This article was submitted to Tissue Engineering and Regenerative Medicine, a section of the journal Frontiers in Bioengineering and Biotechnology
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Wound management in Space is an important factor to be considered in future Human Space Exploration. It demands the development of reliable wound monitoring systems that will facilitate the assessment and proper care of wounds in isolated environments, such as Space. One possible system could be developed using liquid crystal films, which have been a promising solution for real-time
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Although injuries, traumatic events, and surgical emergencies have been unlikely during the current space missions, their occurrence must be considered for future human space explorations. During long-lasting Space-missions, wound treatment and monitoring could become a fundamental problem, demanding more research in this area (
When a wound occurs, the first step is to assess its severity, which will form the basis for the following treatment. Clinical assessment of the wound is still the most common and cost-efficient method to assess wound severity. This method relies on a subjective evaluation of the wounds’ external features, such as size of the wound, wound edges, site of wound, wound bed (colour, amount of granulation tissue), presence of necrotic tissue, wound’s depth, level of exudate, and pain caused by the wound (
Among many clinical biomarkers, special attention has been given to pH (
A common way to measure wound temperature is by means of Infrared (IR) thermography (
The field of flexible and wearable bioelectronics, capable of monitoring physiological information and assisting in proper treatment is growing exponentially (
Ideally, a smart sensor for wound monitoring should have specific properties, such as 1) wearability/ability to adapt to the body shape, 2) biocompatibility, 3) high sensitivity, 4) easy-to-use, and 5) no external power. Due to these requirements, sensors based on the colourimetric approach appear as an ideal solution (
LCs are a unique state of matter between crystalline solid and isotropic liquid. In thermotropic LCs, phase transitions from crystalline solid to smectic, cholesteric and, finally, isotropic liquid, are caused by temperature changes, and they are mainly composed of rod-like molecules. In cholesteric LCs, also known as chiral LCs, molecules are inherently chiral, and the average molecular orientation is twisted with a certain periodicity, leading to a helical structure. This structure is characterised by a helical pitch that refers to the distance over which the LC molecules undergo a whole 360° twist. The size of this pitch determines the wavelength of the reflected light. The pitch of a cholesteric LC can be of the order of magnitude that corresponds to the wavelength spectra of visible light, allowing structural colouration to occur. An increase in the temperature results in a decrease in the pitch, which causes a shift in the wavelength of the reflected light. This presents the basis of the sensing principle of cholesteric LCs (
A study from 2017 (
This work compares the sensing ability of LCs with respect to IR thermography. To this aim, temperature mappings of surfaces of different topographies obtained using LCs sensing elements are compared against the ones obtained using IR thermography. The IR thermography is chosen as a reference since it is the most widespread technique used in wound temperature studies (
In this work, thermotropic LCs were prepared using Cholesteryl oleyl carbonate, Cholesteryl pelargonate and Cholesteryl benzoate (Sigma-Aldrich). Four thermotropic LCs were prepared, with different pitch values, by varying the concentration of the aforementioned components, as shown in
Liquid crystals samples series.
Sample name | Cholesteryl oleyl carbonate (wt%) | Cholesteryl pelargonate (wt%) | Cholesteryl benzoate (wt%) |
---|---|---|---|
LC1 | 35 | 55 | 10 |
LC2 | 32.5 | 57.5 | 10 |
LC3 | 30 | 60 | 10 |
LC4 | 25 | 65 | 10 |
The first step in the research presented here was the choice of LCs formulation that has an optical activation range in a temperature range that is useful for wound monitoring. For this purpose, transmission spectra of 4 LCs formulations (see
The liquid crystal sensing element (also referred as sensing patch) consists of three layers: a bottom polydimethylsiloxane elastomer/carbon black (PDMS/CB) layer, a middle LC sensing layer and a top transparent PDMS elastomer (PDMS) layer. The sensing patch was produced following the steps shown in
Liquid crystal sensing patch with arrays: production steps.
