www.sciencemag.org/content/350/6258/314/suppl/DC1

Supplementary Materials for

A skin-inspired organic digital mechanoreceptor

Benjamin C.-K. Tee, Alex Chortos, Andre Berndt, Amanda Kim Nguyen, Ariane Tom, Allister McGuire, Ziliang Carter Lin, Kevin Tien, Won-Gyu Bae, Huiliang Wang, Ping Mei,

Ho-Hsiu Chou, Bianxiao Cui, Karl Deisseroth, Tse Nga Ng, Zhenan Bao* *Corresponding author. E-mail: zbao@stanford.edu

Published 16 October 2015, Science 350, 314 (2015) DOI: 10.1126/science.aaa9306

This PDF file includes: Materials and Methods

Figs. S1 to S14

Tables S1 and S2

Caption for movie S1

References

Other supplementary material for this manuscript includes the following: Movie S1

2

Materials and Methods

Ring oscillator fabrication and testing

The organic field-effect transistors are in top-gate geometry and are fabricated on plastic

polyethylene naphthalate foils as described in Refs (15, 16). The electrodes are inkjet printed using

Ag nanoparticle dispersion from Colloidal Ink in Japan. Organic semiconductors from Flexink and

Polyera were inkjet printed to form p-channel and n-channel transistors. The gate dielectric is a

bilayer, comprised of a Teflon layer (from Dupont) next to the semiconducting layer and a high-k

PVDF-TrFE-CTFE relaxor polymer (from Piezotech). All fabrication and measurement are done

in air. We tested the ring oscillator using an active probe and low-input capacitance unity gain

buffer, which was used for interfacing a conventional silicon edge-detector chip with the organic

circuits For optical neuron stimulation, an edge detector circuit was added to obtain a pulse width

of 2 ms. With continuous stimulation, the neurons fire at their natural frequency (~300 Hz).

Consequently, the pulse width must be smaller than the inverse of this frequency (3.3 ms) to avoid

producing multiple action potentials with one oscillation of the oscillator. Therefore, the edge

detector was necessary to ensure the desired property of producing one action potential per

oscillation of the sensor. The complete circuit diagram is included as Fig. S14. The buffer and edge

detector circuits are conventional silicon chips, but in future versions, it could be straightforward

to eliminate the buffer and monolithically integrate the oscillator and edge detector on one substrate

to have a fully printed organic digital e-skin.

Piezoresistive sensor fabrication

Single-walled carbon nanotubes (CNTs) were obtained from Carbon Solutions, Inc. (P2-SWNT).

10 mg of CNTs were dispersed in NMP by sonicating for 30 minutes using a tip horn sonicator

(Cole Parmer ultrasonic processor 750 W) at 30% power. The resulting solution was centrifuged

at 8000 RPM for 30 minutes using a Sorvall Lynx 4000 centrifuge. The solution was spraycoated

onto a silicon wafer at 200°C to form a conducting electrode. A solution of polyurethane

elastomer (SG80A from Lubrizol) was spincoated onto the electrode. The electrode was

subsequently transferred onto a polyurethane substrate. To form the piezoresistive composite, 20

mg of CNTs in 9 mL of chloroform were dispersed by sonicating for 20 minutes at 30% power.

After adding 1 mL of a 10 mg/mL solution of poly-3-hexylthiophene (Sepiolid P100), the

solution was sonicated for another 60 minutes, and was subsequently centrifuged for 20 minutes

at 6000 RPM. The dispersed CNTs were mixed with a solution of polyurethane (SG80A from

Lubrizol) in chloroform and spincoated onto PDMS molds of pyramid structures. The CNT

electrodes were laminated on top of the piezoresistive pyramids and heated at 60°C for 5 minutes

to ensure good bonding. The CNT electrode/piezoresistive composite stack was then removed

from the mold. As the counter electrodes, we used evaporated gold on glass slides as rigid

electrodes or spraycoated silver nanowires (AW060 from Zhejiang Kechuang Advanced

Materials Technology Co., Ltd.) embedded in PDMS as stretchable electrodes.

Mutagenesis of iC1C2(s/v) and testing in cultured neurons

DNA sequence of n-terminal modified C1C2 version bC1C2 was synthesized (Genescript) and

cloned into AAV vectors containing the CamKIIα promoter for expression in neurons. The

construct was fused to eYFP DNA (enhanced yellow fluorescent protein) to detect protein

expression in neurons by fluorescence microscopy. Mutations (I170V and Q95S) were introduced

using QuickChangeTM Site-Directed mutagenesis kit (Agilent). Plasmid DNA was purified with

QIAprepTM Spin Miniprep Kits (Qiagen) after transformation and amplification in E. coli.

