- Email: [email protected]
Generation of electrical power under human skin by subdermal solar cell arrays for implantable bioelectronic devices
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
Contents lists available at ScienceDirect
Biosensors and Bioelectronics journal homepage: www.elsevier.com/locate/bios
Generation of electrical power under human skin by subdermal solar cell arrays for implantable bioelectronic devices Kwangsun Songa,b, Jung Hyun Hanc,d, Hyung Chae Yange, Kwang Il Namf, Jongho Leea,b,
⁎
a School of Mechanical Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea b Research Institute for Solar and Sustainable Energies, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea c School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea d Haenam Beautis Skin and Laser Clinic, 456-1 Haeri Haenam-gun, Jeollanamdo, 536-809, Republic of Korea e Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Republic of Korea f Department of Anatomy, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Republic of Korea
A R T I C L E I N F O
A BS T RAC T
Keywords: Solar cell Implantable Medical electronic implants Energy Human skin Bioelectronic devices
Medical electronic implants can significantly improve people's health and quality of life. These implants are typically powered by batteries, which usually have a finite lifetime and therefore must be replaced periodically using surgical procedures. Recently, subdermal solar cells that can generate electricity by absorbing light transmitted through skin have been proposed as a sustainable electricity source to power medical electronic implants in bodies. However, the results to date have been obtained with animal models. To apply the technology to human beings, electrical performance should be characterized using human skin covering the subdermal solar cells. In this paper, we present electrical performance results (up to 9.05 mW/cm2) of the implantable solar cell array under 59 human skin samples isolated from 10 cadavers. The results indicate that the power densities depend on the thickness and tone of the human skin, e.g., higher power was generated under thinner and brighter skin. The generated power density is high enough to operate currently available medical electronic implants such as pacemakers that require tens of microwatt.
1. Introduction As the average human lifespan continues to gradually increase, diverse medical electronic implants are becoming more important, to functionally assist internal organs, and to help maintain quality of life by treating chronic diseases. Cardiovascular, neurological and gastroenteric disorders are now being treated by implants, using devices such as cardiac pacemakers (Kurtz et al., 2010), deep brain stimulators (Mayberg et al., 2005), gastric stimulators (Cigaina, 2004) and diaphragmatic stimulators (Sardarzadeh, 2012). However, since the electrical capacity of the batteries which provide power to these medical electronic implants is finite, the batteries are usually large, occupying about half of the volume of the implants (Romero et al., 2009). In addition, the entire implant, including the battery, needs to be periodically replaced every 2–8 years through surgical intervention (Reese et al., 2011; Wood and Ellenbogen, 2002), which creates psychological, physical and financial burdens to patients (Kurtz et al.,
⁎
2010). At the same time, the finite electrical capacity that can be implanted in human bodies limits not only the practical use of mechanically sophisticated flexible and stretchable electronics (Kim et al., 2010; Ko et al., 2012; Labroo and Cui, 2013; Manunza and Bonfiglio, 2007; Reeder et al., 2014) for biomedical applications but is also insufficient for more advanced functionalities, such as real-time communication. Such devices require sustainable high electric power, for example, in advanced therapeutic and diagnostic medical implants including real-time glucose or blood pressure monitors (Fassbender et al., 2008; Yu et al., 2006), bio-signal sensors (Xu et al., 2015), drug delivery systems (Minev et al., 2015), artificial hearts (Copeland et al., 2004) and many others (Chow et al., 2004; Kuzum et al., 2014; Tahir et al., 2005; Wang, 2006). Recently, various energy harvesting strategies have been designed to make use of energy sources in the human body, including electrochemical reactions (Agnes et al., 2014; Katz and MacVittie, 2013; Liu et al., 2010), mechanical motion (Bai et al., 2013; Zhao et al., 2014), wireless energy transmission (Kim et al., 2012) and
Corresponding author. E-mail address: [email protected] (J. Lee).
http://dx.doi.org/10.1016/j.bios.2016.10.095 Received 4 August 2016; Received in revised form 10 October 2016; Accepted 31 October 2016 Available online xxxx 0956-5663/ © 2016 Elsevier B.V. All rights reserved.
Please cite this article as: Song, K., Biosensors and Bioelectronics (2016), http://dx.doi.org/10.1016/j.bios.2016.10.095
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
was measured under constant pressure on a motorized translational microstage equipped with a force sensor (transducer techniques) and top vacuum holder. To accomplish this, first, we adjusted the parallel alignment of the microstage and the top vacuum holder by using a twoaxis tilting stage. The force sensor and a square plate (size: 6 mm×6 mm) were installed on the motorized microstage and the top vacuum holder, respectively. After mounting a skin sample on the flat sensing plate of the force sensor, we slowly moved the microstage (resolution of z-axis: ~0.037 µm) vertically while monitoring the pressure in real time. We measured the thickness of the human skin sample when the applied pressure to the skin was 81.6 mN/cm2.
others (Carmo et al., 2010; Torres and Rincón-Mora, 2009). Some of these methods require further development to improve durability, biocompatibility or electric power output. Another alternative approach involves producing electricity from light transmitted through the skin by photoelectric effect (Amar et al., 2015; Goto et al., 2001; Hannan et al., 2014; Murakawa et al., 1999). Rigid solar cells, implanted into pig models, were found capable of supplying enough power to operate custom-built implants (Haeberlin et al., 2015, 2014). Subdermal flexible solar microcell arrays designed to be mechanically more compatible with skin also generated electricity to power electronic implants in mouse models (Song et al., 2016). Although these studies demonstrated the feasibility of the concept in animal models, the actual electrical characteristics under human skin must be considered in order to further develop the technology for human beings, since the performance of the device can depend on various features of the skin covering the solar cells. Here, we present the electrical performance of flexible implantable photovoltaic (IPV) devices under isolated human skin samples, whose results improve the chances for more realistic use of the implantable power source for human beings. Experiments conducted with skin samples from 6 locations of 10 human cadavers provide quantitative data for the factors (such as skin thickness and tone) that affect the amount of power generation under skin. Results indicate that the IPV devices under the human skin generate around 0.51–9.05 mW/cm2 depending on the thickness and tone of the skin. These results should be very important consideration in designing the sustainable power source for functional medical electronic implants.
2.4. Measuring optical properties of human skin We measured the optical properties of the isolated human skin samples with a fiber-optic spectrometer (Avantes) integrated with double integrating spheres. The double integrating spheres collect scattering light transmitted through translucent skin. We measured the amount of light transmitted (Ms) through human skin placed between the double integrating spheres, for wavelengths of 400– 900 nm. After removing the skin from between the spheres, we repeated the measurements with the light source on (Mw) and off (Md). The transmittance of the human (Ts) skin was calculated using the following equation: Ts=(Ms−Md)/(Mw−Md). We averaged 20 sets of measurements for each skin sample. 3. Results and discussion
2. Material and methods
3.1. Concept of the subcutaneously implantable solar cell for power generation in human body
2.1. Fabrication of flexible IPV device Fig. 1 illustrates the concepts involved in the subcutaneous implantation of solar microcells for electric power generation in human bodies. Since human skin (Fig. 1a) protects our bodies from bacteria, viruses and many other unwanted substances, delivering electrical power to medical electronic implants through electrical wires penetrating the skin may put the body at risk of infection. Generating the necessary electrical power under the skin can avoid that risk. Fig. 1b shows a histological microscope image of shoulder skin, separated from a human cadaver (race: Asian, ages: 82, male) that was preserved by an embalming solution composed of ethanol, glycerin, formalin, phenol and distilled water, and stained with Accustain trichrome stain (Masson) kit (Sigma-Aldrich). The shoulder skin consists of three primary layers: the epidermis (~32 µm), dermis (~1.8 mm) and subcutaneous fat. Although human skin is not optically transparent, a fraction of light (700–1000 nm) penetrates through human skin up to about 4 mm (Barolet, 2008). Fig. 1c shows a demonstration of the light transmitted through an isolated hand dorsum skin (thickness: ~0.94 mm) from an embalmed human cadaver (race: Asian, ages: 61, male). When the light source (wavelength: 360–2500 nm, AvalightHAL, Avantes) is shined on a spot of the isolated hand dorsum skin, a certain amount of light is transmitted through the skin as can be seen on the white paper (Fig. 1c). By absorbing the transmitted light an implantable photovoltaic (IPV) device can generate electrical power under the skin, and can supply electricity to an implanted medical electronic device, as illustrated in Fig. 1d.
We prepared dual junction solar microcells (GaInP/GaAs), epitaxially grown on GaAs wafers as reported previously (Song et al., 2016). In short, solar microcells (size: 760 µm×760 µm, thickness: 5.7 µm) were fabricated on wafers by the wet etching process (H2O2 30%, H3PO4 85%, HCl 35%, OCI), followed by deposition of electrodes (Ti: 20 nm/ Au: 60 nm). The microcells on the wafers were separated and transferred to a flexible polyimide film (thickness: 12.5 µm) where SU-8 photoresist (thickness: ~2 µm, Microchemicals) was spin-coated to serve as an adhesion layer. The flexible solar microcells array, expected to have long lifetime (~30 years) (Núñez et al., 2013), was encapsulated with multiple transparent layers such as SU-8 (thickness: ~2 µm) and NOA61 (thickness: ~23 µm, Norland Products), also known to be biocompatible (Nemani et al., 2013; Norland product, 2014), to prevent interaction between the solar materials and biological substances, after interconnecting the solar microcells in series (×2) and parallel (×7) with sputtered metal layers (Ti: 50 nm/Au: 300 nm). The encapsulation layers isolate the IPV devices from substances in tissues but transmit light to the devices, thus enabling power generation by photoelectric effect without chemical interactions between the IPV devices and tissue substances. 2.2. Preparation of human cadavers A total of 10 human cadavers (race: Asian, age: 43–95, male: 5, female: 5) were selected for the analysis of solar cell arrays under human skin (Fig. S1). The cadavers were all of Korean descent and had been bequeathed to Chonnam National University Medical School under the acquisition terms described in the Human Tissue Act 1964. The cadavers had been preserved by anatomical embalming using formalin.
