Overview:

Barrier function background

There is an increasing realization of the importance of the barrier in the development, characterization and management of a range of disorders. Barrier defects have been reported in atopic dermatitis (AD), asthma, chronic rhinosinusitis, allergic rhinitis, esophagitis and colitis. Assessment of barrier impairment provides insight into these disorders, but the assessment of skin barrier has to date been limited to research methods as they are not suited for clinical use . Atopic dermatitis (AD) is the most common, complex chronic inflammatory skin disease. It is well known that an impaired skin barrier is a critical factor in the development of atopic dermatitis or eczema. Skin barrier dysfunction is the initial step in the development of AD, and poor skin barrier function at birth is predictive of the development of atopic dermatitis.

It has also been shown that atopic dermatitis or impaired skin barrier often precedes food allergy because reduced skin barrier function allows environmental food allergens to penetrate the skin leading to systemic allergen sensitization. This is called “The atopic march” and refers to the natural progression of atopic diseases from atopic dermatitis in infancy to atopic asthma in school age children.

A new hypothesis called “The Epithelial Barrier Hypothesis” has been presented in an article in the journal Nature Reviews (Akdis, “Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?” Nature Reviews 2021). The research has its origin based on that there has been a steep increase in allergic and autoimmune diseases affecting more than one billion people worldwide. Intact skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as they protect host tissues from infections, environmental toxins, pollutants and allergens. A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis and many more diseases. The article introduces an extended ‘epithelial barrier hypothesis’, which proposes that the increase in epithelial barrier- damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. The hypothesis is also presented in a video, please follow this https://www.youtube.com/watch?v=cUeCM0wLGRw

Skin Barrier assessments with EIS

Previous work

The research has applied SciBase’s Electrical Impedance Spectroscopy (EIS) system Nevisense, to a new clinical area, barrier-related disorders. Building on work done within atopic dermatitis (AD) by Stig Ollmar and SciBase over a decade ago, research has been done to assess skin barrier function in mice. The aim of the research, was to establish a method to assess the skin epidermal barrier function in vivo , so that it could be used as a diagnostic tool for barrier-related inflammatory disorders of the skin, such as AD. (please see section 2 in Publications)

Recent studies

A study entitled ‘Direct assessment of skin epithelial barrier by electrical impedance spectroscopy’ (See: https://onlinelibrary.wiley.com/doi/10.1111/all.13824), was published in the journal Allergy, European Journal of Allergy and Clinical Immunology, and conclude that ‘Electrical Impedance spectroscopy is a rapid and reliable diagnostic tool to detect skin barrier defects’. The study illustrates clear potential for the use of Nevisense in routine clinical evaluation of the barrier, and the investigation of barrier-related disorders.

Another study presented in Allergy and titled “Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis” (See: https://onlinelibrary.wiley.com/doi/10.1111/all.14842) showed that Nevisense and Electrical impedance spectroscopy measurements can be useful tool to detect skin barrier dysfunction in vivo, valuable for the assessment of AD severity, progression, and therapy efficacy in a clinical setting.

Future vision

The future vision for Nevisense within the barrier indication is a device that could be used to investigate the barrier quickly and easily in a routine clinical setting for e.g.  analysing treatment responses and selection of skin barrier defective patients. Early detection of skin barrier defective babies before atopic dermatitis starts is an unmet need, since these babies can be included in skin barrier protection programs to prevent the development of atopic dermatitis. Atopic dermatitis affects more than 10% of the world’s population and 80% of the patients are babies The breadth of the potential applications is extraordinary – disorders such as eczema, food allergies and asthma, and even some gastrointestinal disorders involve the barrier.

Hear SciBase CEOs thoughts on the impact of EIS and AI on skin barrier diagnostics

For more information, please see: https://scibase.com/new-study-opens-up-new-applications-for-scibases-product-nevisense/

 

Products/Solutions

The Nevisense product family, consisting of the device Nevisense and the smaller pen-size device Nevisense Go, bothperform electrical impedance measurements that reflects objective information on cellular structure, cellular orientation, size and other properties of the skin which are not available to any visual method for assessing skin barrier characteristics.

 

Nevisense Go

Nevisense Go is, the latest and most advanced tool for measuring electrical impedance of the skin.

Nevisense Go is a handheld and fully portable device the size of a large Pen.  It combines the company’s core Electrical Impedance Spectroscopy (EIS) measurement technology with a new AI-based analysis platform embedded in the device. Each measurement gathers 220 datapoints, from 1 kHz to 1MHz at 10 permutations and 4 depth settings, providing comprehensive analysis of the area being measured.

The result is a flexible tool that will allow easy collection of data and development of new applications.

The first Nevisense Go version is released for skin barrier assessment, targeted at research and clinical study applications, and does not include a clinical indication (i.e. a non-medical device).

Nevisense Go provides a score after each measurement from an inbuilt AI classifier. It is however possible to download all measurement datapoints for further analysis and development, making Nevisense Go a powerful tool for skin barrier research.

