EFTA00615029.pdf

Science II AAAS Epidermal Electronics Dae-Hyeong Kim, et al. Science 333, 838 (2011); DOI: 10.1126/science.1206157 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at www.sciencemag.org (this infomation is current as of August 15, 2011): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/333/6044/838.full.html Supporting Online Material can be found at: http://www.sciencemag.org/content/suppl/2011/08/10/333.6044.838. DC1. html http://www.sciencemag.org/content/suppl/2011/08/10/333.6044.838. DC2. html A list of selected additional articles on the Science Web sites related to this article can be found at: http://Www.sciencemag.org/content/333/6044/838.full.html#related This article cites 31 articles, 5 of which can be accessed free: http://www.sciencemag.org/content/333/6044/838.full.html#ref-list-1 This article has been cited by 1 articles hosted by HighWire Press; see: http://i.vww.sciencemag.org/content/333/6044/838.full.html#related-urls This article appears in the following subject collections: Materials Science http://i.vww.sciencemag.org/cgi/collection/mat sci Downloaded from www.sciencemag.org on August 15. 2011 Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2011 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS. EFTA00615029 Epidermal Electronics Dae-Hyeong Kim!' Nanshu Litt' Rui Ma!* Yun-Soung Kim,' Rak-Hwan Kim! Shuodao Wang! Jian Wu,' Sang Min Won,' Hu Tao,` Ahmad Islam,' Ki Jun Yu,' Tae-il Kim,' Raeed Chowdhury, Ming Ying,1 Lizhi Xu,' Ming Li,''` Hyun-Joong Chung' Hohyun Ileum,' Martin McCormick! Ping Liu,s Yong-Wei Zhang,s Fiorenzo G. Omenetto,4 Yonggang Huang,' Todd Coleman! John A. Rogers't We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiologicaL temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller. p hysiological measurement and stimula- tion techniques that exploit interfaces to the skin have been of interest for more than 80 years% beginning in 1929 with electro- encephalography from the scalp (1-3). Nearly all associated device technologies continue, how- ever, to rely on conceptually old designs. Typical- ly, small numbers of bulk electrodes are mounted on the Ain via adhesive tapes, mechanical clamps or straps, or penetrating needles, often medi- ated by conductive gels, with terminal connec- tions to separate boxes that house collections of rigid circuit boards. power supplies, and com- munication components (4-9). These systems have many important capabilities, but they are poorly suited for practical application outside of research labs or clinical settings because of dif- ficulties in establishing long-lived, robust elec- trical contacts that do not irritate the skin and in achieving integrated systems with overall sizes, weights. and shapes that do not cause discom- fort during prolonged use (8, 9). We introduce a different approach. in which the electrodes, elec- tronics. sensors, power supply, and conununi- cation components are configured together into ultrathin, low-modulus, lightweight, stretchable 'Department of Materials Science and Engineering. Beckman Institute for Advanced Science and Technology, and Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana. IL 61801, USA. 'Department of Electrical and Computer Engineering, Coorcinated Science Laboratory, University of dines at Urbana. Champaign, Urbana, IL 61801, USA. 3Department of likchanical Engineering and Department of OW and Environmental Engineering, North- western University. Evanston, IL 60208. USA. `Department of Biome:kcal Engineering, Tufts Unhers*y, Ilsdford. MA 02155, USA. 'Institute of High Performance Computing. 1 Fuslonopotis Way, 016.16 Connexis. 138632, Singapore. EStace Key Lab- oratory of Structural Analysis for Industrial Equipment Dalian University of Technology, Dalian 116024, China. 'These authors contributed equally to this work. tTo whom correspondence should be addressed. E•mait jrogers@uiuc.edu "skin-like" membranes that confomrally lam- inate onto the surface of the skin by soft contact, in a manner that is mechanically invisible to the user, much like a temporary transfer tattoo. Materials, mechanics, and design strategies. A demonstrative platform is shown in Fig. I. integrating a collection of multifunctional sen- sors (such as temperature. strain, and elect:0- physiological), microscale light-emitting diodes (LEDs), active/passive circuit elements (such as transistors, diodes, and resistors), wireless power coils, and devices for radio frequency (RF) com- munications (such as