3.2. Characteristic of electrical parameters of flexible IPV device under the human skin The current-voltage characteristics of the solar microcells under the human skin are evaluated using a flexible IPV device (Fig. 2a) prepared by transfer-printing and interconnecting thin solar microcells (14 cells, 2 in series and 7 in parallel, thickness: ~5.7 µm) on a flexible polyimide (PI) film (12.5 µm), followed by encapsulating the devices as reported elsewhere (Song et al., 2016). See more details in Material and
2.3. Measuring thickness of human skin The thickness of isolated human skin samples from the cadavers 2
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
Fig. 1. Light transmission through human skin. (a) An image of a human arm, showing the approximate location selected for the shoulder skin sample. (b) A histological microscope image of the stained shoulder skin tissue (epidermis: ~32 µm, dermis: ~1.8 mm) isolated from a fixed human cadaver. (c) Demonstration of light (wavelength: 360–2500 nm) transmission through the isolated hand dorsum skin (thickness: ~0.94 mm) of a fixed cadaver. (d) A schematic illustration of electrical power generation and supply using an implantable photovoltaic (IPV) device, operated by absorbing light transmitted through human skin.
Fig. 2. Electrical properties of the flexible IPV device under the human skin. (a) An optical image of the thin flexible IPV device bent on a forearm with a radius of ~3 mm. (b) An image of the fixed human hand dorsum skin (thickness: ~0.68 mm) which covers the flexible IPV device (red dotted). The electrical properties are measured by probing the exposed square metal pads connected to the IPV device. (c) Current-voltage (I-V) curves of the IPV device when not covered (black line) and when covered (blue line) with the human hand dorsum skin under AM 1.5G illumination. (d) Electrical characteristics of the IPV device when uncovered, and when covered, i.e., under the human skin. The efficiency (η) and short circuit current density (Jsc) of the IPV device decrease from 21.5% to 4.3% and from 5.63 mA/cm2 to 1.17 mA/cm2, respectively. The open circuit voltage (Voc: 4.6 V→4.5 V) and fill factor (FF: 0.83→ 0.84) do not show any significant change under the human skin. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
3
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
(red square, R: 177 ± 4.79 [2.7], G: 165 ± 5.42 [3.28], B: 124 ± 6.51 [5.26]) compared to a hand dorsum (pink triangle, R: 139 ± 6.29 [4.51], G: 120 ± 7.4 [6.19], B: 85 ± 7.27 [8.54]) and chest skin (green circle, R: 129 ± 5.76 [4.47], G: 99 ± 6.89 [6.97], B: 50 ± 7.35 [14.79]) as seen in Fig. 3e. This indicates that the IPV device generates higher electrical power under a bright skin. The skin tone is dominantly determined by distribution of melanin pigment that absorbs ultraviolet and visible light (Igarashi et al., 2007) in the epidermis. Dark skin has higher distribution of melanin pigment, lowering light delivered to the IPV device. Fig. 3f shows the average power densities generated under the skin samples taken from the six locations. The IPV device under the relatively thin skin from the hand dorsum (2.21 mW/cm2) and the upper inner arm (2.34 mW/cm2) generates higher average power, while the lowest power is generated under the thicker forehead skin (0.96 mW/cm2).
methods. The IPV device is covered with human hand dorsum skin isolated from a cadaver (race: Asian, age: 82, male) fixed for preservation, and probed using the exposed metal pads that are connected with the solar microcells under the skin, as shown in Fig. 2b. Under standard AM1.5G illumination (100 mW/cm2, LCS-100, Oriel Instruments), the current-voltage characteristics (Fig. 2c) change from the black line (uncovered means the IPV device is not covered by the skin) to the blue line (under human skin, i.e., the IPV device is covered by the skin) because the intensity of the transmitted light is reduced by the skin. The conversion efficiency (η, red) and short-circuit current density (Jsc, green) decrease from 21.5% to 4.3% and from 5.63 mA/ cm2 to 1.17 mA/cm2, respectively, as seen in Fig. 2d. The open-circuit voltage (Voc, blue) and fill factor (FF, magenta) remain similarly under the human skin (Voc: 4.6 V→4.5 V, FF: 0.83→0.84) because Voc and FF are determined by the properties of the solar materials (Khanna et al., 2013; Vandewal et al., 2008).
3.4. Optical properties of human skin and electrical power of IPV device under non-fixed human skin
3.3. Electrical power of IPV device under human skin from fixed cadavers
The transmittance of the human skin was found to be closely related to the power generated by the IPV device under the skin. Fig. 4a shows the apparatus used to measure the transmittance of the isolated human skin samples. When light guided through an optical fiber from the light source illuminates the isolated human skin, the transmitted light is collected by the lower integrating sphere and quantified with a fiber-optic Spectrometer (Avaspec-ULS2048L, Avantes). More details are in the Material and methods. As expected, the average transmittance (N=9) of the human skin from the hand dorsum (green line) and the upper inner arm (red line) are higher than those of the other skin samples, as shown in Fig. 4b. The transmittance of the thicker skin from the shoulder and forehead are relatively lower as indicated by the magenta and light blue lines, respectively. Measurements using fresh (non-fixed) skin can provide more practical results since fresh, e.g., non-fixed, human skin is closer to live skin than fixed samples, which are denatured and become opaque through the embalming process (Jagdeo et al., 2012; Tabaac et al., 2013). Fig. 4c shows the optical images for fresh (non-fixed) forehead skin (front and back) acquired from a cadaver (race: Asian, age: 95, female) within 26 h after death that did not go through an embalming process. The fresh skin is apparently brighter. Although the thickness of the fresh skin (green square) is comparable to that of the fixed human skin (red circle, hand dorsum (mean ± standard deviation [relative standard deviation (%)]: 0.845 ± 0.196 [23.25] mm), upper inner arm (0.951 ± 0.335 [35.23] mm), antecubitis (0.926 ± 0.151 [16.3] mm), shoulder (1.475 ± 0.414 [28.07] mm) and forehead (1.408 ± 0.393 [27.91] mm)) as seen in Fig. 4d, the transmittance of the fresh human skin is higher than the skin from fixed cadavers. The fresh upper inner arm skin transmits about 20–40% (wavelength: 500– 600 nm) and 50% (wavelength: 600–900 nm) of the incident light, as shown in Fig. 4e. The slight drop in transmittance at wavelengths of ~540 nm and ~580 nm is caused by the absorption of light by hemoglobin (Giangreco et al., 2013; Saka et al., 2010). The substances in capillaries of live human skin may affect the electrical properties of the IPV devices, for example, by absorbing the incident light through skin (Igarashi et al., 2007). Fig. 4f shows the power density of the IPV device under fresh and fixed human skin. Although there is no significant difference in thickness between the fresh and fixed skin samples, the power densities under the fresh skin are much higher (hand dorsum: 8.47 mW/cm2, upper inner arm: 9.05 mW/cm2) because the transmittance of the fresh skin is higher. The electrical power generated by the IPV device under human skin is comparable with those of the previous reports by using flexible piezoelectric devices (0.12–0.18 μW/cm2) (Dagdeviren et al., 2014) or using glucose biofuel cells (0.2–1.3 mW/cm2) (Zebda et al., 2013, 2011), and is enough to operate currently available medical electronic implants such as pacemakers [10–40 μW (Haeberlin et al., 2015)] or implantable cardiac