3

Electrophysiological recordings in neuronal cultures were prepared as described(27). Patch pipettes

(4-6 MΩ) were pulled from glass capillaries (Sutter Instruments) with a horizontal puller (P-2000,

Sutter Instruments) for whole-cell recordings in voltage and current clamp. Recordings were made

using a MultiClamp700B amplifier (Molecular Devices). The external recording solution contained

(in mM): 127 NaCl, 10 KCl, 10 HEPES, 2 CaCl2, 2 MgCl2, 30 D-glucose, pH 7.3, including

synaptic blockers (25 µM D-APV, 10 µM NBQX). The patch pipette solution contained (in mM):

140 K-gluconate, 10 HEPES, 10 EGTA, 2 MgCl2, pH 7.3. Series resistance was monitored

throughout recordings for stability. A Spectra X Light engine (Lumencor) was used to excite eYFP

and to apply light for opsin activation. Stimulation light (475 nm) was applied through a 40X

objective (Olympus) at 5 mW/mm2 light intensity. Photocurrents were measured at -80 mV in

voltage clamp mode during 1 s light application. All reported values refer to the stationary

photocurrents. The activation spectra for bC1C2(s/v) and ChR2(HR) were measured by recording

stationary photocurrent in voltage clamp mode at -80 mV and light intensities of 0.65 mW/mm2 at

each wavelength. Light was delivered through 20 nm bandbass filters (Thorlabs) at (in nm): 400,

420, 440, 460, 480, 500, 520, 540, 560, 580, 600. Photocurrents were normalized to 480 nm.

Kinetics of channel closure were determined by fitting the decay of photocurrents after light-off,

with mono-exponential or bi-exponential functions. Channel kinetics were quantified by

corresponding tauoff values respectively. pClamp10.3 (Molecular Devices) and OriginLab8

(OriginLab) software was used to record and analyze data.

Stereotactic virus injection

The following adeno-associated viruses (AAV) with serotype DJ were produced at the Stanford

Neuroscience Gene Vector and Virus Core: double floxed AAVdj-EF1a-DIO::ChR2(E123A)-

EYFP and AAVdj-EF1a-DIO::bC1C2(s/v)-EYFP 4-6 week old PV+-IRES-Cre mice were injected

bilaterally with 1 µl of either virus in the medial prefrontal cortex (mPFC) or the primary

somatsensory cortex forelimb region (S1FL), at the following coordinates (from bregma): AP +1.7

mm, ML +0.3 mm, DV -2.5 mm (mPFC) or AP +0.26 mm, ML +2.1 mm, DV -1.5 mm (S1FL).

Titer were matched at 1.5x1012 vg/ml for both viruses. Expression is controlled by Cre-recombinase

and restricted to parvalbumin positive cells (PV+). Expression is controlled by Cre-recombinase

and restricted to parvalbumin positive cells (PV+).

Acute slice electrophysiology

Acute brain slices were prepared from mouse medial prefrontal cortex (mPFC) or primary

somatsensory cortex forelimb region (S1FL) 4-6 weeks after viral injection. Coronal slices (300

μm) from injected mice were prepared after intracardial perfusion with ice-cold, sucrose-containing

artificial cerebrospinal fluid solution (ACSF; in mM): 85 NaCl, 75 sucrose, 2.5 KCl, 25 glucose,

1.25 NaH2PO4, 4 MgCl2, 0.5 CaCl2 and 24 NaHCO3. Slices recovered for 1 hour at 32–34 °C, and

then were transferred to an oxygenated recording ACSF solution (in mM): 123 NaCl, 3 KCl, 26

NaHCO3, 2 CaCl2, 1 MgCl2, 1.25 NaH2PO4 and 11 glucose, at room temperature.

Electrophysiological recordings were performed at 32–34 °C under constant perfusion of the

oxygenated recording ACSF solution. For mPFC recordings, synaptic transmission blockers (D-2-

amino-5-phosphonovaleric acid (APV; 25 μM), 2,3-dihydroxy-6-nitro-7-sulfamoyl-

benzo[f]quinoxaline-2,3-dione (NBQX; 10 μM) and gabazine (10 μM)) were added to the

recording ACSF solution. Slices were visualized with an upright microscope (BX61WI, Olympus)

under infrared differential interference contrast (IR-DIC) optics. A Spectra X Light engine

(Lumencor) was used both for viewing fluorescent protein expression and delivering light pulses

for opsin activation. PV+ neurons were identified by eYFP+ expression. Whole-cell voltage-clamp

recordings were performed at -80 mV, and current-clamp recordings were performed at rest. Patch-

clamp pipettes contained the following internal solution (in mM): 125 K-gluconate, 10 KCl, 10

HEPES, 4 Mg3-ATP, 0.3 Na-GTP, 10 phosphocreatine, 1 EGTA. Recordings were conducted using

MultiClamp700B amplifier and pClamp10.3 software (Molecular Devices). pClamp10.3,

4

OriginLab8 (OriginLab), and SigmaPlot (SPSS) were used to analyze data. Stationary photocurrent

of the opsins was measured at the end of a 1-s light pulse (475 nm) in voltage-clamp mode. Light-

evoked spike probability in the PV+ neurons was calculated as the fraction of successful action

potentials evoked in neurons at light stimulation frequencies ranging from 40 to 200 Hz during a 4

second stimulation period.