high-frequency inductors, capacitors, oscillators, and antennae). all integrated on the surface of a thin (-30 gm). gas-permeable elastomeric sheet based on a modified polyester (BASF, Ludwigshafet Germany) with low Young's modulus (-60 kPa) (fig. SI A). The devices and interconnects exploit ultrathin layouts (<7 pm), neutral mechanical plane configurations, and op- timized geometrical designs. The active elements use established electronic materials, such as sil- icon and gallium arsenide, in the form of fila- mentary serpentine nanoribbons and micro- and nanomembranes. The resuh is a high-performance system that offers reversible, elastic responses to large strain deformations with effective moduli (<150 kPa), bending stiffnesses (<1 nN m), and areal mass densities (<3.8 mg/cm2) that are or- ders of magnitude smaller than those possible with conventional electronics or even with re- cently explored flexible/stmtchabk device tech- nologies (10-19). Water-soluble polymer sheets [polyvinyl alcohol (PVA) (Aicello, Toyohashi, Japan); Young's modulus, -1.9 GPa; thickness, -50 µm (fig. SIB)] serve as temporary supports for manual mounting of these systems on the skin in an overall construct that is directly anal- ogous to that of a temporary transfer tattoo. The image in Fig. 1B. top, is of a device similar to the one in Fig. IA, after mounting it onto the skin by washing away the PVA and then partially peeling the device back with a pair of tweezers. When completely removed, the system collapses on itself because of its extreme defonnability and skin-like physical properties, as shown in Fig. I B, bottom (movie SI). The schematic illus- tration in the inset shows an approximate cross- sectional layout. These mechanical characteristics lead to ro- bust adhesion to the skin via van der Waals forces alone, without any mechanical fixturing hardware or adhesive tapes. The devices im- pose negligible mechanical or mass loading (typ- ical total mass of —0.09 g), as is evident from the images of Fig. IC, which show the skin de- forming freely and reversibly, without any ap- parent constraints in motion due to the devices. Electronics in this form can even be integrated directly with commercial temporary transfer tat- toos as a substrate alternative to polyester or PVA. The result, shown in Fig. ID. is of possible interest as a way to conceal the active compo- nents and to exploit low-cost materials (the gib- strate, adhesives, and backing layers) already developed for temporary transfer tattoos (movie SI). Potential uses include physiological sta- tus monitoring, wound measurement/tmatment, biological/chemical sensing, human-machine in- terfaces, covert communications, and others. Understanding the mechanics of this kind of device, the mechanophysiology of the skin, and the behavior of the coupled abiotic-biotic system are all important For present purposes, the skin can be approximated as a bilayer, consisting of the epidermis (modulus, 140 to 600 kPa; thick- ness, 0.05 to 1.5 mm) and the dennis (modulus, 2 to 80 kPa; thickness, 0.3 to 3 mm) (20-23). This bilayer exhibits linear elastic response to tensile strains 5.15%, which transitions to non- linear behavior at higher strains, with adverse, irreversible effects beyond 30% (24). The sur- face of the skin has wrinkles, creases, and pits with amplitudes and feature sizes of 15 to 100 pm (25) and 40 to 1000 pm (26). respectively. The devices described here (Fig. I) have moduli, thick- nesses, and other physical properties that are well matched to the epidermis. with the ability to conform to the relief on its surface. We therefore refer to this class of technology as an "epidermal electronic system" (EES). Macroscopically, an EES on skin can be treated as a thin film on an epidermis-dennis bilayer substrate. Microscopically. the sizes of the individual electronic components and intercon- nects are comparable with those of relief features on the skin and therefore must be considered explicitly. We began by considering aspects of adhesion, in the macroscopic limit. Globally. de- tachment can occur in either tension or compres- sion becaum of interfacial cracks that initiate at the edges or the central regions of the EES. re- spectively. Low effective moduli and small thick- nesses minimize the deformation-induced stored elastic energy that drives both of these failure modes. Analytical calculation (27) shows that Downloaded from www.sciencemag.org on August 15, 2011 838 12 AUGUST 2011 VOL 333 SCIENCE