The first step in the fabrication process was a production of a thin black bottom elastomer layer. PDMS SYLGARD™ 184 (Dow Inc.) and CB, particle size 4
The second step was PDMS/CB surface activation with oxygen plasma, to increase the hydrophilicity of PDMS/CB film. Before plasma treatment, PDMS films were cleaned from dust using scotch tape. Films were treated with oxygen plasma using a plasma cleaner (PDC-002 (230 V) Haarrick Plasma) for 15 min, using the maximum power–30 W. The water contact angles before and after the treatment are shown in
The third step was an LCs dots array fabrication on the PDMS/CB layer, achieved using the blade coating technique. The plane surface was converted to a grid of dots to obtain the uniform colour response, and this was achieved by blade coating over the patterned paper mask. The mask was designed in CorelDraw, with the final dimensions of 50 mm × 50 mm, containing 324 dots with a diameter of 1.5 mm, and a 1 mm distance between them. A laser cutter (EpilogLaser mini) was then used to cut the paper sheet (thickness 100
The final step was to cover LC pattern film with the protective transparent PDMS layer, using the spin coating technique (speed 500 rpm, time 30 s). Digital photos of the patch adapting to the different body surface is shown in
In general, an experimental setup for the calibration of thermotropic LCs should consist of a calibration surface with a temperature sensor, imaging system, heating and cooling system, and illumination source. The experimental setup, shown in
In order to use thermotropic LCs for quantitative temperature measurements, the determination of the relation between temperature and colour is a necessary step. Several ways to specify colour include the Red, Green and Blue (RGB), and the Hue-Saturation-Value (HSV) model. Researchers have widely used Hue to quantify colour due to its simplicity and independence with respect to illumination intensity. It is considered that the analysis of HSV data represents the simplest and most straightforward analysis approach. Hue (in degrees °) is what people typically refer to when using the term “colour.” Saturation describes the degree to which a pure colour is diluted with white. It identifies how pure or intense the colour is. The value (brightness) of colour identifies how light or dark the colour is. In the following graphs, Hue will be used to quantify the colour.
This calibration of the patch should be done in an environment as close as possible to the conditions in which it will be used. The calibration was then performed in a laboratory open space so as to simulate normal utilization conditions, e.g., patients at home. Before each test, temperature and humidity in the laboratory were measured.
Before placing the sample on the aluminium plate, an automatic white balance was carried out on the white background to calibrate the colour temperature. Once the sample was placed, TS2 was in direct contact with the bottom of the patch. During the test, the temperature was increased or decreased in the cooling case, with steps of 0.1°C. When the temperature measured with TS2 was stable, photos were taken. Exposure time was set to 10,200 ms and ten pictures for each temperature were taken. RGB values were collected from dots that were in direct contact with the TS2.
In general, the sensor’s repeatability is considered to be an important parameter, mainly if the sensor should be used multiple times and be exposed to heating and cooling conditions, like in the case of a sensor that would be used in wound monitoring. To test this property systematically, six different full-range calibrations were performed within 3 days. Each day, the first test was dedicated to heating, and the second test for cooling. Between these calibrations, the patch was stored in ambient conditions. The sample was not moved from its original place during this 3-day period, and hue values were calculated on the same spot.
Response time is another important sensors’ characteristic. In this study, response time was measured using a dynamic test. First, the sample patch was placed on the aluminium plate and then the temperature was set to 34°C. The monitoring started after the system was stabilised, i.e., TS2 temperature and Hue were not changing. During the test, temperature from sensor TS2 was constantly monitored (20 values per second), and images were taken automatically (10 frames per second) using a colour camera. When the monitoring started, the set-point temperature was changed from 34 to 37°C.
A C++ application was developed to allow quantitative reading of the temperature using the LCs patch. An example of the temperature reading is shown in
The interface of the application used for quantitative analysis of temperature from the LC patch.
The goal was to directly compare the temperature distribution of the same surface obtained using the LCs patch with the one recorded using an Infrared Thermal Imaging Camera, FLIR T425 with a 320 × 240-pixel resolution. This test was performed on the same setup used for calibration. In this case, instead of an aluminium plate, we used flat surfaces composed of two materials with different thermal conductivities, aluminium (thermal conductivity 237 W/mK) and an acrylic sheet (0.2 W/mK). Three different surfaces were prepared, where the base was an aluminium plate with different 3D shapes engraved using a CNC machine and opposite acrylic masks. The goal of creating these plates is to get a flat surface that will, during heating, have different temperature distributions on the top. This will mimic the temperature distribution at the wound and surroundings. Digital photos of the surfaces are shown in
Transmittance spectra of LCs are shown in
The colorimetric response of different LC upon changing temperature (29.9–44.6°C):
Thermotropic LC spectrophotometry: calibration curves. All calibration curves showed a second-order polynomial trend.