The amount of electrical power generated under the human skin depends on the thickness and tone of the skin. To evaluate the electrical properties of the IPV device under different types of human skin, we isolated skin samples from 6 different parts of the upper body, namely, the hand dorsum, upper inner arm, antecubitis, chest, shoulder and forehead of 9 human cadavers (total: 54 skin samples, race: Asian, age: 43–82, male: 5, female: 4) that had been preserved with an embalming solution, as shown in Fig. 3a. These samples were selected after considering that most medical electronic implants such as pacemakers, implantable cardioverter defibrillators, vagus nerve stimulators and deep brain stimulators, are inserted in the upper body. Fixed human skin is apparently more opaque, as shown with the images taken from one cadaver (race: Asian, age: 82, male) in Fig. 3a, because the embalming process denatures the skin (Tabaac et al., 2013). More details for each cadaver are presented in Fig. S1. Since the isolated skin samples are very soft, we measured the thickness of the skin while pressing the skin gently with a flat square plate (size: 6 mm×6 mm) at a pressure (81.6 mN/cm2) provided by a motorized translational microstage (resolution: 0.037 µm) and monitored by a force sensor (maximum error: 49 μN, transducer techniques) as shown in Fig. 3b. Fig. 3c shows the measured thickness (n=9) of the isolated skin from the hand dorsum (mean ± standard deviation: 0.845 ± 0.196 mm), from the upper inner arm (0.951 ± 0.335 mm), antecubitis (0.926 ± 0.151 mm), chest (1.179 ± 0.320 mm), shoulder (1.475 ± 0.414 mm) and forehead (1.408 ± 0.393 mm). The electrical power generated by the IPV device covered with the different human skin samples (total 54 skin samples: 6 skin samples×9 cadavers) under standard test conditions (AM1.5G, 100 mW/cm2) was found to be inversely proportional to the skin thickness, as illustrated by the fitting line (black, p=1694/t) in Fig. 3d. The power densities depend on the amount of light delivered to the IPV device through human skin. Thicker skin consisting of keratinocytes, fibroblasts, collagen fibers and many others has more chances to absorb or scatter incident light, thus, reducing light delivered to the IPV device, resulting in lower power density. In addition, under skin samples that have similar thickness (marked with circles), the power density also depends on the skin tone, as shown with the optical images in Fig. 3d. Even with similar skin thickness (~1036 µm, marked with the circles), the IPV device generates different amounts of electrical power under the skin from an upper inner arm (red square, 3.58 mW/cm2), hand dorsum (pink triangle, 1.58 mW/cm2) and chest (green circle, 0.95 mW/cm2), as the skin tones appear to be different. The skin tones were quantified at 30 points using images taken by a camera (5D, Canon) in the same setting and ambient light, and it was determined that the red-greenblue (RGB) intensity (mean ± standard deviation [relative standard deviation (%)]) of the skin from the upper inner arm was the highest 4
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
Fig. 3. Electrical performance of the IPV device under human skin samples isolated from various parts of the body. (a) Optical images of the human skin isolated from 6 different parts of one fixed cadaver (race: Asian, age: 82, male). Skin samples from 9 fixed cadavers (race: Asian, ages: 43–82, male: 5, female: 4) were used in the analysis. (b) Experimental setup to measure the thickness of the human skin samples under consistent pressure (81.6 mN/cm2) with the force sensor mounted on a motorized translational stage (resolution: 0.037 µm). (c) Measured skin thickness (n=9) of the 6 different parts separated from 9 fixed cadavers. (d) Power density of the IPV device under 54 (6 skin samples×9 cadavers) human skin samples with respect to thickness. The power density by the IPV device is inversely proportional to the thickness of the skin because of higher light absorption of thicker skin. Under skin samples with similar thickness (~1036 µm, marked with circles), the power densities of the IPV device are different when the skin tones are different (optical images). (e) RGB intensity (a.u.) of the skin samples having similar thickness (~1036 µm). The intensity is maximum with white (R, G, B: 255) and minimum with black (R, G, B: 0). (f) Measurement results of power densities (mean ± standard deviation, n=9) of the IPV device under the skin samples from 6 different parts of 9 fixed cadavers. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)
5
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
Fig. 4. Optical properties of human skin, and conversion efficiencies of the IPV device under fresh (non-fixed) skin. (a) Experimental setup to measure the transmittance of the human skin. The light source illuminates the skin (inset image) and the transmitted light is collected through the optical cables. (b) Measurements results (n=9, mean) of the transmittance through fixed skin samples. (c) An optical image of the front (left) and back (right) of a fresh skin sample isolated from the forehead of a cadaver (female, Asian, age: 95) without embalming, within 26 h after death. The fresh skin is apparently more transparent and brighter, compare to the fixed skin for preservation. (d) The thicknesses of the fresh (green) and fixed skin samples (red) used for transmittance measurements. (e) The transmittance of the fresh skin is relatively higher compared to the ones from the fixed cadavers. (f) Power densities of the IPV device under the fresh and fixed human skin. Under the fresh skin the IPV device (5.62–9.05 mW/cm2) generates higher electric power than under the fixed skin (0.96–2.34 mW/cm2: hand dorsum (mean ± standard deviation [relative standard deviation (%)]:2.21 ± 1.13 [51.01] mW/cm2), upper inner arm (2.34 ± 0.73 [31.06] mW/cm2), antecubitis (1.89 ± 0.53 [27.95] mW/cm2), shoulder (1.13 ± 0.4 [35.58] mW/cm2) and forehead (0.96 ± 0.59 [61.52] mW/cm2)). (g) Demonstration of power generation with the LEDintegrated IPV device under the human hand dorsum skin. The IPV device under the skin generates electricity and turns on the LED (Inset). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
defibrillators [10 μW (Kim et al., 2016)]. Fig. 4g shows a demonstration using the IPV device under the human dorsum skin, which turns on a LED integrated with the IPV device.
The electrical power density generated under isolated human skin samples by the flexible solar microcells is in the range of sub-to several milliwatts per square centimeter, although the power density depends on skin thickness and tone. Further studies with greater numbers of fresh human skin samples can help statistically estimate the electrical performance of implanted solar microcell arrays with respect to race, age, gender and other factors. The effort to provide sustainable electrical power to devices implanted in the human body should not only reduce the necessity of periodic surgical intervention, but also
4. Conclusions The results reported here provide important information for practically designing and realizing subdermally implantable solar microcell arrays to sustainably power medical electronic implants. 6
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
http://dx.doi.org/10.1109/JPHOTOV.2013.2270348. Kim, D.-H., Viventi, J., Amsden, J.J., Xiao, J., Vigeland, L., Kim, Y.-S., Blanco, J.A., Panilaitis, B., Frechette, E.S., Contreras, D., Kaplan, D.L., Omenetto, F.G., Huang, Y., Hwang, K.-C., Zakin, M.R., Litt, B., Rogers, J.A., 2010. Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat. Mater. 9, 511–517. http://dx.doi.org/10.1038/nmat2745. Kim, S., Ho, J.S., Chen, L.Y., Poon, A.S.Y., 2012. Wireless power transfer to a cardiac implant. Appl. Phys. Lett. 101, 073701. http://dx.doi.org/10.1063/1.4745600. Kim, S.H., Yu, C.H., Ishiyama, K., 2016. Rotary-type electromagnetic power generator using a cardiovascular system as a power source for medical implants. IEEE/ASME Trans. Mechatron. 21, 122–129. http://dx.doi.org/10.1109/TMECH.2015.2436910. Ko, H., Kapadia, R., Takei, K., Takahashi, T., Zhang, X., Javey, A., 2012. Multifunctional, flexible electronic systems based on engineered nanostructured materials. Nanotechnology 23, 344001. http://dx.doi.org/10.1088/0957-4484/23/34/344001. Kurtz, S.M., Ochoa, J.A., Lau, E., Shkolnikov, Y., Pavri, B.B., Frisch, D., Greenspon, A.J., 2010. Implantation trends and patient profiles for pacemakers and implantable cardioverter defibrillators in the United States: 1993–2006. PACE Pacing Clin. Electrophysiol. 33, 705–711. http://dx.doi.org/10.1111/j.1540-8159.2009.02670.x. Kuzum, D., Takano, H., Shim, E., Reed, J.C., Juul, H., Richardson, A.G., de Vries, J., Bink, H., Dichter, M.A., Lucas, T.H., Coulter, D.A., Cubukcu, E., Litt, B., Park, D.-W., Schendel, A.A., Mikael, S., Brodnick, S.K., Richner, T.J., Ness, J.P., Hayat, M.R., Atry, F., Frye, S.T., Pashaie, R., Thongpang, S., Ma, Z., Williams, J.C., 2014. Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications. Nat. Commun. 5, 5258. http://dx.doi.org/10.1038/ ncomms6258. Labroo, P., Cui, Y., 2013. Flexible graphene bio-nanosensor for lactate. Biosens. Bioelectron. 41, 852–856. http://dx.doi.org/10.1016/j.bios.2012.08.024. Liu, C., Alwarappan, S., Chen, Z., Kong, X., Li, C.Z., 2010. Membraneless enzymatic biofuel cells based on graphene nanosheets. Biosens. Bioelectron. 25, 1829–1833. http://dx.doi.org/10.1016/j.bios.2009.12.012. Manunza, I., Bonfiglio, A., 2007. Pressure sensing using a completely flexible organic transistor. Biosens. Bioelectron. 22, 2775–2779. http://dx.doi.org/10.1016/ j.bios.2007.01.021. Mayberg, H.S., Lozano, A.M., Voon, V., McNeely, H.E., Seminowicz, D., Hamani, C., Schwalb, J.M., Kennedy, S.H., 2005. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660. http://dx.doi.org/10.1016/j.neuron.2005.02.014. Minev, I.R., Musienko, P., Hirsch, A., Barraud, Q., Wenger, N., Moraud, E.M., Gandar, J., Capogrosso, M., Milekovic, T., Asboth, L., Torres, R.F., Vachicouras, N., Liu, Q., Pavlova, N., Duis, S., Larmagnac, A., Vörös, J., Micera, S., Suo, Z., Courtine, G., Lacour, S.P., 2015. Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163. http://dx.doi.org/10.1126/science.1260318. Murakawa, K., Kobayashi, M., Nakamura, O., Kawata, S., 1999. A wireless near-infrared energy system for medical implants: a less invasive method for supplying light power to implant devices. IEEE Eng. Med. Biol. Mag. 18, 70–72. http://dx.doi.org/ 10.1109/51.805148. Nemani, K.V., Moodie, K.L., Brennick, J.B., Su, A., Gimi, B., 2013. In vitro and in vivo evaluation of SU-8 biocompatibility. Mater. Sci. Eng. C 33, 4453–4459. http:// dx.doi.org/10.1016/j.msec.2013.07.001. Norland product, 2014. USP Class VI NOA 61 [WWW Document]. URL 〈https://www. norlandprod.com/UV-news.asp〉 Núñez, N., González, J.R., Vázquez, M., Algora, C., Espinet, P., 2013. Evaluation of the reliability of high concentrator GaAs solar cells by means of temperature accelerated aging tests. Prog. Photovolt. Res. Appl. 21, 1104–1113. http://dx.doi.org/10.1002/ pip. Reeder, J., Kaltenbrunner, M., Ware, T., Arreaga-Salas, D., Avendano-Bolivar, A., Yokota, T., Inoue, Y., Sekino, M., Voit, W., Sekitani, T., Someya, T., 2014. Mechanically adaptive organic transistors for implantable electronics. Adv. Mater. 26, 4967–4973. http://dx.doi.org/10.1002/adma.201400420. Reese, R., Gruber, D., Schoenecker, T., Bäzner, H., Blahak, C., Capelle, H.H., Falk, D., Herzog, J., Pinsker, M.O., Schneider, G.H., Schrader, C., Deuschl, G., Mehdorn, G.M., Kupsch, A., Volkmann, J., Krauss, J.K., 2011. Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation. Mov. Disord. 26, 691–698. http://dx.doi.org/10.1002/mds.23549. Romero, E., Warrington, R.O., Neuman, M.R., 2009. Energy scavenging sources for biomedical sensors. Physiol. Meas. 30, R35–R62. http://dx.doi.org/10.1088/09673334/30/9/R01. Saka, M., Berwick, J., Jones, M., 2010. Linear superposition of sensory-evoked and ongoing cortical hemodynamics. Front. Neuroenerg. 2, 195–207. http://dx.doi.org/ 10.3389/fnene.2010.00023. Sardarzadeh, S., 2012. An implantable electrical stimulator for phrenic nerve stimulation. J. Biomed. Sci. Eng. 5, 141–145. http://dx.doi.org/10.4236/ jbise.2012.53018. Song, K., Han, J.H., Lim, T., Kim, N., Shin, S., Kim, J., Choo, H., Jeong, S., Kim, Y.-C., Wang, Z.L., Lee, J., 2016. Subdermal Flexible solar cell arrays for powering medical electronic implants. Adv. Healthc. Mater. 5, 1572–1580. http://dx.doi.org/10.1002/ adhm.201600222. Tabaac, B., Goldberg, G., Alvarez, L., Amin, M., Shupe-Ricksecker, K., Gomez, F., 2013. Bacteria detected on surfaces of formalin fixed anatomy cadavers. Ital. J. Anat. Embryol. 118, 1–5. http://dx.doi.org/10.13128/IJAE-12860. Tahir, Z.M., Alocilja, E.C., Grooms, D.L., 2005. Polyaniline synthesis and its biosensor application. Biosens. Bioelectron., 1690–1695. http://dx.doi.org/10.1016/ j.bios.2004.08.008. Torres, E.O., Rincón-Mora, G.A., 2009. Electrostatic energy-harvesting and batterycharging CMOS system prototype. IEEE Trans. Circuits Syst. I Regul. Pap. 56, 1938–1948. http://dx.doi.org/10.1109/TCSI.2008.2011578. Vandewal, K., Gadisa, A., Oosterbaan, W.D., Bertho, S., Banishoeib, F., Van Severen, I.,
accelerate the development of multi-functional medical implants that can monitor and assist internal organs. Acknowledgements This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B4012854) and the GIST-Caltech Research Collaboration Project through a grant provided by GIST. Appendix A. Supplementary material Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.bios.2016.10.095. References Agnes, C., Holzinger, M., Le Goff, A., Reuillard, B., Elouarzaki, K., Tingry, S., Cosnier, S., 2014. Supercapacitor/biofuel cell hybrids based on wired enzymes on carbon nanotube matrices: autonomous reloading after high power pulses in neutral buffered glucose solutions. Energy Environ. Sci. 7, 1884–1888. http://dx.doi.org/ 10.1039/C3EE43986K. Amar, A. Ben, Kouki, A.B., Cao, H., 2015. Power approaches for implantable medical devices. Sensors. http://dx.doi.org/10.3390/s151128889. Bai, P., Zhu, G., Lin, Z.H., Jing, Q., Chen, J., Zhang, G., Ma, J., Wang, Z.L., 2013. Integrated multilayered triboelectric nanogenerator for harvesting biomechanical energy from human motions. ACS Nano 7, 3713–3719. http://dx.doi.org/10.1021/ nn4007708. Barolet, D., 2008. Light-emitting diodes (LEDs) in dermatology. Semin. Cutan. Med. Surg. 27, 227–238. http://dx.doi.org/10.1016/j.sder.2008.08.003. Carmo, J.P., Goncalves, L.M., Correia, J.H., 2010. Thermoelectric microconverter for energy harvesting systems. IEEE Trans. Ind. Electron. 57, 861–867. http:// dx.doi.org/10.1109/TIE.2009.2034686. Chow, A.Y., Chow, V.Y., Packo, K.H., Pollack, J.S., Peyman, G. a., Schuchard, R., 2004. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch. Ophthalmol. 122, 460–469. http://dx.doi.org/10.1001/ archopht.122.4.460. Cigaina, V., 2004. Long-term follow-up of gastric stimulation for obesity: the Mestre 8year experience. Obes. Surg. 14 (Suppl. 1). http://dx.doi.org/10.1007/BF03342133. Copeland, J.G., Smith, R.G., Arabia, F.A., Nolan, P.E., Sethi, G.K., Tsau, P.H., McClellan, D., Slepian, M.J., 2004. Cardiac replacement with a total artificial heart as a bridge to transplantation. N. Engl. J. Med. 351, 859–867. http://dx.doi.org/10.1056/ NEJMoa040186. Dagdeviren, C., Yang, B.D., Su, Y., Tran, P.L., Joe, P., Anderson, E., Xia, J., Doraiswamy, V., Dehdashti, B., Feng, X., Lu, B., Poston, R., Khalpey, Z., Ghaffari, R., Huang, Y., Slepian, M.J., Rogers, J.A., 2014. Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proc. Natl. Acad. Sci. USA 111, 1927–1932. http://dx.doi.org/10.1073/pnas.1317233111. Fassbender, H., Mokwa, W., Gortz, M., Trieu, K., Urban, U., Schmitz-Rode, T., Gottsche, T., Osypka, P., 2008. Fully implantable blood pressure sensor for hypertonic patients. Proc. IEEE Sens., 1226–1229. http://dx.doi.org/10.1109/ ICSENS.2008.4716664. Giangreco, G.J., Campbell, D., Cowan, M.J., 2013. A 32-year-old female with AIDS , Pneumocystis jiroveci Pneumonia , and Methemoglobinemia. Case Rep. Crit. Care 2013. http://dx.doi.org/10.1155/2013/980589. Goto, K., Nakagawa, T., Nakamura, O., Kawata, S., 2001. An implantable power supply with an optically rechargeable lithium battery. IEEE Trans. Biomed. Eng. 48, 830–833. http://dx.doi.org/10.1109/10.930908. Haeberlin, A., Zurbuchen, A., Schaerer, J., Wagner, J., Walpen, S., Huber, C., Haeberlin, H., Fuhrer, J., Vogel, R., 2014. Successful pacing using a batteryless sunlightpowered pacemaker. Eurospace 16, 1534–1539. http://dx.doi.org/10.1093/ europace/euu127. Haeberlin, A., Zurbuchen, A., Walpen, S., Schaerer, J., Niederhauser, T., Huber, C., Tanner, H., Servatius, H., Seiler, J., Haeberlin, H., Fuhrer, J., Vogel, R., 2015. The first batteryless, solar-powered cardiac pacemaker. Heart Rhythm 12, 1317–1323. http://dx.doi.org/10.1016/j.hrthm.2015.02.032. Hannan, M.A., Mutashar, S., Samad, S.A., Hussain, A., 2014. Energy harvesting for the implantable biomedical devices: issues and challenges. Biomed. Eng. OnLine 13, 79. http://dx.doi.org/10.1186/1475-925X-13-79. Igarashi, T., Nishino, K., Nayar, S.K., 2007. The appearance of human skin: a survey. Found. Trends Comput. Graph. Vis. 3, 1–95. http://dx.doi.org/10.1561/ 0600000013. Jagdeo, J.R., Adams, L.E., Brody, N.I., Siegel, D.M., 2012. Transcranial red and near infrared light transmission in a cadaveric model. PLoS One 7, e47460. http:// dx.doi.org/10.1371/journal.pone.0047460. Katz, E., MacVittie, K., 2013. Implanted biofuel cells operating in vivo – methods, applications and perspectives – feature article. Energy Environ. Sci. 6, 2791–2803. http://dx.doi.org/10.1039/c3ee42126k. Khanna, A., Mueller, T., Stangl, R.A., Hoex, B., Basu, P.K., Aberle, A.G., 2013. A fill factor loss analysis method for silicon wafer solar cells. IEEE J. Photovolt. 3, 1170–1177.
7
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
implantable glucose biosensor based on an epoxy-enhanced polyurethane membrane. Biosens. Bioelectron. 21, 2275–2282. http://dx.doi.org/10.1016/ j.bios.2005.11.002. Zebda, A., Cosnier, S., Alcaraz, J.-P., Holzinger, M., Le Goff, A., Gondran, C., Boucher, F., Giroud, F., Gorgy, K., Lamraoui, H., Cinquin, P., 2013. Single glucose biofuel cells implanted in rats power electronic devices. Sci. Rep. 3, 1516. http://dx.doi.org/ 10.1038/srep01516. Zebda, A., Gondran, C., Le Goff, A., Holzinger, M., Cinquin, P., Cosnier, S., 2011. Mediatorless high-power glucose biofuel cells based on compressed carbon nanotube-enzyme electrodes. Nat. Commun. 2, 370. http://dx.doi.org/10.1038/ ncomms1365. Zhao, Y., Deng, P., Nie, Y., Wang, P., Zhang, Y., Xing, L., Xue, X., 2014. Biomoleculeadsorption-dependent piezoelectric output of ZnO nanowire nanogenerator and its application as self-powered active biosensor. Biosens. Bioelectron. 57, 269–275. http://dx.doi.org/10.1016/j.bios.2014.02.022.