www.sciencemag.org EFTA00615030 RESEARCH ARTICLES' compared with silicon chips (thickness of —1 min) and sheets of polyimide (thickness of —75 pm), the driving forces for delamination of the EES/skin interface are reduced by more than seven and four orders of magnitude. respectively. Measure- ments and theoretical calculations (27) shown in Fig. 2A explore the relevant scaling behaviors in structurts that provide simplified, macroscopic models of EES/skin. The experiments use sheets of polyester (-2 mm thick) for the skin and fihns of poly(dimethylsikocane) (PDMS) (Dow Coming, Midland, USA) for the EES. The critical delam- ination strain is plotted in Fig. 2A as a function of PDMS thickness for two different formula- tions: one with a modulus of 19 kPa (50:1) and C D antenna LED doss power coil the other 145 kPa (30:1) (fig. SIC). The results, both theory and experiment, confirm that reduc- ing the modulus and thickness lowers the driv- ing forces for interface delamination for a given applied strain (bending or stretching) without lower bound. The mechanical properties of the EES de- pend on the effective modulus and thickness of both the circuits and sensors and the substrate. In samples such as those in Fig. 1, the properties of the active components and interconnects can dominate the mechanics of the overall system. The in-plane layouts and materials of this layer are therefore key design parameters. Recent work in stretchable electronics establishes that the stria n an' temp. sensor 0.5mm 0.5cm .,„. ii err g11W neat. ler undeformed state loctronics overall range of defonnability can be optimized in systems composed of active devices joined together in open-mesh Am-tures by non-coplanar interconnects in neutral mechanical plane con- figurations, in which elastomers with relative- ly large moduli (2 to 10 MPa) and thicknesses (millimeters to centimeters) serve as substrates (13, 14). For EES, the effective modulus (EEEs) and bending stiffness (E/F.F.$), rather than the range of stretchability. are paramount These It- quiretww. demand alternative designs and chokes of materials. If we assume that the effective moduli of the individual devices (for example, Young's modulus -160 GPa for Si and —90 GPa for GaAs) are much higher than those of the RF coil RF diode ECG/EMG sensor attached to skin !ter partially detach from the skin PI — 4- device 7lint P • PE (-50 Kea) t 301m 4 after fully detach from the akin mm 3mrrt crumpled circuit 4— polyester backside of tattoo after transfer —to after Integration onto skin - to after deformation Fig. 1. (A) mage of a demonstration platform for multifunctional elec- tronics with physical properties matched to the epidermis. Mounting this device on a sacrificial, water-soluble film of PVA, placing the entire structure against the skin, with electronics facing down, and then dissolving the PVA leaves the device conformally attached to the skin through van der Waals forces alone, in a format that imposes negligible mass or mechanical loading effects on the skin. (B) ES partially (top) and fully (bottom) peeled away from the skin. (Inset) A representative cross-sectional illustration of the struc- ture, with the neutral mechanical plane (NMP) defined by a red dashed line. (C) Multifunctional EES on skin: undeformed (left), compressed (middle), and stretched (right). (D) A commercial temporary transfer tattoo provides an alternative to polyester/PVA for the substrate; in this case, the system in- cludes an adhesive to improve bonding to the skin. Images are of the back- side of a tattoo (far left), electronics integrated onto this surface (middle left), and attached to skin with electronics facing down in undeformed (middle right) and compressed (far right) states. encemag.org on August 15, 2011 Downloaded from www. www.sciencemag.org SCIENCE VOL 333 12 AUGUST 2011 839 EFTA00615031 I RESEARCH ARTICLES interconnects and that the interconnected device components (rather than the substrate) dominate the mechanics. then we can write the approxi- mate expression ELEN En(I + Las), where E,„, is the effective modulus of the intercon- nects, Ld is the characteristic device size, and L, is the distance between devices, as illustrated in fig SID. The value of EF.Es can be minimized by reducing E1,,, and L/L... For the former. thin narrow interconnect lines formed into large- amplitude "filamentary serpentine" (FS) shapes represent effective designs. For the latter, ultrathin active devices that adopt similar FS layouts and continuously integrate with FS interconnects reduce the effective value of Ld to zero. The value of E. 1 as decreases rapidly with the thick- nesses of the devices, interconnects, and sub- strate. An ultrathin FS construct is shown in Fig. 2B. left, with a cross-sectional schematic illus- tration as an inset. Results of tensile testing e 60 40 4'20 0.