Electrical neuron stimulation with inorganic oscillators

Prior to cell plating, multi-electrode arrays (MEAs) were cleaned with a brief oxygen plasma and

coated with 200 μg/mL poly-L-lysine. Hippocampal [or cortical] neurons were isolated from E18

rats and cultured for 10-14 days on MEAs as previously described. The neurons were maintained

in neurobasal medium supplemented with B27, penicillin/streptomycin, and L-glutamine.

Electrical activity of primary neuron cultures was stimulated by an external stimulation

macroelectrode (to achieve spatial control) and recorded by planar (Multi-electrode arrays) MEAs.

The stimulating macroelectrode was connected to a pulse generator, which was in turn connected

to the DiTact sensor. Commercial signal processing and amplification were used (Multichannel

Systems) to record both stimuli and evoked cellular responses.

5

DiTact sensor characterization

Fig. S1. Images of organic ring oscillators. (A) Array of printed complementary ring oscillators.

Zoomed-in area shows the 3-stage ring oscillator. Each oscillator pixel is composed of three

inverters that form the oscillator and one additional inverter that functions as a buffer. The

oscillators near the top of the substrate are five stage oscillators and the ones near the bottom of the

substrate are three-stage oscillators (B) Voltage output of a three-stage ring oscillator showing a

frequency of 110 Hz at a supply voltage of 8V.

6

Fig. S2. Electrical characteristics of p- and n-type transistors in the complementary organic

oscillators. (A) Transfer curves and (B) output curves for p-type devices. P-type devices had a W/L

of 42 and a mobility of 0.10 cm2V-1s-1. (C) Transfer curves and (D) output curves for n-type devices.

N-type devices had a W/L of 60 and a mobility of 0.07 cm2V-1s-1.

7

Pressure Sensor Characterization

Fig. S3. Effect of pyramid size on the pressure response of piezoresistive sensors. Small

pyramids (3 μm) have higher sensitivity, but smaller dynamic range. 50 μm pyramids have the

desired sensing properties throughout the pressure range of interest. The voltage was 5 V.

8

Fig. S4. Effect of pyramid spacing on the pressure response of the piezoresistive sensors. As

the spacing between pyramids increases, the sensitivity increases. However, when pyramids are

spaced far apart, the region between the pyramids comes in contact with the substrate, preventing

recovery to the initial impedance. The pressure at which device characteristics become

irrecoverable decreases as pyramid spacing increases. With a spacing of 50 μm, the device

properties are recoverable throughout the measurement range. With a spacing of 100 μm,

irrecoverable deformation occurs at ~40 kPa, and with a spacing of 200 μm, irrecoverable

deformation occurs at only 20 kPa. The voltage was 5 V.

10

Figure S4. Effect of pyramid spacing on the pressure response of the piezoresistive sensors. As the

spacing between pyramids increases, the sensitivity increases. However, when pyramids are spaced

far apart, the region between the pyramids comes in contact with the substrate, preventing recovery

to the initial impedance. The pressure at which device characteristics become irrecoverable

decreases as pyramid spacing increases. With a spacing of 50 μm, the device properties are

recoverable throughout the measurement range. With a spacing of 100 μm, irrecoverable

deformation occurs at ~40 kPa, and with a spacing of 200 μm, irrecoverable deformation occurs at

only 20 kPa. The voltage was 5 V.

9

Fig. S5. Voltage dependence of the sensor impedance. The voltage dependence can be

approximated as exponential (R2 > 0.98).

Data Fitting for Sensor Pressure Dependence

The sensors function partially based on changes in the tunneling barrier as a function of

pressure. Tunneling current density is substantially influenced by the applied voltage.

Consequently, the pressure sensor characteristics are voltage-dependent. This is important for the

DiTact sensor because in a voltage divider configuration, the voltage across the piezoresistor

changes with applied pressure, resulting in a complex relationship between the pressure and voltage

dependence. Fig. S6 depicts the voltage dependence and fitted characteristics of a model sensor.

10

Fig. S6: Experimental and fitted sensor impedance. (A) Dependence of the impedance of the

sensor on the pressure and voltage. (B) Fitted value of the impedance as a function of pressure and

voltage. The fitting process gave an R2 value of 0.975. (C) The log value of the residuals from the

fitting process.

