## Printed biophotonic sensors for blood and tissue oximetry

Organic optoelectronic probe for transmission-mode pulse oximetry.


Reflection-mode pulse oximetry using an organic oximeter probe on a volunteer's wrist.


Oximetry, the technique for determining oxygen saturation, optically measures the light absorption of oxygenated and deoxygenated blood and tissue at two different wavelengths. In 2014, we demonstrated the first all-organic optoelectronic oximeter sensor composed of organic light-emitting diodes (OLEDs) and an organic photodiode (OPD) to accurately measure pulse rate and oxygenation with errors of 1% and 2%, respectively [1]. This transmission-mode probe demonstrated that oximetry can be performed with organic optoelectronics. However, to realize the true potential of organic optoelectronics for oximetry, a reflection-mode operation is essential that allows sensor placement on different parts of the body. After optimizing the sensor design and the printing process, in 2017, we reported a reflection-mode organic oximeter probe and performed blood oxygenation measurements on the wrist [2].

Relevant publications:

1. All-organic optoelectronic sensor for pulse oximetry Nature communications, 2014 5, *Equal contribution. Media coverage: UC Berkeley Grad News, NSF Science 360 News, UC Berkeley News Center, Phys.Org, ScienceDaily, MSN News, Yahoo News, and many more.

Pulse oximetry is a ubiquitous non-invasive medical sensing method for measuring pulse rate and arterial blood oxygenation. Conventional pulse oximeters use expensive optoelectronic components that restrict sensing locations to finger tips or ear lobes due to their rigid form and area-scaling complexity. In this work, we report a pulse oximeter sensor based on organic materials, which are compatible with flexible substrates. Green (532 nm) and red (626 nm) organic light-emitting diodes (OLEDs) are used with an organic photodiode (OPD) sensitive at the aforementioned wavelengths. The sensor’s active layers are deposited from solution-processed materials via spin-coating and printing techniques. The all-organic optoelectronic oximeter sensor is interfaced with conventional electronics at 1 kHz and the acquired pulse rate and oxygenation are calibrated and compared with a commercially available oximeter. The organic sensor accurately measures pulse rate and oxygenation with errors of 1% and 2%, respectively.

1. Flexible blade-coated multicolor polymer light-emitting diodes for optoelectronic sensors Advanced Materials, 2017 29, 22.

A method to print two materials of different functionality during the same printing step is presented. In printed electronics, devices are built layer by layer and conventionally only one type of material is deposited in one pass. Here, the challenges involving printing of two emissive materials to form polymer light-emitting diodes (PLEDs) that emit light of different wavelengths without any significant changes in the device characteristics are described. The surface-energy-patterning technique is utilized to print materials in regions of interest. This technique proves beneficial in reducing the amount of ink used during blade coating and improving the reproducibility of printed films. A variety of colors (green, red, and near-infrared) are demonstrated and characterized. This is the first known attempt to print multiple materials by blade coating. These devices are further used in conjunction with a commercially available photodiode to perform blood oxygenation measurements on the wrist, where common accessories are worn. Prior to actual application, the threshold conditions for each color are discussed, in order to acquire a stable and reproducible photoplethysmogram (PPG) signal. Finally, based on the conditions, retrieved PPG and oxygenation measurements are successfully performed on the wrist with green and red PLEDs.

@article{han2017flexible, title = {Flexible blade-coated multicolor polymer light-emitting diodes for optoelectronic sensors}, author = {Han, Donggeon and Khan, Yasser and Ting, Jonathan and King, Simon M and Yaacobi-Gross, Nir and Humphries, Martin J and Newsome, Christopher J and Arias, Ana C}, journal = {Advanced Materials}, volume = {29}, number = {22}, pages = {1606206}, year = {2017}, publisher = {Wiley Online Library}, url = {http://dx.doi.org/10.1002/adma.201606206}, doi = {10.1002/adma.201606206}, thumbnail = {han2017flexible.png}, pdf = {han2017flexible.pdf} }

## Printed bioelectronic sensors for BIA (Bioimpedance Analysis), ECG (Electrocardiography), and EMG (Electromyography)

Inkjet-printed flexible gold electrode array consisting of 31 electrodes, which is used for impedance mapping of conformal surfaces.


Non-invasively mapping pressure-induced tissue damage with inkjet-printed flexible gold electrode array.