• —•— 50:1 —* c 30:1 theory - Fe x 60 60 co ! it° a. 0 IP • -roe 020 0 0 0 3 0.6 0.9 1.2 1 5 O 0 0 0.5 1.0 1.5 2.0 PDMS thickness (mm) PDMS thickness (mm) (Fig. 213, right) indicate that such FS-EES sam- ples (Fig. 213, left) achieve EE (-140 kPa) and Elms (-03 Witt) (27) that are comparable with the epidermis and more than one and five orders of magnitude smaller than previously reported stretchable electronic devices, respectively (28). Furthermore, highly repeatable loading and un- loading stress-strain curves up to strains of 30% demonstrate purely elastic nsponses, with max- imum principal swains in the metals that are less than -0.2% (fig. SI E). Calculations yield effec- tive tensile moduli (Fig. 2B, right). with excellent correspondence to experiment Such FS layouts can maintain nearly 20% weal contact of active elements with the skin, for effective electrical in- terfaces. In certain applications, layouts that in- volve some combination of Fs geometries and device islands (Ld not equal to zero) connected by FS interconnects (Fig. I and fig. SIF) can be used, with expected consequences on the local 90 ter 9.20 0 230 N 0 0 5 10 15 20 25 30 Strain c9.) D E mechanics (fig. SIG). In both options, suitable designs lead to mechanical and adhesive prop- erties that allow conformal adhesion to the skin and minimal loading effects (Fig. 2C). Without optimized layouts, we observed delamination un- der similar conditions of deformation (fig. Sill), which is consistent with the fracture modes il- lustrated in Fig. 2A. For many uses of EES, physical coupling of devices to the surface of the skin is important. Confocul micrographs of EES mounted on pig skin appear in Fig. 2. D and E, as well as fig. 52C Wye information and bare pig skin confocal mi- crographs am S110 \411 in fig. S2. A and B. respec- tively; sample preparation and imaging procedures can be found in (27)]. With Fs structures, the results show remarkably conformal contact, not only at the polyester regions of the EES but also at the Fs elements (Fig. 2, 13 and E). Similar behavior was obtained, but in a less ideal device 5kin • Fig. 2. (A) Plots of critical tensile (left) and compressive (right) strains for delamination of a test structure consisting of films of PDMS on substrates of polyester, designed to model the EES/skin system. Data for formulations of PDMS with two different moduli are shown (red, 19 kPa; blue, 145 kPa). The critical strains increase as the PDMS thickness and modulus decrease, which is consistent with modeling results (Ones). (B) Optical micrograph of an EES with FS design OK The plot (right) shows the stress-strain data from uniaxial tensile measurements for two orthogonal directions. Data collected from a sample of pig skin are also presented. The dotted lines correspond to calculations performed with finite element modeling. (C) Skin of the forehead before (top left) and after the mounting of a representative FS-EES, at various magnifications and states of deformation. The dashed blue boxes at right highlight the outer boundary of the device. The red arrows indicate the direction of compressive strains generated by a contraction of facial muscles. The red dashed box at the top right corresponds to the field of view of the image in the bottom left. (D) Confocal microscope image (top view) at the vicinity of the contacting interface between an FS-EES laminated on a sample of pig skin. The FS structure and the skin are dyed with red and blue fiuorophores, respectively. (E) Cross-sectional confocal images at locations corresponding to the numbered, white dashed lines shown in the top-view frame above. Downloaded from www.sciencemag.org on August 15, 2011 840 12 AUGUST 2011 VOL 333 SCIENCE www.sciencemag.org EFTA00615032 RESEARCH ARTICLES' fashion (fig. S2C), with layouts that incorporate device islands. These observations are consistent with analytical mechanics treatments that use macroscopic models of the EES and account for microscopic structures on the skin (27). Related calculations suggest that spontaneous pressures created by surface interactions are -ID kPa (fig. SIOB), which is below the sensitivity of human skin (-20 kPa) (29) but still sufficient to offer reasonable adhesion. Microscopic models indi- cate that these interactions generate compressive forces (per unit length) of —0.1 Wm for each FS strip (27). Improved bonding can be achieved by using adhesives that are built into platforms for temporary transfer tattoos, as in Fig. I D. Multifundional operation. A key capability of EES is in monitoring electrophysiological (EP) processes related to activity of the brain (elecuoen- cephalograms (EEGs)], the heart [electrocanlio- grams (ECCrs)] and muscle tissue [electroinyograins (EMGs)J. Amplified sensor electrodes that in- corporate silicon metal oxide semiconductor field effect transistors (MOSFETs) in circuits in which all components adopt FS designs provide de- vices for this purpose. Here, the gate of a FS- MOSFET connects to an extended FS electrode for efficient coupling to the body potential (Fig. A B 1.6 1.2 0.8 0.4 0.0 3A; the inset shows an analogous design based on a rectangular device island and FS intercon- nects) via contact with the skin in a common- source amplifier configuration (Fig. 3B, left). The measured frequency response at different input capacitances (CIN) is indicated in Fig. 3B, right, and is in quantitative agreement with circuit sim- ulations (fig. S3, A and B). The value of CIN is determined by a series combination of capaci- tances of the gate electrode, the encapsulating PI, and junction between the gate electrode and the body surface. The bandwidth matches re- quirements for high-performance EP recording. A typical layout for this purpose includes four am- plified channels, each comprising a FS-MOSFET, a silicon-based FS resistor, and an FS electrode. One channel provides a reference, whereas the others serve as sites for measurement. Results of demonstration experiments appear subsequently. Many other classes of semiconductor devices and sensors are also possible in EES, including resistance-based temperature sensors built with meander electrodes of Pt (Fig. 3C, left, and fig. S3C), in-plane strain gauges based on carbon- black-doped silicones (Fig. 3C, right, and fig. S3D), LEDs and photodetectors based on AlInCraP (for possible use in optical dietetic& 10•3 104 10' 10' 10' Frequency (Hz) Fig. 3. (A) Optical micrographs of an active eledrophysiological (EP) sensor with local amplification, as part of an FS-EES. (Left) The source, drain, and gate of a silicon MOSFET and a silicon feedback resistor before connection to sensor electrodes, all in FS layouts. (Inset) Similar device with island design. (Right) The final device, after metallization for the interconnects and sensor electrodes, with magnified view (inset). (B) Circuit diagram for the amplified EP sensor shown above (left). (Right) Measured and simulated frequency response for different input capacitance = co, 1,uF, 220p0. (C) Optical micrograph of a temperature sensor that uses a platinum resistor with FS interconnects Deft) D E G motion of the sleinthiofluids) (Fig. 3D, left, and fig. S3, E to G), and silicon FS photovohaic cells (Fig. 3D, right). Such cells can generate a few tens of miaowatts (fig. SRI); increasing the a=s or weal coverages can improve the output but not without compromises in size and mechanics. Wire- less powering via inductive effects represents an appealing alternative. An example of an FS induc- tive coil connected to a microscale InGaN LED is shown in Fig, 1E. with electromagnetic model- ing of its RF response. The resonance frequency (-35 MHz) matches that of a separately located transmission coil powered by an external supply. Voltage and cumin outputs in the receiver are mrf- &lent to operate the microscale LEDs remotely. as shown in Fig. 3E. Such coils provide power directly in this example; they can also conceivably be configured to charge future classes of EES- integrated storage capacitors or batteries. Examples of various RF components of the type needed for wireless communications or for scavenging RF energy are presented in Fig. 3, F and G. Shown in Fig. 3F is an optical image of silicon PIN diode (left) and its mall-signal scat- tering parameters (fig S3K), indicating insertion loss (S21 in forward condition) of <6 dB and isolation (S2 I in reverse condition) of >15 dB 2mm C X01 R ',We- it detector • 1 — 1 m m • • F l\AW-1\i N 0.9 LI 0.8 6-0.7 O u- 0.6 Ti 0.5 8 0.4 05 ti 1.0 1.6 2.0 2.6 30 Capacitance (pF) and a strain gauge that uses electrical y conductive silicone (CPDMS; right). (D) Image of an array of microscale