The magnitude of the impedance can be modeled using equation (1), where Zsensor is the

impedance of the sensor, P is the pressure, Vsensor is the voltage across the sensor, and a1 to a5 are

parameters to be fit to the data. The electric field dependence of tunneling currents from CNT

electrodes can often be approximated by an exponential fit(28, 29). The impedance of a

piezoresistive sensor based on tunneling depends exponentially on the applied strain(30).

Consequently, the pressure dependence is determined by the stress-strain behavior of the device.

11

The deviation from exponential behavior caused by the shape of the pyramids is taken into account

by the exponent on the pressure term (a4).

𝑍𝑠𝑒𝑛𝑠𝑜𝑟 = 𝑎110^(𝑎2𝑉𝑠𝑒𝑛𝑠𝑜𝑟 + 𝑎3𝑃𝑎4) (1)

The circuit diagram for the sensing element is show in Fig. S7. The reference resistor is not

necessary in the device, but can be useful for tuning the pressure response characteristics (Fig. S9).

Therefore, in addition to the piezoresistive composite composition and the structure of the pyramids

in the piezoresistive sensor, the reference resistor adds another method of modifying the device

output. Tunable characteristics are important because mechanoreceptors in different parts of the

body have different saturation frequencies, different sensitivities, and different shapes of the

frequency vs stimulus curves(18).

Equation (2) provides the voltage across the oscillator which is the supply voltage of the

oscillator. The fitted equation for the impedance of the sensor (1) can be substituted into the

equation for the voltage across the oscillator (2), resulting in a non-linear implicit equation for the

dependence of Vosc on the applied pressure. Furthermore, as shown in Fig. 1c, the impedance

through the oscillator is also voltage-dependent. The resulting equation was solved using MATLAB

to determine the voltage across the sensor and the oscillator for each pressure value. The pressure

and the voltage across the sensor and the impedance of the sensor for the fitted data from Fig. 2c

are plotted in Fig. S8.

𝑉𝑜𝑠𝑐 =[𝑍𝑜𝑠𝑐

−1 +𝑍𝑟𝑒𝑠𝑖𝑠𝑡𝑜𝑟−1 ]

−1

[𝑍𝑜𝑠𝑐−1 +𝑍𝑟𝑒𝑠𝑖𝑠𝑡𝑜𝑟

−1 ]−1

+ 𝑍𝑠𝑒𝑛𝑠𝑜𝑟𝑉𝑎𝑝𝑝𝑙𝑖𝑒𝑑 (2)

12

Fig. S7. Circuit diagram used for calculating pressure dependence. The voltage dependence of

the pressure sensor characteristics as well as the voltage dependence of the oscillator impedance

must be taken into account to accurately predict the frequency of the sensor.

13

Fig. S8. Sensor voltage fit during pressure test. Fitted values of the impedance of the pressure

sensor and the voltage across the sensor as a function of pressure for the circuit shown in fig. S7

without a resistor (resistor with infinite impedance).

The modeled electrical properties of the circuit was used to investigate some aspects of the circuit’s

response to pressure. Fig. S6 shows the effect of different reference resistor values on the pressure

dependence of the sensing characteristics.

14

Fig. S9: Effect of reference resistors on frequency output. As the impedance of the reference

resistor decreases, the sensitivity decreases while the working range increases. Furthermore, the

shape of the curve becomes more linear.

15

Channelrhodopsin Protein Characterization

We replaced the first 49 amino acids by the first 11 amino acids of ChR2 to improve membrane

trafficking and expression. As shown before, introduction of the mutation I131V accelerated

channel closure(31), which we further enhanced by replacing glutamine 56 by serine (Q56S).

Fig. S10. bC1C2(v/s) characterization in cultured neurons. (A) Schematic composition of

channelrhodopsin hybrids C1C2 and bC1C2(v/s): Both contain segments from channelrhodopsin 1

and 2 (ChR1 and 2). Numbers indicate amino acid positions. bC1C2(s/v) was mutated at positions

56 (Q56S) and 131 (I131V) to accelerate channel kinetics. The first 39 amino acids were replaced

by the first 11 amino acids of ChR2 to improve expression and membrane trafficking. (B)

Activation spectrum of bC1C2(v/s) (red) compared to ChR2(HR) (black). Each construct n = 3. All

error bars indicate s.e.m., n indicates number of cells. (C) Photocurrents amplitudes -80 mV: ChR2-

H134R (ChR2(HR), n = 24), ChR2-E123A (ChETA(EA), n = 18), C1C2 (n = 18), bC1C2(IV)

(bC1C2(I131V), n = 15) and bC1C2(s/v) (n = 19). (D) Left: tau-values of mono-exponential off-

kinetics (ChR2(HR), ChETA(EA), C1C2) and the fast components of bi-exponential off-kinetics

(C1C2(IV), bC1C2(s/v)). Same n as in (A). Right: Proportion of photocurrent amplitudes decaying

with fast tau-off.