Bioelectronic interfaces require electrodes that are mechanically flexible and chemically inert. Flexibility allows pristine electrode contact to skin and tissue, and chemical inertness prevents electrodes from reacting with biological fluids and living tissues. Since a manufacturing process to fabricate gold electrode arrays on plastic substrates is elusive, we devised a fabrication and low-temperature sintering ($\approx 200 ^\circ C$) technique to print gold electrodes. Utilizing the versatility of printing and plastic electronic processes, electrode arrays were fabricated and used for impedance mapping of conformal surfaces at 15 kHz [3].

A more direct application of the array was to non-invasively map pressure-induced tissue damage. Here, the array was used to detect pressure ulcers in an animal model, even before the damages were observed visually. Our results demonstrated the feasibility of an automated, non-invasive “smart bandage” for early detection of pressure ulcers [4]. Moreover, for a different project, we used the gold electrodes printed on a wearable sensor patch as electrocardiography (ECG) electrodes.

Relevant publications:

1. Inkjet-printed flexible gold electrode arrays for bioelectronic interfaces Advanced Functional Materials, 2016 26, 7. Cover article.

Bioelectronic interfaces require electrodes that are mechanically flexible and chemically inert. Flexibility allows pristine electrode contact to skin and tissue, and chemical inertness prevents electrodes from reacting with biological fluids and living tissues. Therefore, flexible gold electrodes are ideal for bioimpedance and biopotential measurements such as bioimpedance tomography, electrocardiography (ECG), electroencephalography (EEG), and electromyography (EMG). However, a manufacturing process to fabricate gold electrode arrays on plastic substrates is still elusive. In this work, a fabrication and low-temperature sintering (≈200 °C) technique is demonstrated to fabricate gold electrodes. At low-temperature sintering conditions, lines of different widths demonstrate different sintering speeds. Therefore, the sintering condition is targeted toward the widest feature in the design layout. Manufactured electrodes show minimum feature size of 62 μm and conductivity values of 5 × 10 6 S m−1. Utilizing the versatility of printing and plastic electronic processes, electrode arrays consisting of 31 electrodes with electrode-to-electrode spacing ranging from 2 to 7 mm are fabricated and used for impedance mapping of conformal surfaces at 15 kHz. Overall, the fabrication process of an inkjet-printed gold electrode array that is electrically reproducible, mechanically robust, and promising for bioimpedance and biopotential measurements is demonstrated.

@article{khan2016inkjet, title = {Inkjet-printed flexible gold electrode arrays for bioelectronic interfaces}, author = {Khan*, Yasser and Pavinatto*, Felippe J and Lin, Monica C and Liao, Amy and Swisher, Sarah L and Mann, Kaylee and Subramanian, Vivek and Maharbiz, Michel M and Arias, Ana C}, journal = {Advanced Functional Materials}, volume = {26}, number = {7}, pages = {1004--1013}, year = {2016}, publisher = {Wiley Online Library}, url = {http://dx.doi.org/10.1002/adfm.201503316}, doi = {10.1002/adfm.201503316}, thumbnail = {khan2016inkjet.png}, pdf = {khan2016inkjet.pdf}, note = {Cover article.} }

1. Impedance sensing device enables early detection of pressure ulcers in vivo Nature communications, 2015 6,

When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Currently, no method exists to detect early tissue damage and enable intervention. Here we demonstrate a flexible, electronic device that non-invasively maps pressure-induced tissue damage, even when such damage cannot be visually observed. Using impedance spectroscopy across flexible electrode arrays in vivo on a rat model, we find that impedance is robustly correlated with tissue health across multiple animals and wound types. Our results demonstrate the feasibility of an automated, non-invasive ‘smart bandage’ for early detection of pressure ulcers.