AlInGaP LEDs and photodetectors, in an in- terconnected array integrated on skin, under compressive deformation Deft) and of a FS silicon solar cell bight). (0 Image of a FS Wireless coil connected to a microscale InGaN LED, powered by inductive coupling to a separate trans- mission coil (not in the field of view). (F) Optical micrograph of a silicon RF diode. (G) Optical micrograph of an interconnected pair of FS inductors and capacitors designed for RF operation Deft). The graph at right shows resonant frequencies for LC oscillators built with different FS capacitors. Downloaded from www.sciencemag.org on August 15, 2011 www.sciencemag.org SCIENCE VOL 333 12 AUGUST 2011 841 EFTA00615033 I RESEARCH ARTICLES for frequencies of up to 2 Gliz. Examples of FS inductors and capacitors and their RF re- sponses appear in Fig. 3G and fig. S3L. Con- necting pairs of such devices yields oscillators with expected resonant frequencies (Fig. 3G, right). A notable behavior is that the response varies with the state of deformation because of the dependence of the RF inductance on geo- metry. For example, at tensile strains of —12% the resonance frequency shifts by -30°4(4. S3, I and 5). Such effects, which also appear in the wireless power coils but not in the other devices of Fig. 3, will influence the behavior of antenna structures and certain related RF components. These issues must be considered explicitly in EES design and modes of operation. A 52- 200 100 ra. -100 B 5. 100 ci 0 E <-100 C -r7r = 200 U (1) 100 E • 10 L L 0 N X 200 U w • 100 cr E 0 U- ,103 F _31:1 810 O 0 5 5 10 Time (s) ,▪ 200 • 100 ti 0 • 100 Systems for electrophysiological recording. EES configured for measuring ECG, EMG, and EEG in conformal, skin-mounted modes with- out conductive gels or penetrating needles pro- vide imponant, system-level demonstrations (fig. S4A and movie S2) (27). All materials that come into direct contact with the skin (Au, PI, and polyester) are biocompatible (30, 31). Mea- surements involved continuous use for as many as 6 hours. Devices wom for up to 24 hours or more on the arm, neck, forehead, cheek, and chin showed no degradation or irritation to the skin (figs. 514 and S15). Devices mounted in chal- lenging areas such as the elbow fractured and/or debonded under full-range motion (fig. S16). ECG recordings from the chest (27) revealed base V S 15 00 &thy d Erit 100 0 100 5 10 15 20 0 Time (s) 0.2 Time (s) 0.4 cony. 1014 filltyolorn 5 10 15 20 Time (s) walk • .4 stand active 5 10 15 20 walk 4 • r. ti os 1 at • ", stand passive 5 10 Time(s) 10 15 20 25 Frequency (Hz) 15 20 D 260 E 200 Ira ;150 . 1 0 0 LL 150 10 high-quality signals with information on all phases of the heartbeat, including rapid depo- larization of the cardiac wave, and the asso- ciated QRS complex (Fig. 4A, right) (32). EMG measured on the leg (27) with muscle contrac- tions to simulate walking and resting are pre- sented in Fig. 4B, left. The measurements agree remarkably well with signals simultaneously collected using commercial. bulk tin electrodes that require conductive gels, mounted with tapes at the same location (Fig. 4B, right, and fig. S4B, right). An alternative way to view the data (spectrogram) is shown in Fig. 4C, in which the spectral content appears in a color contour plot with frequency and time along the y and .r axes, respectively. Each muscle contraction comsponds up down left right 0 t 2 3 0 1 2 3 0 1 2 3 0 1 2 3 Tima (s) Time(s) Times) Time(s) up ■ 17IIIDIG113, •Ila• IS • ESN • • ICE ■ • ■ Mtn down MERE smile* akiN ■ non •,:•• i ti ir • ••••••• WIN • ■ ■ Men right • I. •••• • • ••_J X Mina ME III Min I I I I left ■ • IMRE ••••••• • MS moist • "U NINE eyes closed eyes open alpha rhythm - r Opening blinking 4 8 12 Time (s) Fig. 4. (A) ECG signals measured with an active EES attached to the chest (left), and magnified view of data corresponding to a single heartbeat (right). (B) (Left) EMG measurements using an active EES, mounted on the right leg during simulated walking (from 0 to 10 s) and standing (from 10 to 20 s). (Right) Recordings collected with conventional sensors and conductive FL (C) Spectrogram of the data in (B) for corresponding electrode type. (D) EMG spectrograms measured using an active EES mounted on the neck during vocalization of four different words: "up," "down," "left," and "right." (B 16 20 /10 • 0 X• 10 20 20 00 0.5 1.0 1.5 Time (s) 2.0 Simulated video game control by pattern recognition on EMG data from (D). The player icon is moved from an