities are also affected and not always by the same biological mechanisms. Thus, many healthcare and treatment options are less reliable or unavailable to underrepresented populations. This issue affects the level at which public health needs are being met across the world.

References

  1. ↑ Mishra A, Greaves R, Massie J (November 2005). "The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era". The Clinical Biochemist. Reviews. 26 (4): 135–53. PMC   1320177 . PMID   16648884.
  2. ↑ De Giovanni N, Fucci N (2013). "The current status of sweat testing for drugs of abuse: a review". Current Medicinal Chemistry. 20 (4): 545–61. doi:10.2174/0929867311320040006. PMID   23244520.
  3. 1 2 Wilke K, Martin A, Terstegen L, Biel SS (June 2007). "A short history of sweat gland biology". International Journal of Cosmetic Science. 29 (3): 169–79. doi: 10.1111/j.1467-2494.2007.00387.x . PMID   18489347.
  4. 1 2 Sonner Z, Wilder E, Heikenfeld J, Kasting G, Beyette F, Swaile D, Sherman F, Joyce J, Hagen J, Kelley-Loughnane N, Naik R (May 2015). "The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications". Biomicrofluidics. 9 (3): 031301. doi:10.1063/1.4921039. PMC   4433483 . PMID   26045728.
  5. ↑ Sato K, Kang WH, Saga K, Sato KT (April 1989). "Biology of sweat glands and their disorders. I. Normal sweat gland function". Journal of the American Academy of Dermatology. 20 (4): 537–63. doi:10.1016/s0190-9622(89)70063-3. PMID   2654204.
  6. ↑ Brasier N, Eckstein J (2019). "Sweat as a Source of Next-Generation Digital Biomarkers". Digital Biomarkers. 3 (3): 155–165. doi:10.1159/000504387. PMC   7011725 . PMID   32095774.
  7. ↑ Hoelscher JH (1899). "A Study in Perspiration.: Original Research in One Hundred and Thirteen Cases". Journal of the American Medical Association. 32: 1352–1360. doi:10.1001/jama.1899.92450510001003.
  8. ↑ Nyman E, Palmlöv A (1936). "The elimination of ethyl alcohol in sweat". Skandinavisches Archiv für Physiologie. 74 (2): 155–159. doi:10.1111/j.1748-1716.1936.tb01150.x.
  9. ↑ Schwartz IL, Thaysen JH (January 1956). "Excretion of sodium and potassium in human sweat". The Journal of Clinical Investigation. 35 (1): 114–20. doi:10.1172/JCI103245. PMC   438784 . PMID   13278407.
  10. ↑ Sato K (1977). "The physiology, pharmacology, and biochemistry of the eccrine sweat gland". Reviews of Physiology, Biochemistry and Pharmacology. 79: 51–131. doi:10.1007/BFb0037089. ISBN   978-3-540-08326-9. PMID   21440.
  11. ↑ Pullan NJ, Thurston V, Barber S (May 2013). "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". Annals of Clinical Biochemistry. 50 (Pt 3): 267–70. doi:10.1177/0004563212474565. PMID   23605131. S2CID   40347024.
  12. ↑ Czarnowski D, Górski J, Jóźwiuk J, Boroń-Kaczmarska A (1992). "Plasma ammonia is the principal source of ammonia in sweat". European Journal of Applied Physiology and Occupational Physiology. 65 (2): 135–7. doi:10.1007/bf00705070. PMID   1396636. S2CID   7994016.
  13. ↑ Cizza G, Marques AH, Eskandari F, Christie IC, Torvik S, Silverman MN, Phillips TM, Sternberg EM (November 2008). "Elevated neuroimmune biomarkers in sweat patches and plasma of premenopausal women with major depressive disorder in remission: the POWER study". Biological Psychiatry. 64 (10): 907–11. doi:10.1016/j.biopsych.2008.05.035. PMC   2610843 . PMID   18657799.
  14. ↑ Banga AK, Chien YW (1988). "Iontophoretic delivery of drugs: fundamentals, developments and biomedical applications". Journal of Controlled Release. 7: 1–24. doi:10.1016/0168-3659(88)90075-2.
  15. ↑ Scutti S (29 October 2014). "Measuring Your Sweat, A Health Monitor And Diagnostic Device Is The Future Of Wearable Technology". Medical Daily.
  16. ↑ Fenner R (8 May 2015). "CoreSyte Selected as Worldwide Athletics Partner by Eccrine Systems". Business Wire.{{cite web}}: CS1 maint: overridden setting (link)
  17. ↑ Begonia R (5 December 2014). "Kenzen Wearable Optimizes Athletic Performance with Real-Time Hydration, Lactic Acid and Glucose Analysis". PR Newswire.{{cite web}}: CS1 maint: overridden setting (link)
  18. ↑ Jain V, Ochoa M, Jiang H, Rahimi R, Ziaie B (2019-06-17). "A mass-customizable dermal patch with discrete colorimetric indicators for personalized sweat rate quantification". Microsystems & Nanoengineering. 5 (1): 29. Bibcode:2019MicNa...5...29J. doi:10.1038/s41378-019-0067-0. PMC   6572848 . PMID   31240108.
  19. ↑ US 10772560,Ziaie, Babak; Ochoa, Manuel P.& Jain, Vaibhavet al.,"Skin-mounted hydration sensor and management system",published 2020-09-15,issued 2017-10-02, assigned to Purdue Research Foundation
  20. ↑ Heikenfeld J (22 October 2014). "Sweat Sensors Will Change How Wearables Track Your Health". IEEE Spectrum.
  21. ↑ Free K (13 August 2014). "A Temporary Tattoo to Track Your Workout and Charge Your Phone". Popular Mechanics.{{cite web}}: CS1 maint: overridden setting (link)
  22. ↑ Bandodkar AJ, Jia W, Wang J (2015). "Tattoo-Based Wearable Electrochemical Devices: A Review". Electroanalysis. 27 (3): 562–572. doi:10.1002/elan.201400537.
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