16

17

Fig. S11. Comparison of fast channelrhodopsin bC1C2(v/s) and ChETA(EA) (A) Decay of

photocurrents after 475 nm light excitation (blue bar). Current traces were normalized to compare

speed of channel closures. bC1C2(s/v) (red) off-kinetics are bi-exponential with a fast and slow

component. ChETA(EA) (black) current decays exponentially. (B) Photocurrent amplitudes

measured in cortical parvalbumin positive (PV+), fast spiking interneurons of mice medial

prefrontal cortex (mPFC). ChETA(EA): n = 16, bC1C2(s/v): n = 10. (C) Left: tau-values of mono-

exponential ChETA(EA) off-kinetics and the fast bi-exponential bC1C2(s/v) off-kinetics.

ChETA(EA): n = 16, bC1C2(s/v): n = 10. Right: Proportion of photocurrent amplitudes decaying

with fast and slow tau-off.

18

Fig. S12. Comparison of real and artificial mechanoreceptors. (A) Pressure response of

biological mechanoreceptors in the human foot.(32) Reproduced with permission. (B) Frequency

of action potentials vs pressure for parvalbumin interneurons in the prefrontal cortex coupled to the

DiTact sensor. There is a good correlation in the threshold frequency and maximum frequency. The

first three trials depicted were from different locations on a sample with a CNT content of 1.17

wt%. The fourth trial was conducted using a sensor with a smaller concentration of CNTs and

shows a lower sensitivity. The operation voltage was 8 V, resulting in a max frequency of 130 Hz

and a max power consumption of 4.5 µW. (C) Indentation response of biological mechanoreceptors

in the human fingertip.(33) Reproduced with permission. (D) Frequency of action potentials vs

pressure for neurons in the primary somatosensory cortex coupled to the DiTact sensor. All ten

trials used the same oscillator and sensor. The operation voltage was 11 V, resulting in a max

19

frequency of 200 Hz and a max power consumption of 18.4 µW.

Fig. S13. Electrical stimulation of plated hippocampal neurons.. (A) A ramped pressure from 0

to 100kPa was applied. The stimulation pulse frequency increases proportionally with the pressure

with the neuron firing tracking the stimulation frequency. (B) Three instance of stimulated neuron

firing from tactile sensor. (C) Panel shows a single action potential triggered from a stimulation

pulse due to pressure. An inorganic oscillator was used as the source of oscillation.

20

Fig. S14: Full circuit diagram of the elements used for interfacing the DiTact sensor with the neuron

stimulation equipment. The buffer is a unity gain low-input capacitance node for interfacing

conventional silicon edge-detector chip with organic circuits.

21

Photocurrents

(pA)

± s.e.m / n

tauoff

(ms)

± s.e.m /

n

fast tauoff

(ms)

± s.e.m / n

slow tauoff

(ms)

± s.e.m

% of

photocurrent

w/ fast tauoff

± s.e.m

% of

photocurrent

w/ slow tauoff

± s.e.m

ChR(HR) 868.8

± 79.4 / 24

38.8

± 8.7 / 24

- - - -

ChETA(EA) 657.9

± 72.0 / 18

18.8

± 1.3 / 18

- - - -

C1C2 1212.9

± 129.9 / 18

30.7

± 1.0 / 18

- - - -

bC1C2(IV) 1284.5

± 98.7 / 15

- 14.7

± 0.81 / 15

137.8

± 14.9

88.2

± 0.1

11.8

± 0.1

bC1C2(s/v) 1245.8

± 118.87 / 19

- 8.9

± 0.55 / 19

129.7

± 20.8

87.0

± 0.1

13.0

± 0.1

Supp. Table 1. Biophysical properties of channelrhodopsin variants in cultured neurons of

mouse hippocampus. s.e.m. is standard error of the mean. n indicates number of cells

22

Photocurrents

(pA)

± s.e.m / n

tauoff

(ms)

± s.e.m / n

fast tauoff

(ms)

± s.e.m / n

slow

tauoff

(ms)

± s.e.m

% of

photocurrent

w/ fast tauoff

± s.e.m

% of

photocurrent

w/ slow tauoff

± s.e.m

ChETA(EA) 311.1

± 50.2 / 16

7.0

± 0.3 / 16

- - - -

bC1C2(s/v) 704.1

± 101.1 / 10

- 3.4

± 0.2 / 10

31.2

± 2.0

78.6

± 1.6

21.4

± 1.6

Supp. Table 2. Biophysical properties of ChETA(EA) and bC1C2(s/v) in cultured neurons

of mouse hippocampus. s.e.m. is standard error of the mean. n indicates number of cells.