Lutsen, L., Cleij, T.J., Vanderzande, D., Manca, J.V., 2008. The relation between open-circuit voltage and the onset of photocurrent generation by charge-transfer absorption in polymer: fullerene bulk heterojunction solar cells. Adv. Funct. Mater. 18, 2064–2070. http://dx.doi.org/10.1002/adfm.200800056. Wang, J., 2006. Electrochemical biosensors: towards point-of-care cancer diagnostics. Biosens. Bioelectron. 21, 1887–1892. http://dx.doi.org/10.1016/j.bios.2005.10.027. Wood, M.A., Ellenbogen, K.A., 2002. Cardiac pacemakers from the patient's perspective. Circulation 105, 2136–2138. http://dx.doi.org/10.1161/ 01.CIR.0000016183.07898.90. Xu, L., Gutbrod, S.R., Ma, Y., Petrossians, A., Liu, Y., Webb, R.C., Fan, J.A., Yang, Z., Xu, R., Whalen, J.J., Weiland, J.D., Huang, Y., Efimov, I.R., Rogers, J.A., 2015. Materials and fractal designs for 3D multifunctional integumentary membranes with capabilities in cardiac electrotherapy. Adv. Mater 27, 1731–1737. http://dx.doi.org/ 10.1002/adma.201405017. Yu, B., Long, N., Moussy, Y., Moussy, F., 2006. A long-term flexible minimally-invasive
8
Contents lists available at ScienceDirect
Biosensors and Bioelectronics journal homepage: www.elsevier.com/locate/bios
Generation of electrical power under human skin by subdermal solar cell arrays for implantable bioelectronic devices Kwangsun Songa,b, Jung Hyun Hanc,d, Hyung Chae Yange, Kwang Il Namf, Jongho Leea,b,
⁎
a School of Mechanical Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea b Research Institute for Solar and Sustainable Energies, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea c School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea d Haenam Beautis Skin and Laser Clinic, 456-1 Haeri Haenam-gun, Jeollanamdo, 536-809, Republic of Korea e Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Republic of Korea f Department of Anatomy, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Republic of Korea
A R T I C L E I N F O
A BS T RAC T
Keywords: Solar cell Implantable Medical electronic implants Energy Human skin Bioelectronic devices
Medical electronic implants can significantly improve people's health and quality of life. These implants are typically powered by batteries, which usually have a finite lifetime and therefore must be replaced periodically using surgical procedures. Recently, subdermal solar cells that can generate electricity by absorbing light transmitted through skin have been proposed as a sustainable electricity source to power medical electronic implants in bodies. However, the results to date have been obtained with animal models. To apply the technology to human beings, electrical performance should be characterized using human skin covering the subdermal solar cells. In this paper, we present electrical performance results (up to 9.05 mW/cm2) of the implantable solar cell array under 59 human skin samples isolated from 10 cadavers. The results indicate that the power densities depend on the thickness and tone of the human skin, e.g., higher power was generated under thinner and brighter skin. The generated power density is high enough to operate currently available medical electronic implants such as pacemakers that require tens of microwatt.
1. Introduction As the average human lifespan continues to gradually increase, diverse medical electronic implants are becoming more important, to functionally assist internal organs, and to help maintain quality of life by treating chronic diseases. Cardiovascular, neurological and gastroenteric disorders are now being treated by implants, using devices such as cardiac pacemakers (Kurtz et al., 2010), deep brain stimulators (Mayberg et al., 2005), gastric stimulators (Cigaina, 2004) and diaphragmatic stimulators (Sardarzadeh, 2012). However, since the electrical capacity of the batteries which provide power to these medical electronic implants is finite, the batteries are usually large, occupying about half of the volume of the implants (Romero et al., 2009). In addition, the entire implant, including the battery, needs to be periodically replaced every 2–8 years through surgical intervention (Reese et al., 2011; Wood and Ellenbogen, 2002), which creates psychological, physical and financial burdens to patients (Kurtz et al.,
⁎
2010). At the same time, the finite electrical capacity that can be implanted in human bodies limits not only the practical use of mechanically sophisticated flexible and stretchable electronics (Kim et al., 2010; Ko et al., 2012; Labroo and Cui, 2013; Manunza and Bonfiglio, 2007; Reeder et al., 2014) for biomedical applications but is also insufficient for more advanced functionalities, such as real-time communication. Such devices require sustainable high electric power, for example, in advanced therapeutic and diagnostic medical implants including real-time glucose or blood pressure monitors (Fassbender et al., 2008; Yu et al., 2006), bio-signal sensors (Xu et al., 2015), drug delivery systems (Minev et al., 2015), artificial hearts (Copeland et al., 2004) and many others (Chow et al., 2004; Kuzum et al., 2014; Tahir et al., 2005; Wang, 2006). Recently, various energy harvesting strategies have been designed to make use of energy sources in the human body, including electrochemical reactions (Agnes et al., 2014; Katz and MacVittie, 2013; Liu et al., 2010), mechanical motion (Bai et al., 2013; Zhao et al., 2014), wireless energy transmission (Kim et al., 2012) and
Corresponding author. E-mail address: [email protected] (J. Lee).
http://dx.doi.org/10.1016/j.bios.2016.10.095 Received 4 August 2016; Received in revised form 10 October 2016; Accepted 31 October 2016 Available online xxxx 0956-5663/ © 2016 Elsevier B.V. All rights reserved.
Please cite this article as: Song, K., Biosensors and Bioelectronics (2016), http://dx.doi.org/10.1016/j.bios.2016.10.095
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
was measured under constant pressure on a motorized translational microstage equipped with a force sensor (transducer techniques) and top vacuum holder. To accomplish this, first, we adjusted the parallel alignment of the microstage and the top vacuum holder by using a twoaxis tilting stage. The force sensor and a square plate (size: 6 mm×6 mm) were installed on the motorized microstage and the top vacuum holder, respectively. After mounting a skin sample on the flat sensing plate of the force sensor, we slowly moved the microstage (resolution of z-axis: ~0.037 µm) vertically while monitoring the pressure in real time. We measured the thickness of the human skin sample when the applied pressure to the skin was 81.6 mN/cm2.
others (Carmo et al., 2010; Torres and Rincón-Mora, 2009). Some of these methods require further development to improve durability, biocompatibility or electric power output. Another alternative approach involves producing electricity from light transmitted through the skin by photoelectric effect (Amar et al., 2015; Goto et al., 2001; Hannan et al., 2014; Murakawa et al., 1999). Rigid solar cells, implanted into pig models, were found capable of supplying enough power to operate custom-built implants (Haeberlin et al., 2015, 2014). Subdermal flexible solar microcell arrays designed to be mechanically more compatible with skin also generated electricity to power electronic implants in mouse models (Song et al., 2016). Although these studies demonstrated the feasibility of the concept in animal models, the actual electrical characteristics under human skin must be considered in order to further develop the technology for human beings, since the performance of the device can depend on various features of the skin covering the solar cells. Here, we present the electrical performance of flexible implantable photovoltaic (IPV) devices under isolated human skin samples, whose results improve the chances for more realistic use of the implantable power source for human beings. Experiments conducted with skin samples from 6 locations of 10 human cadavers provide quantitative data for the factors (such as skin thickness and tone) that affect the amount of power generation under skin. Results indicate that the IPV devices under the human skin generate around 0.51–9.05 mW/cm2 depending on the thickness and tone of the skin. These results should be very important consideration in designing the sustainable power source for functional medical electronic implants.
2.4. Measuring optical properties of human skin We measured the optical properties of the isolated human skin samples with a fiber-optic spectrometer (Avantes) integrated with double integrating spheres. The double integrating spheres collect scattering light transmitted through translucent skin. We measured the amount of light transmitted (Ms) through human skin placed between the double integrating spheres, for wavelengths of 400– 900 nm. After removing the skin from between the spheres, we repeated the measurements with the light source on (Mw) and off (Md). The transmittance of the human (Ts) skin was calculated using the following equation: Ts=(Ms−Md)/(Mw−Md). We averaged 20 sets of measurements for each skin sample. 3. Results and discussion
2. Material and methods
3.1. Concept of the subcutaneously implantable solar cell for power generation in human body
2.1. Fabrication of flexible IPV device Fig. 1 illustrates the concepts involved in the subcutaneous implantation of solar microcells for electric power generation in human bodies. Since human skin (Fig. 1a) protects our bodies from bacteria, viruses and many other unwanted substances, delivering electrical power to medical electronic implants through electrical wires penetrating the skin may put the body at risk of infection. Generating the necessary electrical power under the skin can avoid that risk. Fig. 1b shows a histological microscope image of shoulder skin, separated from a human cadaver (race: Asian, ages: 82, male) that was preserved by an embalming solution composed of ethanol, glycerin, formalin, phenol and distilled water, and stained with Accustain trichrome stain (Masson) kit (Sigma-Aldrich). The shoulder skin consists of three primary layers: the epidermis (~32 µm), dermis (~1.8 mm) and subcutaneous fat. Although human skin is not optically transparent, a fraction of light (700–1000 nm) penetrates through human skin up to about 4 mm (Barolet, 2008). Fig. 1c shows a demonstration of the light transmitted through an isolated hand dorsum skin (thickness: ~0.94 mm) from an embalmed human cadaver (race: Asian, ages: 61, male). When the light source (wavelength: 360–2500 nm, AvalightHAL, Avantes) is shined on a spot of the isolated hand dorsum skin, a certain amount of light is transmitted through the skin as can be seen on the white paper (Fig. 1c). By absorbing the transmitted light an implantable photovoltaic (IPV) device can generate electrical power under the skin, and can supply electricity to an implanted medical electronic device, as illustrated in Fig. 1d.
We prepared dual junction solar microcells (GaInP/GaAs), epitaxially grown on GaAs wafers as reported previously (Song et al., 2016). In short, solar microcells (size: 760 µm×760 µm, thickness: 5.7 µm) were fabricated on wafers by the wet etching process (H2O2 30%, H3PO4 85%, HCl 35%, OCI), followed by deposition of electrodes (Ti: 20 nm/ Au: 60 nm). The microcells on the wafers were separated and transferred to a flexible polyimide film (thickness: 12.5 µm) where SU-8 photoresist (thickness: ~2 µm, Microchemicals) was spin-coated to serve as an adhesion layer. The flexible solar microcells array, expected to have long lifetime (~30 years) (Núñez et al., 2013), was encapsulated with multiple transparent layers such as SU-8 (thickness: ~2 µm) and NOA61 (thickness: ~23 µm, Norland Products), also known to be biocompatible (Nemani et al., 2013; Norland product, 2014), to prevent interaction between the solar materials and biological substances, after interconnecting the solar microcells in series (×2) and parallel (×7) with sputtered metal layers (Ti: 50 nm/Au: 300 nm). The encapsulation layers isolate the IPV devices from substances in tissues but transmit light to the devices, thus enabling power generation by photoelectric effect without chemical interactions between the IPV devices and tissue substances. 2.2. Preparation of human cadavers A total of 10 human cadavers (race: Asian, age: 43–95, male: 5, female: 5) were selected for the analysis of solar cell arrays under human skin (Fig. S1). The cadavers were all of Korean descent and had been bequeathed to Chonnam National University Medical School under the acquisition terms described in the Human Tissue Act 1964. The cadavers had been preserved by anatomical embalming using formalin.
3.2. Characteristic of electrical parameters of flexible IPV device under the human skin The current-voltage characteristics of the solar microcells under the human skin are evaluated using a flexible IPV device (Fig. 2a) prepared by transfer-printing and interconnecting thin solar microcells (14 cells, 2 in series and 7 in parallel, thickness: ~5.7 µm) on a flexible polyimide (PI) film (12.5 µm), followed by encapsulating the devices as reported elsewhere (Song et al., 2016). See more details in Material and
2.3. Measuring thickness of human skin The thickness of isolated human skin samples from the cadavers 2
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
Fig. 1. Light transmission through human skin. (a) An image of a human arm, showing the approximate location selected for the shoulder skin sample. (b) A histological microscope image of the stained shoulder skin tissue (epidermis: ~32 µm, dermis: ~1.8 mm) isolated from a fixed human cadaver. (c) Demonstration of light (wavelength: 360–2500 nm) transmission through the isolated hand dorsum skin (thickness: ~0.94 mm) of a fixed cadaver. (d) A schematic illustration of electrical power generation and supply using an implantable photovoltaic (IPV) device, operated by absorbing light transmitted through human skin.
Fig. 2. Electrical properties of the flexible IPV device under the human skin. (a) An optical image of the thin flexible IPV device bent on a forearm with a radius of ~3 mm. (b) An image of the fixed human hand dorsum skin (thickness: ~0.68 mm) which covers the flexible IPV device (red dotted). The electrical properties are measured by probing the exposed square metal pads connected to the IPV device. (c) Current-voltage (I-V) curves of the IPV device when not covered (black line) and when covered (blue line) with the human hand dorsum skin under AM 1.5G illumination. (d) Electrical characteristics of the IPV device when uncovered, and when covered, i.e., under the human skin. The efficiency (η) and short circuit current density (Jsc) of the IPV device decrease from 21.5% to 4.3% and from 5.63 mA/cm2 to 1.17 mA/cm2, respectively. The open circuit voltage (Voc: 4.6 V→4.5 V) and fill factor (FF: 0.83→ 0.84) do not show any significant change under the human skin. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
3
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
(red square, R: 177 ± 4.79 [2.7], G: 165 ± 5.42 [3.28], B: 124 ± 6.51 [5.26]) compared to a hand dorsum (pink triangle, R: 139 ± 6.29 [4.51], G: 120 ± 7.4 [6.19], B: 85 ± 7.27 [8.54]) and chest skin (green circle, R: 129 ± 5.76 [4.47], G: 99 ± 6.89 [6.97], B: 50 ± 7.35 [14.79]) as seen in Fig. 3e. This indicates that the IPV device generates higher electrical power under a bright skin. The skin tone is dominantly determined by distribution of melanin pigment that absorbs ultraviolet and visible light (Igarashi et al., 2007) in the epidermis. Dark skin has higher distribution of melanin pigment, lowering light delivered to the IPV device. Fig. 3f shows the average power densities generated under the skin samples taken from the six locations. The IPV device under the relatively thin skin from the hand dorsum (2.21 mW/cm2) and the upper inner arm (2.34 mW/cm2) generates higher average power, while the lowest power is generated under the thicker forehead skin (0.96 mW/cm2).
methods. The IPV device is covered with human hand dorsum skin isolated from a cadaver (race: Asian, age: 82, male) fixed for preservation, and probed using the exposed metal pads that are connected with the solar microcells under the skin, as shown in Fig. 2b. Under standard AM1.5G illumination (100 mW/cm2, LCS-100, Oriel Instruments), the current-voltage characteristics (Fig. 2c) change from the black line (uncovered means the IPV device is not covered by the skin) to the blue line (under human skin, i.e., the IPV device is covered by the skin) because the intensity of the transmitted light is reduced by the skin. The conversion efficiency (η, red) and short-circuit current density (Jsc, green) decrease from 21.5% to 4.3% and from 5.63 mA/ cm2 to 1.17 mA/cm2, respectively, as seen in Fig. 2d. The open-circuit voltage (Voc, blue) and fill factor (FF, magenta) remain similarly under the human skin (Voc: 4.6 V→4.5 V, FF: 0.83→0.84) because Voc and FF are determined by the properties of the solar materials (Khanna et al., 2013; Vandewal et al., 2008).
3.4. Optical properties of human skin and electrical power of IPV device under non-fixed human skin
3.3. Electrical power of IPV device under human skin from fixed cadavers
The transmittance of the human skin was found to be closely related to the power generated by the IPV device under the skin. Fig. 4a shows the apparatus used to measure the transmittance of the isolated human skin samples. When light guided through an optical fiber from the light source illuminates the isolated human skin, the transmitted light is collected by the lower integrating sphere and quantified with a fiber-optic Spectrometer (Avaspec-ULS2048L, Avantes). More details are in the Material and methods. As expected, the average transmittance (N=9) of the human skin from the hand dorsum (green line) and the upper inner arm (red line) are higher than those of the other skin samples, as shown in Fig. 4b. The transmittance of the thicker skin from the shoulder and forehead are relatively lower as indicated by the magenta and light blue lines, respectively. Measurements using fresh (non-fixed) skin can provide more practical results since fresh, e.g., non-fixed, human skin is closer to live skin than fixed samples, which are denatured and become opaque through the embalming process (Jagdeo et al., 2012; Tabaac et al., 2013). Fig. 4c shows the optical images for fresh (non-fixed) forehead skin (front and back) acquired from a cadaver (race: Asian, age: 95, female) within 26 h after death that did not go through an embalming process. The fresh skin is apparently brighter. Although the thickness of the fresh skin (green square) is comparable to that of the fixed human skin (red circle, hand dorsum (mean ± standard deviation [relative standard deviation (%)]: 0.845 ± 0.196 [23.25] mm), upper inner arm (0.951 ± 0.335 [35.23] mm), antecubitis (0.926 ± 0.151 [16.3] mm), shoulder (1.475 ± 0.414 [28.07] mm) and forehead (1.408 ± 0.393 [27.91] mm)) as seen in Fig. 4d, the transmittance of the fresh human skin is higher than the skin from fixed cadavers. The fresh upper inner arm skin transmits about 20–40% (wavelength: 500– 600 nm) and 50% (wavelength: 600–900 nm) of the incident light, as shown in Fig. 4e. The slight drop in transmittance at wavelengths of ~540 nm and ~580 nm is caused by the absorption of light by hemoglobin (Giangreco et al., 2013; Saka et al., 2010). The substances in capillaries of live human skin may affect the electrical properties of the IPV devices, for example, by absorbing the incident light through skin (Igarashi et al., 2007). Fig. 4f shows the power density of the IPV device under fresh and fixed human skin. Although there is no significant difference in thickness between the fresh and fixed skin samples, the power densities under the fresh skin are much higher (hand dorsum: 8.47 mW/cm2, upper inner arm: 9.05 mW/cm2) because the transmittance of the fresh skin is higher. The electrical power generated by the IPV device under human skin is comparable with those of the previous reports by using flexible piezoelectric devices (0.12–0.18 μW/cm2) (Dagdeviren et al., 2014) or using glucose biofuel cells (0.2–1.3 mW/cm2) (Zebda et al., 2013, 2011), and is enough to operate currently available medical electronic implants such as pacemakers [10–40 μW (Haeberlin et al., 2015)] or implantable cardiac
The amount of electrical power generated under the human skin depends on the thickness and tone of the skin. To evaluate the electrical properties of the IPV device under different types of human skin, we isolated skin samples from 6 different parts of the upper body, namely, the hand dorsum, upper inner arm, antecubitis, chest, shoulder and forehead of 9 human cadavers (total: 54 skin samples, race: Asian, age: 43–82, male: 5, female: 4) that had been preserved with an embalming solution, as shown in Fig. 3a. These samples were selected after considering that most medical electronic implants such as pacemakers, implantable cardioverter defibrillators, vagus nerve stimulators and deep brain stimulators, are inserted in the upper body. Fixed human skin is apparently more opaque, as shown with the images taken from one cadaver (race: Asian, age: 82, male) in Fig. 3a, because the embalming process denatures the skin (Tabaac et al., 2013). More details for each cadaver are presented in Fig. S1. Since the isolated skin samples are very soft, we measured the thickness of the skin while pressing the skin gently with a flat square plate (size: 6 mm×6 mm) at a pressure (81.6 mN/cm2) provided by a motorized translational microstage (resolution: 0.037 µm) and monitored by a force sensor (maximum error: 49 μN, transducer techniques) as shown in Fig. 3b. Fig. 3c shows the measured thickness (n=9) of the isolated skin from the hand dorsum (mean ± standard deviation: 0.845 ± 0.196 mm), from the upper inner arm (0.951 ± 0.335 mm), antecubitis (0.926 ± 0.151 mm), chest (1.179 ± 0.320 mm), shoulder (1.475 ± 0.414 mm) and forehead (1.408 ± 0.393 mm). The electrical power generated by the IPV device covered with the different human skin samples (total 54 skin samples: 6 skin samples×9 cadavers) under standard test conditions (AM1.5G, 100 mW/cm2) was found to be inversely proportional to the skin thickness, as illustrated by the fitting line (black, p=1694/t) in Fig. 3d. The power densities depend on the amount of light delivered to the IPV device through human skin. Thicker skin consisting of keratinocytes, fibroblasts, collagen fibers and many others has more chances to absorb or scatter incident light, thus, reducing light delivered to the IPV device, resulting in lower power density. In addition, under skin samples that have similar thickness (marked with circles), the power density also depends on the skin tone, as shown with the optical images in Fig. 3d. Even with similar skin thickness (~1036 µm, marked with the circles), the IPV device generates different amounts of electrical power under the skin from an upper inner arm (red square, 3.58 mW/cm2), hand dorsum (pink triangle, 1.58 mW/cm2) and chest (green circle, 0.95 mW/cm2), as the skin tones appear to be different. The skin tones were quantified at 30 points using images taken by a camera (5D, Canon) in the same setting and ambient light, and it was determined that the red-greenblue (RGB) intensity (mean ± standard deviation [relative standard deviation (%)]) of the skin from the upper inner arm was the highest 4
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
Fig. 3. Electrical performance of the IPV device under human skin samples isolated from various parts of the body. (a) Optical images of the human skin isolated from 6 different parts of one fixed cadaver (race: Asian, age: 82, male). Skin samples from 9 fixed cadavers (race: Asian, ages: 43–82, male: 5, female: 4) were used in the analysis. (b) Experimental setup to measure the thickness of the human skin samples under consistent pressure (81.6 mN/cm2) with the force sensor mounted on a motorized translational stage (resolution: 0.037 µm). (c) Measured skin thickness (n=9) of the 6 different parts separated from 9 fixed cadavers. (d) Power density of the IPV device under 54 (6 skin samples×9 cadavers) human skin samples with respect to thickness. The power density by the IPV device is inversely proportional to the thickness of the skin because of higher light absorption of thicker skin. Under skin samples with similar thickness (~1036 µm, marked with circles), the power densities of the IPV device are different when the skin tones are different (optical images). (e) RGB intensity (a.u.) of the skin samples having similar thickness (~1036 µm). The intensity is maximum with white (R, G, B: 255) and minimum with black (R, G, B: 0). (f) Measurement results of power densities (mean ± standard deviation, n=9) of the IPV device under the skin samples from 6 different parts of 9 fixed cadavers. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)
5
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
Fig. 4. Optical properties of human skin, and conversion efficiencies of the IPV device under fresh (non-fixed) skin. (a) Experimental setup to measure the transmittance of the human skin. The light source illuminates the skin (inset image) and the transmitted light is collected through the optical cables. (b) Measurements results (n=9, mean) of the transmittance through fixed skin samples. (c) An optical image of the front (left) and back (right) of a fresh skin sample isolated from the forehead of a cadaver (female, Asian, age: 95) without embalming, within 26 h after death. The fresh skin is apparently more transparent and brighter, compare to the fixed skin for preservation. (d) The thicknesses of the fresh (green) and fixed skin samples (red) used for transmittance measurements. (e) The transmittance of the fresh skin is relatively higher compared to the ones from the fixed cadavers. (f) Power densities of the IPV device under the fresh and fixed human skin. Under the fresh skin the IPV device (5.62–9.05 mW/cm2) generates higher electric power than under the fixed skin (0.96–2.34 mW/cm2: hand dorsum (mean ± standard deviation [relative standard deviation (%)]:2.21 ± 1.13 [51.01] mW/cm2), upper inner arm (2.34 ± 0.73 [31.06] mW/cm2), antecubitis (1.89 ± 0.53 [27.95] mW/cm2), shoulder (1.13 ± 0.4 [35.58] mW/cm2) and forehead (0.96 ± 0.59 [61.52] mW/cm2)). (g) Demonstration of power generation with the LEDintegrated IPV device under the human hand dorsum skin. The IPV device under the skin generates electricity and turns on the LED (Inset). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
defibrillators [10 μW (Kim et al., 2016)]. Fig. 4g shows a demonstration using the IPV device under the human dorsum skin, which turns on a LED integrated with the IPV device.
The electrical power density generated under isolated human skin samples by the flexible solar microcells is in the range of sub-to several milliwatts per square centimeter, although the power density depends on skin thickness and tone. Further studies with greater numbers of fresh human skin samples can help statistically estimate the electrical performance of implanted solar microcell arrays with respect to race, age, gender and other factors. The effort to provide sustainable electrical power to devices implanted in the human body should not only reduce the necessity of periodic surgical intervention, but also
4. Conclusions The results reported here provide important information for practically designing and realizing subdermally implantable solar microcell arrays to sustainably power medical electronic implants. 6
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
http://dx.doi.org/10.1109/JPHOTOV.2013.2270348. Kim, D.-H., Viventi, J., Amsden, J.J., Xiao, J., Vigeland, L., Kim, Y.-S., Blanco, J.A., Panilaitis, B., Frechette, E.S., Contreras, D., Kaplan, D.L., Omenetto, F.G., Huang, Y., Hwang, K.-C., Zakin, M.R., Litt, B., Rogers, J.A., 2010. Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat. Mater. 9, 511–517. http://dx.doi.org/10.1038/nmat2745. Kim, S., Ho, J.S., Chen, L.Y., Poon, A.S.Y., 2012. Wireless power transfer to a cardiac implant. Appl. Phys. Lett. 101, 073701. http://dx.doi.org/10.1063/1.4745600. Kim, S.H., Yu, C.H., Ishiyama, K., 2016. Rotary-type electromagnetic power generator using a cardiovascular system as a power source for medical implants. IEEE/ASME Trans. Mechatron. 21, 122–129. http://dx.doi.org/10.1109/TMECH.2015.2436910. Ko, H., Kapadia, R., Takei, K., Takahashi, T., Zhang, X., Javey, A., 2012. Multifunctional, flexible electronic systems based on engineered nanostructured materials. Nanotechnology 23, 344001. http://dx.doi.org/10.1088/0957-4484/23/34/344001. Kurtz, S.M., Ochoa, J.A., Lau, E., Shkolnikov, Y., Pavri, B.B., Frisch, D., Greenspon, A.J., 2010. Implantation trends and patient profiles for pacemakers and implantable cardioverter defibrillators in the United States: 1993–2006. PACE Pacing Clin. Electrophysiol. 33, 705–711. http://dx.doi.org/10.1111/j.1540-8159.2009.02670.x. Kuzum, D., Takano, H., Shim, E., Reed, J.C., Juul, H., Richardson, A.G., de Vries, J., Bink, H., Dichter, M.A., Lucas, T.H., Coulter, D.A., Cubukcu, E., Litt, B., Park, D.-W., Schendel, A.A., Mikael, S., Brodnick, S.K., Richner, T.J., Ness, J.P., Hayat, M.R., Atry, F., Frye, S.T., Pashaie, R., Thongpang, S., Ma, Z., Williams, J.C., 2014. Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications. Nat. Commun. 5, 5258. http://dx.doi.org/10.1038/ ncomms6258. Labroo, P., Cui, Y., 2013. Flexible graphene bio-nanosensor for lactate. Biosens. Bioelectron. 41, 852–856. http://dx.doi.org/10.1016/j.bios.2012.08.024. Liu, C., Alwarappan, S., Chen, Z., Kong, X., Li, C.Z., 2010. Membraneless enzymatic biofuel cells based on graphene nanosheets. Biosens. Bioelectron. 25, 1829–1833. http://dx.doi.org/10.1016/j.bios.2009.12.012. Manunza, I., Bonfiglio, A., 2007. Pressure sensing using a completely flexible organic transistor. Biosens. Bioelectron. 22, 2775–2779. http://dx.doi.org/10.1016/ j.bios.2007.01.021. Mayberg, H.S., Lozano, A.M., Voon, V., McNeely, H.E., Seminowicz, D., Hamani, C., Schwalb, J.M., Kennedy, S.H., 2005. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660. http://dx.doi.org/10.1016/j.neuron.2005.02.014. Minev, I.R., Musienko, P., Hirsch, A., Barraud, Q., Wenger, N., Moraud, E.M., Gandar, J., Capogrosso, M., Milekovic, T., Asboth, L., Torres, R.F., Vachicouras, N., Liu, Q., Pavlova, N., Duis, S., Larmagnac, A., Vörös, J., Micera, S., Suo, Z., Courtine, G., Lacour, S.P., 2015. Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163. http://dx.doi.org/10.1126/science.1260318. Murakawa, K., Kobayashi, M., Nakamura, O., Kawata, S., 1999. A wireless near-infrared energy system for medical implants: a less invasive method for supplying light power to implant devices. IEEE Eng. Med. Biol. Mag. 18, 70–72. http://dx.doi.org/ 10.1109/51.805148. Nemani, K.V., Moodie, K.L., Brennick, J.B., Su, A., Gimi, B., 2013. In vitro and in vivo evaluation of SU-8 biocompatibility. Mater. Sci. Eng. C 33, 4453–4459. http:// dx.doi.org/10.1016/j.msec.2013.07.001. Norland product, 2014. USP Class VI NOA 61 [WWW Document]. URL 〈https://www. norlandprod.com/UV-news.asp〉 Núñez, N., González, J.R., Vázquez, M., Algora, C., Espinet, P., 2013. Evaluation of the reliability of high concentrator GaAs solar cells by means of temperature accelerated aging tests. Prog. Photovolt. Res. Appl. 21, 1104–1113. http://dx.doi.org/10.1002/ pip. Reeder, J., Kaltenbrunner, M., Ware, T., Arreaga-Salas, D., Avendano-Bolivar, A., Yokota, T., Inoue, Y., Sekino, M., Voit, W., Sekitani, T., Someya, T., 2014. Mechanically adaptive organic transistors for implantable electronics. Adv. Mater. 