initial position (red) to destination (green). (F) (Left) Discrete Fourier transform (DFT) coefficients of EEG alpha rhythms at —10 Hz (27), measured with a passive EES. (Center) The spectrogram of the alpha rhythm. The first and next 10 s correspond to periods when the eyes were dosed and open, respectively. The responses at —10 and —14 s correspond to eye opening and blinking, respectively. (Right) Demonstration of Stroop effects in EEG measured with a passive EES. Downloaded from www.sciencemag.org on August 15, 2011 842 12 AUGUST 2011 VOL 333 SCIENCE www.sciencemag.org EFTA00615034 RESEARCH ARTICLES I to a red, venical stripe that spans from 10 to 300 Hz (32). To demonstrate EMG recording in a mode in which conventional devices are particularly ill suited, an EES mounted on the Oroat r= mon- itor musek activity, noninvasively, during speech (fig. S5A) (27). Tiere, recordimp; collected during vocalization of tour mani; rup," "doswi," "la," and light"), repeated 10 times exit (fig. S6) ex- hibit distindive pattens, as in Fig. 4D. Measure- inents from another set of words ("go," "stop," and "great")(figs. S5B and S7) suggest sufficient structure in the signals for recognizing a vocab- ulary of words. These capabilities mate opportu- nities for EES-based human/midline interfaces. As an example, dynamic time-waming pattem- recognition algorithms applied to throat-based EMG data (Fig. 4D) enable control of a computer strategy game (Sokoban), as illustrated in Fig. 4E. The classifications occur in less than 3 s on a dual-core personal computer running codes in MATLAB (MathVkrics, Natick, MA), with an acduacy of >90% (flg. S8). As a human/machine interface, EEG data offer additional promise. EES mounted on a re- gion of the fort-head diat is first prepared by exfoliating the stratum comeum with Scotch tape yields reproducible, high-quality msults, as dem- onstrated in alpha rhythms recorded from awake subjects with Meir eyes elosed (fig. S9A) (27). The expected feature at —10 Hz appears clearly in the Fouricr-transformed data of Fig. 4F, teft. The spectrogram of Fig. 4F, center. shows similar signatuns. This activity disappeats wiren the eyes are open. The signal-to-noise stios att compa- rable with those obtained in otherwise identical experiments that used conventional, rigid bulk electrods with conductive coupling gols. In fis- ther demonstrations. EEG ineasuted with EES reveals well-known cognitive phenomena such as the Stroop effekt (33,34). In these experiments, subjects randomly presented with congruent or incongment (fig. S9B) colored words whimer the tokn (not the word) as quickly as possible. The data show that the motor responses penain- ing to the whispering are maniftsted by two pet at -650 ms (congruent case) and -1000 ms (in- congnient case), as shows in Fig. 4F, right. The time delsy implies dim the congruent stimuli require fewer cognitive remurces and are quicker to process than are the incongruent ones, which is consistent with the literature (33, 34). Conclusions. The materials and mechanics ideas presented hete enable intimate, mechani- cally "invisible," tight and mliable attachment of high-performance electronic functionality with the surface of the skin in ways that bypass limi- tations of previous approaches. Meny of the EES concepts are fully compatible with small- scale integrated circuits flid can be released from ultrathin-body silicon-on-wafer substrates. For long-term use, materials and device strategies to actommodate the continuous efflux of dead cells from the surface of the skin and the pro- cesses of transpiration will be needed. References and Notes 1. H. Berger, Ardi. Psychiatc Nervenkt 87, 527 (1929). 2. C. D. Hardyck, L F. Petnnovich, D. W. Lilswonh, Science ase, 1067 (1966). 3. E. J. fok R. Meliack, Poul 2, 141 (1976). 4. p. G. Webster. Ed.. Medkal msfromentanon: Applicanon ond Design (Wiley, New York, 2009), pp. 189-240. 5. A. Seiden, L. Kirkup, Physiol. Allas. 21, 271 (2000). 6. P. Griss, H. K. lolvanen-Laakso, P. AierltMnen, G. Stemme, IEEE fram &omet Eng. esi, 597 (2002). 7. L IA.Yu, F. E. H. litt D. G. Guo, L. Ku, K. L Yap, Sens. ACtuOlon A Phys. 151, 17 (2009). 8. B. Geite, 5. Karlsson, 5. Day, Al. Djupsybacka, in Modem lechniques tnNewascience.. U.Windborsi, H. Johansson, Eds. (Sumper Verlag, Berlin, 1999), pp. 705-755. 9. J. R. Ives, 5. Ni. Mesanen, D. Janes, Gin. NeumphysioL 118, 1633 (2007). 10. 1. Selatani er at, Science 321, 1468 (2008). 11. 5. C. 8. Mannslek et at, Not. Matet 9, 859 (2010). 12. K. Takel Mot, Not. Matet 9, 821 (2010). 13. 0.-el. Kim er al, Science 320, 507 (2008). 14. R..H. Kim mat Nat. Matet 9, 929 (2010). 15. M Kuho ez ot, Adv. Matet (Deenfteld Bed& flo.) 22, 2749 (2010). 16. M Gemalen et at, AfictoeWbon. Rebab. 48, 825 (2008). 17. 5. P. Lacour. I. Jones, 5. Wagner, 1. 11, 2. Suo, Proc. IEEE 93, 1459 (2005). 18. C. Keplinger, M. Kallenbrumer, N. Arnold, 5. Bauer, Proc Hatt. Mod. Sd. U.S.A. 107, 4505 (2010). 19. L Hu et at, Nano Lex 10, 708 (2010). 20. 0. Kommi', J. Saothong, N. Yoshikavra, Med. Eng. Phys. 30, 516 (2038). 21. IA. Geengs er at, B10Merh. 44, 1176 (2011). 22. C. Padler-Matte', 5. Be c, H. 2ahouani, Med. Eng. Phys. 30, 599 (2008). 23. httpfidermatobgy.abouticonksrskinanatomytaranatomy. 24. Y.40nioasit MO. flanish.R. Sanleed,1 Blom 19,307(1994). 25. L khvialeva el ot, in Skin Roughness Assessment. New Derelopments ut Siam!~ Engineenng, D. Campok, Ed. (InTech, vnwrintechopen.comMownloadtpdf/pdfs_icV 9090, 2010). 26. K.-P. Wilhelm P. Fliner, E. Beraidema, Bioengsneenng of the Skin: Skin Sulfat ((naging ond Ana s (CRC, Bota Raten, 1997). 27. Matenals and methods are available as suppating material on Science Online. 28. 0..H. Kim er ot, Proc. Natt. Acad. Sd. USA. 105, 18675 (2008). 29. A. Kaneku, N. Mai, T. Kanda, I Hand Mer. IB, 021, guu 025 (2005). 30. K. C. (heting, P. Renaud, H. Tank, K. Djupsund, &Osens. BIONea100. 22, 1783 (2007). 31 M. ot, Ad. kna motet 20, 4069 (2010). 32. L. Sdrnmo, P. Laguna, Moefecrneol Signal Ptacessing M Carthac and Neumlogicol Application (Elsevier, Amsterdam, 2005). 33. J. R. 5I700p, 7 &p. Psychol. 18, 643 (1935). 34. 0. Spleen, E. A. Strauss, Compenditim Aieuropsyrhological fem: Admintsrmeon, NO= ond Corninentat (Oxford Univ. Press, New York, 2006). Acknowledgments: This malenal is based on work suppOrled by a National Secunty Science and Engineering faculty Fellonship and a grant from the Air Fmce Research Laboratory. The manufacturing tedinigues ekre deve4oped end) suppop from the National Science Foundation (NSB under mant EMMI 07.49028 and used fardities at the Materials Research Laboratory and Center for Ibcroanalyus of Materials at the University of Ilheis al Urbana-Champrmk suppested by die U.S. oepanmere of Energy, Lenden of Mathals Sciences under awards DE4G02-07f R46471 and DE4G02-07ER06053. mkncraledges suppen kom a Beckman Institute postdocioral fellonship. Y.H. mkncraledges NSF granis ECCS-0824129 and OISE-1043143. We thank K. Shenoy and R. Nut» for usefuldkcusoms. One ot mc« pionsional parens are bring filedonthisivort.JARasa ro-kunder and eguiry holder m the company MC10, dich punar, the commernalizancn ei beiniemated dewces. Supporting Online Material vAntsciekemag.org(cgikontentrfulU333/6040/838/DC1 Malene(' and Methods Eg,. 51 to 517 References (35-40) Modes 51 and 52 28 Mardi 2011; accepted 10 lune 2011 to.musclenretzerast A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses Damian C. Eldert,1* Robert H. E. Friesen,2 Gira Bhabha,1 Ted Kwaks,2 Mandy Ringeneelen,2 Wenli Ytt?' Carla Ophorst,2 Freek Cox,2 Hans J.W.M. Korse,2 Boerries Brandenburg,2 Ronald Vogels,2 Just P.J. Brakenhof1,2 Ronald Kompier,2f Martin H. Koldijk,z Lisette A.H.M. Comelissen,1 Leo L. M. Poon,4 Malik Peiris,` Wouter Koudstaal,zt Ian A. Wilson,l'st Jaap Goudsmit2 Current flu vattines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies 'hat broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monodonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which rause severe human infection. The dysta( structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stank distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hente, enable development of a universal flu vattine and broad-spectrum antibody therapies. I nfluenza vimses cause millions of cases of severe illoss each year. thousands of deaths, and considerable economic losses. Currently, nyo main countenneasures are used against flu. First, nitall-molecule inhibitors of the neuramin- idast surface glycoprotein and the vial ion chan- nel M2 have been widely used and proven to be quite effective against susceptible strains (i). Flowever, resistance to these antivirals has re- duced Meir effectiveness, and mutations associated with oseltamivir and amantadine are widespread (2-4). The second main countenneasure is vac- cination. Currem vaccinas diai are based on in- activated vimses elicit a potent immune responm Down loaded from www.sciencemag.org on August 15, 2011 www.sciencemag.org SCIENCE VOL 333 12 AUGUST 2011 843 EFTA00615035