23

Movie S1

The movie shows the flexible DiTact sensors mounted on a wearable glove. At zero pressure stimuli, the sensor outputs no digital signal. The glove was used to apply pressure on a digital weighing scale. The output from the monitor shows the frequency output from the DiTact sensors. As the pressure increases, the frequency increase.

References

1. L. R. Hochberg, D. Bacher, B. Jarosiewicz, N. Y. Masse, J. D. Simeral, J. Vogel, S. Haddadin,

J. Liu, S. S. Cash, P. van der Smagt, J. P. Donoghue, Reach and grasp by people with

tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375 (2012). Medline

doi:10.1038/nature11076

2. J. E. O’Doherty, M. A. Lebedev, P. J. Ifft, K. Z. Zhuang, S. Shokur, H. Bleuler, M. A.

Nicolelis, Active tactile exploration using a brain-machine-brain interface. Nature 479,

228–231 (2011). Medline doi:10.1038/nature10489

3. A. Abbott, Neuroprosthetics: In search of the sixth sense. Nature 442, 125–127 (2006).

Medline doi:10.1038/442125a

4. S. Raspopovic, M. Capogrosso, F. M. Petrini, M. Bonizzato, J. Rigosa, G. Di Pino, J.

Carpaneto, M. Controzzi, T. Boretius, E. Fernandez, G. Granata, C. M. Oddo, L. Citi, A.

L. Ciancio, C. Cipriani, M. C. Carrozza, W. Jensen, E. Guglielmelli, T. Stieglitz, P. M.

Rossini, S. Micera, Restoring natural sensory feedback in real-time bidirectional hand

prostheses. Sci. Transl. Med. 6, 222ra19 (2014). Medline

doi:10.1126/scitranslmed.3006820

5. M. Lotze, W. Grodd, N. Birbaumer, M. Erb, E. Huse, H. Flor, Does use of a myoelectric

prosthesis prevent cortical reorganization and phantom limb pain? Nat. Neurosci. 2, 501–

502 (1999). Medline doi:10.1038/9145

6. D. W. Tan, M. A. Schiefer, M. W. Keith, J. R. Anderson, J. Tyler, D. J. Tyler, A neural

interface provides long-term stable natural touch perception. Sci. Transl. Med. 6,

257ra138 (2014). Medline doi:10.1126/scitranslmed.3008669

7. S. C. B. Mannsfeld, B. C. Tee, R. M. Stoltenberg, C. V. Chen, S. Barman, B. V. Muir, A. N.

Sokolov, C. Reese, Z. Bao, Highly sensitive flexible pressure sensors with

microstructured rubber dielectric layers. Nat. Mater. 9, 859–864 (2010). Medline

doi:10.1038/nmat2834

8. G. Schwartz, B. C. Tee, J. Mei, A. L. Appleton, H. Kim, H. Wang, Z. Bao, Flexible polymer

transistors with high pressure sensitivity for application in electronic skin and health

monitoring. Nat. Commun. 4, 1859 (2013). Medline doi:10.1038/ncomms2832

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22596161&dopt=Abstracthttp://dx.doi.org/10.1038/nature11076http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=21976021&dopt=Abstracthttp://dx.doi.org/10.1038/nature10489http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16837993&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16837993&dopt=Abstracthttp://dx.doi.org/10.1038/442125ahttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24500407&dopt=Abstracthttp://dx.doi.org/10.1126/scitranslmed.3006820http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10448212&dopt=Abstracthttp://dx.doi.org/10.1038/9145http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25298320&dopt=Abstracthttp://dx.doi.org/10.1126/scitranslmed.3008669http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20835231&dopt=Abstracthttp://dx.doi.org/10.1038/nmat2834http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23673644&dopt=Abstracthttp://dx.doi.org/10.1038/ncomms2832

9. M. Kaltenbrunner, T. Sekitani, J. Reeder, T. Yokota, K. Kuribara, T. Tokuhara, M. Drack, R.

Schwödiauer, I. Graz, S. Bauer-Gogonea, S. Bauer, T. Someya, An ultra-lightweight

design for imperceptible plastic electronics. Nature 499, 458–463 (2013). Medline

doi:10.1038/nature12314

10. T. Sekitani, T. Yokota, U. Zschieschang, H. Klauk, S. Bauer, K. Takeuchi, M. Takamiya, T.

Sakurai, T. Someya, Organic nonvolatile memory transistors for flexible sensor arrays.