Details:

Nevisense Go Handheld impedance meter with built in AI analysis
Size 190mm (h), 40mm (w), 25 mm (d), 1,3” (display)
Weight 120 grams
Product safety IEC 60601-1-2 Electromagnetic compatibility, IEC 62133-2
Connectivity Wi-Fi & Bluetooth capabilities
Battery Internal Lithium Polymer 3.7Wh.
Measurement frequencies 11 frequencies logarithmically distributed between 1kHz and 1MHz
Measurement levels Max measurement current = 10 µA
Max measurement voltage = 150 mV

 

Nevisense

Nevisense is a medical device with regulatory approval for detection of skin cancer, but can also be used for barrier research.

The Nevisense system consists of a control unit (1), a probe (2) and disposable electrodes (3). The control unit is used for user interaction through a touch screen and for signal processing of the impedance measurement signals, displaying the electrical impedance measurements on the screen.

Each measurement gathers 700 datapoints, from 1 kHz to 2,5 MHz at 10 permutations and 4 depth settings, providing comprehensive analysis of the area being measured.

It is possible to download all measurement datapoints for further analysis and development, making Nevisense a powerful tool for skin barrier research.

Nevisense  
Control unit screen The control unit has a 12” 800×600 color display with touch screen.
Measurement principle and frequencies Bioimpedance of the skin is measured micro invasively. Nevisense registers phase and magnitude in four different depths and ten permutations at 35 different frequencies from 1.0 kHz to 2.5 MHz.
Battery Battery status is indicated on the screen.
Control unit size 150 mm (h) x 400 mm (w) x 300 mm (d)
System weight Control unit 4 kg, probe unit 100g, battery 420g.
Product safety The CE-marked products fulfils the quality and safety regulations according to MDR for the clinical indication of skin cancer.
External interfaces The system is equipped with two USB ports.
Network Connectivity Nevisense supports connection to local area networks over Ethernet and WiFi.

 

 

Microinvasive electrode

SciBase´s proprietary disposable electrodes enable the electrical signals to reach the depths necessary to gather complete information about the properties of the skin.

The electrode has 5 gold plated bars with 45 microinvasive pins on each bar. The pins function is to penetrate into stratum corneum to warrant adequate electrical contact between the electrode and the underlying skin.

Each of the 5 bars of the electrode can send and receive electrical signals enabling complete coverage of the measurement area at 4 depths and 10 possible permutations over the frequency range of a measurement.

 

Nevisense Dashboard

The dashboard is a web-based visualization and analysis tool. Measurements can be exported from Nevisense or Nevisense Go and imported into the Dashboard.

In the dashboard, it is possible to

  • View and compare measurements,
  • Review all measurement data points (magnitude and phase shift over the measured frequencies)
  • Review calculated parameters, with features associated with bariier function, as well as any AI based analysis.
  • perform aggregate comparisons (scatter or boxplots) between selected parameters.
  • Export and import the data to/from Excel (where additional datatypes can be added and re-analyzed in the Dashboard

 

Q/A

What studies has been done so far?

  • Several studies have been performed, both as previous basic work, but also more recent, which shows the potential of EIS in skin barrier assessment. Please see menu “Skin Barrier assessment” under Barrier and “Publications” under EIS Technology.

How does EIS compare to TEWL?

  • EIS measures a different physiological parameter compared to Trans Epidermal Water Loss (TEWL) Whereas TEWL measures the amount of water evaporating from the skin, and provides one single value, EIS measures 2 parameters at 10 permutations over a frequency range, i.e., a large dataset in each measurement. Furthermore, it was shown in a clinical study (Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis) that EIS had better correlation to barrier related disease and biomarkers compared to TEWL.

What other areas except for AD could this be interesting to do research on?

  • All other barrier related conditions, such as psoriasis but also other allergic disorders related to a defective skin barrier.

How does the AI work? How can I use it?

  • Barrier related parameters are calculated after each measurement. However, to exploit the full potential of research or studies of the skin barrier, complete measurements over the frequency range are stored in the device and can be exported for further analysis, either in your own platforms or by importing the data into the Nevisense Dashboard, where all results can be presented and compared.
  • For further analysis or AI development, SciBase can provide support and access to an AI development platform from the company Peltarion , in order to develop AI based classifiers for new areas or indications.

Is this a medical device? Can anyone buy it?

  • Nevisense is today not classified as a medical device, but is to be used for research or studies. It conforms to IEC 60601-1-2 Electromagnetic compatibility, IEC 62133-2

How can a barrier score be developed and is it specific for one clinical indication?

  • A barrier score is developed through studies that investigate differences in skin properties in different population groups. You can investigate e.g., dry skin vs normal, psoriasis vs normals etc. The AI could then evaluate what kind of separation can be made between group. In cases where a separation between groups can be identified , an AI model with a relevant significance can be developed based on a sufficiently large sample size..