Liquid crystals response range and sensitivity. Measurement done using the spectrophotometer.
Sample Name | Linear response range 1 (°C) | Linear range sensitivity 1 (nm/°C) |
|
Linear response range 2 (°C) | Linear range sensitivity 2 (nm/°C) |
|
---|---|---|---|---|---|---|
LC1 | 29.9–32.0 | 89.7 | 0.95 | 32.1–35.1 | 25.3 | 0.98 |
LC2 | 32.6–35.9 | 71.2 | 0.98 | 36.0–38.7 | 18.9 | 0.98 |
LC3 | 36.9–39.5 | 78.6 | 0.97 | 36.6–41.9 | 23.7 | 0.98 |
LC4 | 40.9–43.1 | 81.6 | 0.88 | 43.2–44.7 | 31.2 | 0.94 |
Photos used for calibration are shown in
LC2 patch colorimetric response during heating and calibration.
Hue-saturation values are presented in
LC2 patch: repeatability.
LC2 patch: Temperature shift (°C) compared to the first heating calibration curve.
Hue (°) | Cooling 1 | Heating 2 | Cooling 2 | Heating 3 | Cooling 3 |
---|---|---|---|---|---|
50 | 0.25 | 0.09 | 0.20 | 0.33 | 0.47 |
100 | 0.24 | 0.09 | 0.19 | 0.29 | 0.42 |
150 | 0.23 | 0.1 | 0.18 | 0.26 | 0.37 |
200 | 0.22 | 0.1 | 0.17 | 0.22 | 0.32 |
LC2 patch sensitivity in effective temperature region 34–37.1°C.
Measurement | Sensitivity (°/°C) |
|
---|---|---|
Heating day 1 | 72.8 | 0.99 |
Cooling day 1 | 71.8 | 0.97 |
Heating day 2 | 73.1 | 0.98 |
Cooling day 2 | 71.6 | 0.98 |
Heating day 3 | 69.4 | 0.97 |
Cooling day 3 | 67.74 | 0.97 |
During the repeatability test, it was observed that the hue temperature relationship depends upon whether the crystals are undergoing a cooling or heating cycle. This difference is known as the hysteresis effect. The hysteresis effect was studied by heating the patch until 40°C and cooling it down until 32.5°C. Hue was calculated during heating and cooling for steps of 0.1°C. Corresponding RGB-temperature and Hue-temperature curves are presented in
LC2 patch: Hysteresis effect. The patch was first heated until reaching the isotropic phase, and cooled down.
Changes in temperature and hue are presented in
Response time of LC2 patch. The set point temperature was changed from 34 to 37°C (black line), and the temperature sensor TS2 measured the temperature at the bottom of the patch (T2-blue curve). At the same time changes in Hue were calculated (red curve). Intimidate reaction in hue changes how the temperature is changing was reported.
Results are shown in
Comparison between LCs patch and IR imaging. Three surfaces
Comparison between temperature measurements using LCs patches and application against the ones measured using IR imaging.