Science 326, 1516–1519 (2009). Medline

11. D.-H. Kim, N. Lu, R. Ma, Y. S. Kim, R. H. Kim, S. Wang, J. Wu, S. M. Won, H. Tao, A.

Islam, K. J. Yu, T. I. Kim, R. Chowdhury, M. Ying, L. Xu, M. Li, H. J. Chung, H. Keum,

M. McCormick, P. Liu, Y. W. Zhang, F. G. Omenetto, Y. Huang, T. Coleman, J. A.

Rogers, Epidermal electronics. Science 333, 838–843 (2011). Medline

doi:10.1126/science.1206157

12. J. Kim, M. Lee, H. J. Shim, R. Ghaffari, H. R. Cho, D. Son, Y. H. Jung, M. Soh, C. Choi, S.

Jung, K. Chu, D. Jeon, S. T. Lee, J. H. Kim, S. H. Choi, T. Hyeon, D. H. Kim,

Stretchable silicon nanoribbon electronics for skin prosthesis. Nat. Commun. 5, 5747

(2014). Medline doi:10.1038/ncomms6747

13. K. Takei, T. Takahashi, J. C. Ho, H. Ko, A. G. Gillies, P. W. Leu, R. S. Fearing, A. Javey,

Nanowire active-matrix circuitry for low-voltage macroscale artificial skin. Nat. Mater.

9, 821–826 (2010). Medline doi:10.1038/nmat2835

14. E. P. Gardner, Touch (eLS/Wiley Online Library, 2001). doi:10.1038/npg.els.0000219

15. T. N. Ng, D. E. Schwartz, L. L. Lavery, G. L. Whiting, B. Russo, B. Krusor, J. Veres, P.

Bröms, L. Herlogsson, N. Alam, O. Hagel, J. Nilsson, C. Karlsson, Scalable printed

electronics: An organic decoder addressing ferroelectric non-volatile memory. Sci. Rep.

2, 585 (2012). doi:10.1038/srep00585

16. P. Mei, T. N. Ng, R. A. Lujan, D. E. Schwartz, S. Kor, B. S. Krusor, J. Veres, Utilizing high

resolution and reconfigurable patterns in combination with inkjet printing to produce high

performance circuits. Appl. Phys. Lett. 105, 123301 (2014). doi:10.1063/1.4896547

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=23887430&dopt=Abstracthttp://dx.doi.org/10.1038/nature12314http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20007895&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=21836009&dopt=Abstracthttp://dx.doi.org/10.1126/science.1206157http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25490072&dopt=Abstracthttp://dx.doi.org/10.1038/ncomms6747http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20835235&dopt=Abstracthttp://dx.doi.org/10.1038/nmat2835http://dx.doi.org/10.1063/1.4896547

17. T. Sekitani, U. Zschieschang, H. Klauk, T. Someya, Flexible organic transistors and circuits

with extreme bending stability. Nat. Mater. 9, 1015–1022 (2010). Medline

doi:10.1038/nmat2896

18. M. Knibestöl, Stimulus-response functions of slowly adapting mechanoreceptors in the

human glabrous skin area. J. Physiol. 245, 63–80 (1975). Medline

doi:10.1113/jphysiol.1975.sp010835

19. D. A. Nowak, J. Hermsdörfer, Grip force behavior during object manipulation in

neurological disorders: Toward an objective evaluation of manual performance deficits.

Mov. Disord. 20, 11–25 (2005). Medline doi:10.1002/mds.20299

20. B. C. K. Tee, A. Chortos, R. R. Dunn, G. Schwartz, E. Eason, Z. Bao, Tunable flexible

pressure sensors using microstructured elastomer geometries for intuitive electronics.

Adv. Funct. Mater. 24, 5427–5434 (2014). doi:10.1002/adfm.201400712

21. A. Canales, X. Jia, U. P. Froriep, R. A. Koppes, C. M. Tringides, J. Selvidge, C. Lu, C. Hou,

L. Wei, Y. Fink, P. Anikeeva, Multifunctional fibers for simultaneous optical, electrical

and chemical interrogation of neural circuits in vivo. Nat. Biotechnol. 33, 277–284

(2015). Medline doi:10.1038/nbt.3093

22. I. R. Minev, P. Musienko, A. Hirsch, Q. Barraud, N. Wenger, E. M. Moraud, J. Gandar, M.

Capogrosso, T. Milekovic, L. Asboth, R. F. Torres, N. Vachicouras, Q. Liu, N. Pavlova,

S. Duis, A. Larmagnac, J. Vörös, S. Micera, Z. Suo, G. Courtine, S. P. Lacour, Electronic

dura mater for long-term multimodal neural interfaces. Science 347, 159–163 (2015).