@article{swisher2015impedance, title = {Impedance sensing device enables early detection of pressure ulcers in vivo}, author = {Swisher, Sarah L and Lin, Monica C and Liao, Amy and Leeflang, Elisabeth J and Khan, Yasser and Pavinatto, Felippe J and Mann, Kaylee and Naujokas, Agne and Young, David and Roy, Shuvo and Harrison, Michael R and Arias, Ana C and Subramanian, Vivek and Maharbiz, Michel M}, journal = {Nature communications}, volume = {6}, pages = {6575}, year = {2015}, publisher = {Nature Publishing Group}, url = {http://dx.doi.org/10.1038/ncomms7575}, doi = {10.1038/ncomms7575}, thumbnail = {swisher2015impedance.png}, pdf = {swisher2015impedance.pdf}, note = {Media coverage: }, media_1 = {BBC News, }, media_1_link = {http://www.bbc.com/news/health-31903367}, media_2 = {UC Berkeley News Center, }, media_2_link = {http://newscenter.berkeley.edu/2015/03/17/smart-bandages-detect-bedsores/}, media_3 = {Futurity, }, media_3_link = {http://www.futurity.org/smart-bandage-bedsores-876942/}, media_4 = {NSF News, }, media_4_link = {https://www.nsf.gov/news/news_summ.jsp?cntn_id=134610}, media_5 = {ACM Communications, }, media_5_link = {https://cacm.acm.org/news/184717-smart-bandage-detects-bedsores-before-they-are-visible-to-doctors/fulltext}, media_6 = {and many more.}, media_6_link = {https://www.altmetric.com/details/3798805} }

## Wearable Medical Devices

Overview of a wearable sensor platform, where flexible sensors are utilized for real-time health monitoring.


A skin-like flexible and wearable sensor patch, seamlessly measuring body’s vital signs - realizing this device is a major goal of my doctoral work. My research focuses mainly on the system-level implementation of wearable medical devices, with an emphasis on flexible and printed bioelectronic and biophotonic sensors.

Wearable and flexible sensors are promising for medical sensing because they provide an improved signal-to-noise ratio (SNR) by establishing a conformal skin-sensor interface [5]. Moreover, in my work, printing techniques are used to fabricate the sensors, which ensures large-area scaling of the devices. Additionally with the rapid prototyping capability of printing, the sensors can be designed in different sizes and shapes, accommodating the needs of a diverse population.

An overview and system design of the wearable sensor patch (WSP) enabled by flexible hybrid electronics. The sensor side faces down toward the skin, and the component side faces up. The printed gold ECG electrodes and the thermistor are shown.


A flexible power source integrating a lithium-ion battery and amorphous silicon solar module for powering wearable health monitoring devices.


Flexible hybrid electronics (FHE) are a fundamental enabling technology for system-level implementation of novel printed and flexible devices. FHE bring together soft and hard electronics into a single platform, where the soft devices are used for conformal sensor interfaces, and the hard silicon-based devices provide the computational backbone and compatibility with existing electronic systems and standards. The interfacing of soft and hard electronics is a key challenge for flexible hybrid electronics.

For a project in collaboration with Binghamton University, i3 Electronics, Lockheed Martin, and American Semiconductor, we demonstrated a single substrate interfacing approach, where soft devices, i.e., sensors, are directly printed on Kapton polyimide substrates that are widely used for fabricating flexible printed circuit boards (FPCBs). Utilizing a process flow compatible with the FPCB assembly process, a wearable sensor patch was fabricated composed of inkjet-printed gold ECG electrodes and a stencil-printed nickel oxide thermistor [6]. In another project, for powering wearable health monitoring devices, we demonstrated a flexible power source by integrating a lithium-ion battery and amorphous silicon solar module [7].

Relevant publications:

1. Monitoring of vital signs with flexible and wearable medical devices Advanced Materials, 2016 28, 22.

Advances in wireless technologies, low-power electronics, the internet of things, and in the domain of connected health are driving innovations in wearable medical devices at a tremendous pace. Wearable sensor systems composed of flexible and stretchable materials have the potential to better interface to the human skin, whereas silicon-based electronics are extremely efficient in sensor data processing and transmission. Therefore, flexible and stretchable sensors combined with low-power silicon-based electronics are a viable and efficient approach for medical monitoring. Flexible medical devices designed for monitoring human vital signs, such as body temperature, heart rate, respiration rate, blood pressure, pulse oxygenation, and blood glucose have applications in both fitness monitoring and medical diagnostics. As a review of the latest development in flexible and wearable human vitals sensors, the essential components required for vitals sensors are outlined and discussed here, including the reported sensor systems, sensing mechanisms, sensor fabrication, power, and data processing requirements.