Measured area | Tmax [°C] | Tmin [°C] | Taverage [°C] | ΔT [°C] | ||
---|---|---|---|---|---|---|
Shape1 | IR | S1 | 34.8 | 32.8 | 33.9 | 2.6 |
S2 | 37 | 35.8 | 36.5 | |||
LC | S1 | 36.8 | 33.2 | 35.4 | 1.9 | |
S2 | 38.4 | 36.5 | 37.3 | |||
Shape2 | IR | S1 | 34.6 | 32.1 | 32.8 | 3.1 |
S2 | 37.5 | 31.6 | 35.9 | |||
LC | S1 | 36.5 | 33.1 | 34.9 | 2.5 | |
S2 | 38.8 | 36.3 | 37.5 | |||
Shape3 | IR | S1 | 35.8 | 33.6 | 34.4 | 1.8 |
S2 | 36.4 | 35.9 | 36.2 | |||
LC | S1 | 36.5 | 34.0 | 36.1 | 1.8 | |
S2 | 38.3 | 36.6 | 37.9 |
As described in the introduction, IR thermography is commonly used to measure temperature distributions in wound studies. IR thermal cameras are sensitive to environmental conditions. Before imaging, IR cameras require input values including room temperature, humidity, distance from the object and its emissivity. It is not always possible to correctly determine these parameters, although they are directly influencing the reading output. The emissivity of human skin is considered to be between 0.97–0.99 (
In general, this study showed that LCs have the potential to fabricate advanced temperature distribution sensors. This is not common to other sensing elements, such as resistance or impedance-based ones, that could measure only point-wise values. Another important advantage of this configuration is its simplicity in reading the output. When compared with infrared imaging, LCs are capable of reproducing the main features of the temperature fields surrounding a wound mimicking shape, even geometrically complex. However, the recognition of the patterns was somewhat less sharp for the LCs with respect to the IR camera. This might be caused by the contact between the patch and the to-be-measured surface.
The thermotropic LCs used in this research can detect even small temperature variations (high sensitivity) and have a good repeatability as well as a fast response time (less than 0.5 s). However, LCs used here have a narrow bandwidth, resulting in high sensitivity but a small effective temperature range. The temperature range can be extended by changing the type of thermotropic LCs or by changing the component ratio. According to (
The ageing of LCs reduces their shelf life. Proper preparation and storage are necessary to minimize their ageing. It was suggested that pure thermotropic LCs should not be exposed to fats, greases, organic solvents and dust. They can also be susceptible to UV and IR radiation, and exposure to these sources reduces the shelf life (
Note that the technological readiness of LCs, although promising, does not directly translate into the possibility to include them in clinical trials. Several issues should be considered in that respect and they will be discussed below.
Wound contamination: the current status of the proposed patch requires that it should be in direct contact with the wound. In clinical practice, medical personnel are obliged to use wound dressings to avoid contamination, protect wounds, and promote wound healing. Nowadays, an ideal wound should fulfil the following characteristics: 1) creating a moist and warm environment around the wound, 2) allowing gas exchange, 3) protecting the wound from bacterial infections, 4) creating a mechanical protection, 5) controlling the exudate level, 6) being biocompatible, non-toxic, non-allergenic, 7) being easily removable, i.e., the material should be non-adhering to avoid removing of a newly formed tissue, 8) being able to stimulate healing, and 9) being costly acceptable (
Size of the wounds: in literature it is possible to find an outstanding number of wound sensors, either based on LCs or not. Everyone who participated to a real clinical study on wound imaging knows that serious wounds, and especially burns, could cover large portions of the body, sometimes even the whole body. It is evident that the development of a contact sensor that would monitor such a wound is currently not possible.
Shape and 3D nature of the wounded tissues distributions: although maybe technically possible, it is very difficult to imagine a contact sensor when the shape and distribution of the wounds is not flat or even worse, changing “volumetrically” during the healing time. It would be possible to think of an intermediate layer hosting the sensing element. If this solution could potentially solve the flatness problem, it will also challenge the capability of this layer to transmit reliably biophysical signals from the wound to the sensing element.
Although it is beyond the scope of this paper to provide a complete overview of the clinical requirements for wound diagnosis and follow-up, it is possible to draw preliminary conclusions. LCs could represent a complementary element to support the medical decision and follow-up in the case of wounds, especially burns. However, the application of such kinds of sensors in clinical practice is far from being straightforward, and the plethora of sensors’ concepts presented in the literature are still at a low-TRL stage.
The original contributions presented in the study are included in the article/
VM and CI contributed to the design and conception of the study. VM, with the help of CM and EM, carried out measurements. VM and CI drafted the article. VM created tables and figures. VM, CI, CV, and HM participated in the revision process of the article and gave final approval of the submitted version.
This work was funded through the WHISKIES, a ESA-sponsored Microgravity Application Promotion. We also thank the Alice and David Van Buuren Fund and Foundation Jaumotte-Demoulin for the provided funds.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
The Supplementary Material for this article can be found online at:
liquid crystal
Infrared
carbon black
temperature sensor