Medline doi:10.1126/science.1260318

23. L. A. Gunaydin, O. Yizhar, A. Berndt, V. S. Sohal, K. Deisseroth, P. Hegemann, Ultrafast

optogenetic control. Nat. Neurosci. 13, 387–392 (2010). Medline doi:10.1038/nn.2495

24. J. Mattis, K. M. Tye, E. A. Ferenczi, C. Ramakrishnan, D. J. O’Shea, R. Prakash, L. A.

Gunaydin, M. Hyun, L. E. Fenno, V. Gradinaru, O. Yizhar, K. Deisseroth, Principles for

applying optogenetic tools derived from direct comparative analysis of microbial opsins.

Nat. Methods 9, 159–172 (2012). Medline doi:10.1038/nmeth.1808

25. H. E. Kato, F. Zhang, O. Yizhar, C. Ramakrishnan, T. Nishizawa, K. Hirata, J. Ito, Y. Aita,

T. Tsukazaki, S. Hayashi, P. Hegemann, A. D. Maturana, R. Ishitani, K. Deisseroth, O.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=21057499&dopt=Abstracthttp://dx.doi.org/10.1038/nmat2896http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1127614&dopt=Abstracthttp://dx.doi.org/10.1113/jphysiol.1975.sp010835http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15455447&dopt=Abstracthttp://dx.doi.org/10.1002/mds.20299http://dx.doi.org/10.1002/adfm.201400712http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25599177&dopt=Abstracthttp://dx.doi.org/10.1038/nbt.3093http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25574019&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25574019&dopt=Abstracthttp://dx.doi.org/10.1126/science.1260318http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20081849&dopt=Abstracthttp://dx.doi.org/10.1038/nn.2495http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22179551&dopt=Abstracthttp://dx.doi.org/10.1038/nmeth.1808

Nureki, Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482,

369–374 (2012). Medline

26. H. Haeberle, E. A. Lumpkin, Merkel cells in somatosensation. Chemosens. Percept. 1, 110–

118 (2008). Medline doi:10.1007/s12078-008-9012-6

27. A. Berndt, S. Y. Lee, C. Ramakrishnan, K. Deisseroth, Structure-guided transformation of

channelrhodopsin into a light-activated chloride channel. Science 344, 420–424 (2014).

Medline doi:10.1126/science.1252367

28. J.-M. Bonard, H. Kind, T. Stöckli, L.-O. Nilsson, Field emission from carbon nanotubes: The

first five years. Solid State Electron. 45, 893–914 (2001). doi:10.1016/S0038-

1101(00)00213-6

29. M. A. McCarthy, B. Liu, A. G. Rinzler, High current, low voltage carbon nanotube enabled

vertical organic field effect transistors. Nano Lett. 10, 3467–3472 (2010). Medline

doi:10.1021/nl101589x

30. D. Bloor, K. Donnelly, P. J. Hands, P. Laughlin, D. Lussey, A metal-polymer composite with

unusual properties. J. Phys. D 38, 2851–2860 (2005). doi:10.1088/0022-3727/38/16/018

31. J. Y. Lin, M. Z. Lin, P. Steinbach, R. Y. Tsien, Characterization of engineered

channelrhodopsin variants with improved properties and kinetics. Biophys. J. 96, 1803–

1814 (2009). Medline doi:10.1016/j.bpj.2008.11.034

32. J. P. Vedel, J. P. Roll, Response to pressure and vibration of slowly adapting cutaneous

mechanoreceptors in the human foot. Neurosci. Lett. 34, 289–294 (1982). Medline

doi:10.1016/0304-3940(82)90190-2

33. P. R. Burgess, J. Mei, R. P. Tuckett, K. W. Horch, C. M. Ballinger, D. A. Poulos, The neural

signal for skin indentation depth. I. Changing indentations. J. Neurosci. 3, 1572–1585

(1983). Medline

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22266941&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19834574&dopt=Abstracthttp://dx.doi.org/10.1007/s12078-008-9012-6http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24763591&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=24763591&dopt=Abstracthttp://dx.doi.org/10.1126/science.1252367http://dx.doi.org/10.1016/S0038-1101(00)00213-6http://dx.doi.org/10.1016/S0038-1101(00)00213-6http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20707327&dopt=Abstracthttp://dx.doi.org/10.1021/nl101589xhttp://dx.doi.org/10.1088/0022-3727/38/16/018http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19254539&dopt=Abstracthttp://dx.doi.org/10.1016/j.bpj.2008.11.034http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6298676&dopt=Abstracthttp://dx.doi.org/10.1016/0304-3940(82)90190-2http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6875657&dopt=Abstract

SOM.page.1.EXPRESS.no.movies.pdfA skin-inspired organic digital mechanoreceptor

aaa9306TeeRefs.pdfReferences