26, 4967–4973. http://dx.doi.org/10.1002/adma.201400420. Reese, R., Gruber, D., Schoenecker, T., Bäzner, H., Blahak, C., Capelle, H.H., Falk, D., Herzog, J., Pinsker, M.O., Schneider, G.H., Schrader, C., Deuschl, G., Mehdorn, G.M., Kupsch, A., Volkmann, J., Krauss, J.K., 2011. Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation. Mov. Disord. 26, 691–698. http://dx.doi.org/10.1002/mds.23549. Romero, E., Warrington, R.O., Neuman, M.R., 2009. Energy scavenging sources for biomedical sensors. Physiol. Meas. 30, R35–R62. http://dx.doi.org/10.1088/09673334/30/9/R01. Saka, M., Berwick, J., Jones, M., 2010. Linear superposition of sensory-evoked and ongoing cortical hemodynamics. Front. Neuroenerg. 2, 195–207. http://dx.doi.org/ 10.3389/fnene.2010.00023. Sardarzadeh, S., 2012. An implantable electrical stimulator for phrenic nerve stimulation. J. Biomed. Sci. Eng. 5, 141–145. http://dx.doi.org/10.4236/ jbise.2012.53018. Song, K., Han, J.H., Lim, T., Kim, N., Shin, S., Kim, J., Choo, H., Jeong, S., Kim, Y.-C., Wang, Z.L., Lee, J., 2016. Subdermal Flexible solar cell arrays for powering medical electronic implants. Adv. Healthc. Mater. 5, 1572–1580. http://dx.doi.org/10.1002/ adhm.201600222. Tabaac, B., Goldberg, G., Alvarez, L., Amin, M., Shupe-Ricksecker, K., Gomez, F., 2013. Bacteria detected on surfaces of formalin fixed anatomy cadavers. Ital. J. Anat. Embryol. 118, 1–5. http://dx.doi.org/10.13128/IJAE-12860. Tahir, Z.M., Alocilja, E.C., Grooms, D.L., 2005. Polyaniline synthesis and its biosensor application. Biosens. Bioelectron., 1690–1695. http://dx.doi.org/10.1016/ j.bios.2004.08.008. Torres, E.O., Rincón-Mora, G.A., 2009. Electrostatic energy-harvesting and batterycharging CMOS system prototype. IEEE Trans. Circuits Syst. I Regul. Pap. 56, 1938–1948. http://dx.doi.org/10.1109/TCSI.2008.2011578. Vandewal, K., Gadisa, A., Oosterbaan, W.D., Bertho, S., Banishoeib, F., Van Severen, I.,
accelerate the development of multi-functional medical implants that can monitor and assist internal organs. Acknowledgements This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B4012854) and the GIST-Caltech Research Collaboration Project through a grant provided by GIST. Appendix A. Supplementary material Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.bios.2016.10.095. References Agnes, C., Holzinger, M., Le Goff, A., Reuillard, B., Elouarzaki, K., Tingry, S., Cosnier, S., 2014. Supercapacitor/biofuel cell hybrids based on wired enzymes on carbon nanotube matrices: autonomous reloading after high power pulses in neutral buffered glucose solutions. Energy Environ. Sci. 7, 1884–1888. http://dx.doi.org/ 10.1039/C3EE43986K. Amar, A. Ben, Kouki, A.B., Cao, H., 2015. Power approaches for implantable medical devices. Sensors. http://dx.doi.org/10.3390/s151128889. Bai, P., Zhu, G., Lin, Z.H., Jing, Q., Chen, J., Zhang, G., Ma, J., Wang, Z.L., 2013. Integrated multilayered triboelectric nanogenerator for harvesting biomechanical energy from human motions. ACS Nano 7, 3713–3719. http://dx.doi.org/10.1021/ nn4007708. Barolet, D., 2008. Light-emitting diodes (LEDs) in dermatology. Semin. Cutan. Med. Surg. 27, 227–238. http://dx.doi.org/10.1016/j.sder.2008.08.003. Carmo, J.P., Goncalves, L.M., Correia, J.H., 2010. Thermoelectric microconverter for energy harvesting systems. IEEE Trans. Ind. Electron. 57, 861–867. http:// dx.doi.org/10.1109/TIE.2009.2034686. Chow, A.Y., Chow, V.Y., Packo, K.H., Pollack, J.S., Peyman, G. a., Schuchard, R., 2004. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch. Ophthalmol. 122, 460–469. http://dx.doi.org/10.1001/ archopht.122.4.460. Cigaina, V., 2004. Long-term follow-up of gastric stimulation for obesity: the Mestre 8year experience. Obes. Surg. 14 (Suppl. 1). http://dx.doi.org/10.1007/BF03342133. Copeland, J.G., Smith, R.G., Arabia, F.A., Nolan, P.E., Sethi, G.K., Tsau, P.H., McClellan, D., Slepian, M.J., 2004. Cardiac replacement with a total artificial heart as a bridge to transplantation. N. Engl. J. Med. 351, 859–867. http://dx.doi.org/10.1056/ NEJMoa040186. Dagdeviren, C., Yang, B.D., Su, Y., Tran, P.L., Joe, P., Anderson, E., Xia, J., Doraiswamy, V., Dehdashti, B., Feng, X., Lu, B., Poston, R., Khalpey, Z., Ghaffari, R., Huang, Y., Slepian, M.J., Rogers, J.A., 2014. Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proc. Natl. Acad. Sci. USA 111, 1927–1932. http://dx.doi.org/10.1073/pnas.1317233111. Fassbender, H., Mokwa, W., Gortz, M., Trieu, K., Urban, U., Schmitz-Rode, T., Gottsche, T., Osypka, P., 2008. Fully implantable blood pressure sensor for hypertonic patients. Proc. IEEE Sens., 1226–1229. http://dx.doi.org/10.1109/ ICSENS.2008.4716664. Giangreco, G.J., Campbell, D., Cowan, M.J., 2013. A 32-year-old female with AIDS , Pneumocystis jiroveci Pneumonia , and Methemoglobinemia. Case Rep. Crit. Care 2013. http://dx.doi.org/10.1155/2013/980589. Goto, K., Nakagawa, T., Nakamura, O., Kawata, S., 2001. An implantable power supply with an optically rechargeable lithium battery. IEEE Trans. Biomed. Eng. 48, 830–833. http://dx.doi.org/10.1109/10.930908. Haeberlin, A., Zurbuchen, A., Schaerer, J., Wagner, J., Walpen, S., Huber, C., Haeberlin, H., Fuhrer, J., Vogel, R., 2014. Successful pacing using a batteryless sunlightpowered pacemaker. Eurospace 16, 1534–1539. http://dx.doi.org/10.1093/ europace/euu127. Haeberlin, A., Zurbuchen, A., Walpen, S., Schaerer, J., Niederhauser, T., Huber, C., Tanner, H., Servatius, H., Seiler, J., Haeberlin, H., Fuhrer, J., Vogel, R., 2015. The first batteryless, solar-powered cardiac pacemaker. Heart Rhythm 12, 1317–1323. http://dx.doi.org/10.1016/j.hrthm.2015.02.032. Hannan, M.A., Mutashar, S., Samad, S.A., Hussain, A., 2014. Energy harvesting for the implantable biomedical devices: issues and challenges. Biomed. Eng. OnLine 13, 79. http://dx.doi.org/10.1186/1475-925X-13-79. Igarashi, T., Nishino, K., Nayar, S.K., 2007. The appearance of human skin: a survey. Found. Trends Comput. Graph. Vis. 3, 1–95. http://dx.doi.org/10.1561/ 0600000013. Jagdeo, J.R., Adams, L.E., Brody, N.I., Siegel, D.M., 2012. Transcranial red and near infrared light transmission in a cadaveric model. PLoS One 7, e47460. http:// dx.doi.org/10.1371/journal.pone.0047460. Katz, E., MacVittie, K., 2013. Implanted biofuel cells operating in vivo – methods, applications and perspectives – feature article. Energy Environ. Sci. 6, 2791–2803. http://dx.doi.org/10.1039/c3ee42126k. Khanna, A., Mueller, T., Stangl, R.A., Hoex, B., Basu, P.K., Aberle, A.G., 2013. A fill factor loss analysis method for silicon wafer solar cells. IEEE J. Photovolt. 3, 1170–1177.
7
Biosensors and Bioelectronics xx (xxxx) xxxx–xxxx
K. Song et al.
implantable glucose biosensor based on an epoxy-enhanced polyurethane membrane. Biosens. Bioelectron. 21, 2275–2282. http://dx.doi.org/10.1016/ j.bios.2005.11.002. Zebda, A., Cosnier, S., Alcaraz, J.-P., Holzinger, M., Le Goff, A., Gondran, C., Boucher, F., Giroud, F., Gorgy, K., Lamraoui, H., Cinquin, P., 2013. Single glucose biofuel cells implanted in rats power electronic devices. Sci. Rep. 3, 1516. http://dx.doi.org/ 10.1038/srep01516. Zebda, A., Gondran, C., Le Goff, A., Holzinger, M., Cinquin, P., Cosnier, S., 2011. Mediatorless high-power glucose biofuel cells based on compressed carbon nanotube-enzyme electrodes. Nat. Commun. 2, 370. http://dx.doi.org/10.1038/ ncomms1365. Zhao, Y., Deng, P., Nie, Y., Wang, P., Zhang, Y., Xing, L., Xue, X., 2014. Biomoleculeadsorption-dependent piezoelectric output of ZnO nanowire nanogenerator and its application as self-powered active biosensor. Biosens. Bioelectron. 57, 269–275. http://dx.doi.org/10.1016/j.bios.2014.02.022.
Lutsen, L., Cleij, T.J., Vanderzande, D., Manca, J.V., 2008. The relation between open-circuit voltage and the onset of photocurrent generation by charge-transfer absorption in polymer: fullerene bulk heterojunction solar cells. Adv. Funct. Mater. 18, 2064–2070. http://dx.doi.org/10.1002/adfm.200800056. Wang, J., 2006. Electrochemical biosensors: towards point-of-care cancer diagnostics. Biosens. Bioelectron. 21, 1887–1892. http://dx.doi.org/10.1016/j.bios.2005.10.027. Wood, M.A., Ellenbogen, K.A., 2002. Cardiac pacemakers from the patient's perspective. Circulation 105, 2136–2138. http://dx.doi.org/10.1161/ 01.CIR.0000016183.07898.90. Xu, L., Gutbrod, S.R., Ma, Y., Petrossians, A., Liu, Y., Webb, R.C., Fan, J.A., Yang, Z., Xu, R., Whalen, J.J., Weiland, J.D., Huang, Y., Efimov, I.R., Rogers, J.A., 2015. Materials and fractal designs for 3D multifunctional integumentary membranes with capabilities in cardiac electrotherapy. Adv. Mater 27, 1731–1737. http://dx.doi.org/ 10.1002/adma.201405017. Yu, B., Long, N., Moussy, Y., Moussy, F., 2006. A long-term flexible minimally-invasive
8