@article{khan2016monitoring, title = {Monitoring of vital signs with flexible and wearable medical devices}, author = {Khan, Yasser and Ostfeld, Aminy E and Lochner, Claire M and Pierre, Adrien and Arias, Ana C}, journal = {Advanced Materials}, volume = {28}, number = {22}, pages = {4373--4395}, year = {2016}, publisher = {Wiley Online Library}, url = {http://dx.doi.org/10.1002/adma.201504366}, doi = {10.1002/adma.201504366}, thumbnail = {khan2016monitoring.png}, pdf = {khan2016monitoring.pdf} }

1. Flexible hybrid electronics: Direct interfacing of soft and hard electronics for wearable health monitoring Advanced Functional Materials, 2016 26, 47.

The interfacing of soft and hard electronics is a key challenge for flexible hybrid electronics. Currently, a multisubstrate approach is employed, where soft and hard devices are fabricated or assembled on separate substrates, and bonded or interfaced using connectors; this hinders the flexibility of the device and is prone to interconnect issues. Here, a single substrate interfacing approach is reported, where soft devices, i.e., sensors, are directly printed on Kapton polyimide substrates that are widely used for fabricating flexible printed circuit boards (FPCBs). Utilizing a process flow compatible with the FPCB assembly process, a wearable sensor patch is fabricated composed of inkjet-printed gold electrocardiography (ECG) electrodes and a stencil-printed nickel oxide thermistor. The ECG electrodes provide 1 mVp–p ECG signal at 4.7 cm electrode spacing and the thermistor is highly sensitive at normal body temperatures, and demonstrates temperature coefficient, α ≈ –5.84% K–1 and material constant, β ≈ 4330 K. This sensor platform can be extended to a more sophisticated multisensor platform where sensors fabricated using solution processable functional inks can be interfaced to hard electronics for health and performance monitoring, as well as internet of things applications.

@article{khan2016flexible, title = {Flexible hybrid electronics: Direct interfacing of soft and hard electronics for wearable health monitoring}, author = {Khan, Yasser and Garg, Mohit and Gui, Qiong and Schadt, Mark and Gaikwad, Abhinav and Han, Donggeon and Yamamoto, Natasha AD and Hart, Paul and Welte, Robert and Wilson, William and Czarnecki, Steve and Poliks, Mark and Jin, Zhanpeng and Ghose, Kanad and Egitto, Frank and Turner, James and Arias, Ana C}, journal = {Advanced Functional Materials}, volume = {26}, number = {47}, pages = {8764--8775}, year = {2016}, publisher = {Wiley Online Library}, url = {http://dx.doi.org/10.1002/adfm.201603763}, doi = {10.1002/adfm.201603763}, thumbnail = {khan2016flexible.png}, pdf = {khan2016flexible.pdf} }

1. High-performance flexible energy storage and harvesting system for wearable electronics Scientific reports, 2016 6,

This paper reports on the design and operation of a flexible power source integrating a lithium ion battery and amorphous silicon solar module, optimized to supply power to a wearable health monitoring device. The battery consists of printed anode and cathode layers based on graphite and lithium cobalt oxide, respectively, on thin flexible current collectors. It displays energy density of 6.98 mWh/cm2 and demonstrates capacity retention of 90% at 3C discharge rate and  99% under 100 charge/discharge cycles and 600 cycles of mechanical flexing. A solar module with appropriate voltage and dimensions is used to charge the battery under both full sun and indoor illumination conditions, and the addition of the solar module is shown to extend the battery lifetime between charging cycles while powering a load. Furthermore, we show that by selecting the appropriate load duty cycle, the average load current can be matched to the solar module current and the battery can be maintained at a constant state of charge. Finally, the battery is used to power a pulse oximeter, demonstrating its effectiveness as a power source for wearable medical devices.

@article{ostfeld2016high, title = {High-performance flexible energy storage and harvesting system for wearable electronics}, author = {Ostfeld, Aminy E and Gaikwad, Abhinav M and Khan, Yasser and Arias, Ana C}, journal = {Scientific reports}, volume = {6}, pages = {26122}, year = {2016}, publisher = {Nature Publishing Group}, url = {http://dx.doi.org/10.1038/srep26122}, doi = {10.1038/srep26122}, thumbnail = {ostfeld2016high.png}, pdf = {ostfeld2016high.pdf} }

## Printed Sensors

Relevant publications: