Michelle Khine - Academia.edu (original) (raw)

Papers by Michelle Khine

Over 5.8 million people in the U.S. and 23 million people worldwide live with congestive heart fa... more Over 5.8 million people in the U.S. and 23 million people worldwide live with congestive heart failure (CHF) wherein the heart cannot adequately maintain blood circulation [1, 2]. More than half of those who develop CHF die within 5 years of diagnosis [3]. Complications of CHF is the leading cause of hospitalizations in the U.S. [4]. In 2015, CHF was responsible for $24 billion in healthcare costs and is projected to double in the next 15 years [3]. CHF is now the only cardiac disease increasing in prevalence in the U.S. [1].

Complex quasi-periodic nano- and micro- structures are finding increased importance in diverse fi... more Complex quasi-periodic nano- and micro- structures are finding increased importance in diverse fields. Metal wrinkles have potential applications in: molecular detection, optical devices, and high-surface area conductors. We present a simple and ultra-rapid technique to controllably create complex nano- to micro- scale metal wrinkles on the polystyrene (PS) children’s toy Shrinky-Dinks. We are uniquely able to create wrinkles with a large range of wavelengths. The wrinkles also have adjustable periodicity, directionality, aspect ratios, anisotropy and even patterns. Finally, we demonstrate the utility of these patterns, for applications from photonics to cell fate studies.

released the strain to create wavy buckled structures. These wavy buckled structures provided str... more released the strain to create wavy buckled structures. These wavy buckled structures provided strain relief for brittle materials rendering them stretchable. [13,14] Typical wearable strain sensors consist of patterned thin films on flexible elastomeric substrates. Recent developments in creating highly stretchable wearable strain sensors used nanoscale metal thin films, [15] nanoparticles, [16] nanowires (NWs), [17-19] nanotubes, [20-26] and graphene. [27-31] For example, Kang et al. utilized brittle platinum thin films to achieve high sensitivity (GF > 2000), but the strain sensor was only able to withstand strains of up to 2%. [32] Li et al. investigated graphene woven fabric for strain sensing (GF ≈ 1000), but was still limited to a maximum strain of 6%. [33] Conversely, Yan et al. reported highly stretchable graphene-nanocellulose nanopaper that can stretch out to 100% strain, but the strain sensor only had a GF of 7.1. [34] Zaretski et al. reported a highly sensitive strain sensor using metallic nanoislands on graphene with GF 1335 at 1% strain. However, the dynamic range of this sensor was limited, with strain of less than 10% strain. Additionally, the GF dropped to 743 after 19 cycles at 1% strain. [35] Another popular functional material that is used for strain sensing is carbon nanotubes (CNTs). Percolating networks of CNTs on flexible elastomeric substrates have been reported to have electromechanical stability under high strain due to the robust contact between individual CNTs. [36] CNT thin films have also shown the ability to bend repeatedly without fracturing. [37-41] Therefore, percolating networks of CNTs have the potential to be used as highly stretchable strain sensing devices. For instance, Yamada et al. aligned CNT thin film on PDMS and showed 280% strain but low sensitivity (GF < 0.82), [25] and Lipomi et al. investigated spring like structures in the nanotube that reach 150% strain with good conductivity. [22] Ryu et al. showed that aligned CNT fibers grown on flexible substrates were able to stretch out to 900% having GF of up to 47. [42] However, this process required highly ordered alignment of CNT fibers using intricate dry spinning methods. Another aspect to consider for improving wearable strain sensor is the careful selection of the stretchable elastomeric substrate. Many strain sensors have been fabricated using polydimethylsiloxane (PDMS) as the stretchable and flexible substrate due to its flexibility, nontoxicity, ease of fabrication, and biocompatibility. [43,44] Amjadi et al. reported highly flexible, stretchable sensitive strain sensors based on silver nanowires with PDMS that had a GF of 14 at 70% strain. [44] However, many PDMS substrate based strain sensors showed low stretchability with high hysteresis due to poor adhesion between the functional material and substrate polymer, as well as increased friction during the strain. [45,46] Furthermore, PDMS becomes stiffer, delaminates, and slips after absorbing human sweat www.MaterialsViews.com www.advmattechnol.de

Rapid and effective mixing of macromolecular solutions remains a persistent challenge when studyi... more Rapid and effective mixing of macromolecular solutions remains a persistent challenge when studying biochemical reactions. We show here that rapid and enhanced micromixing can be achieved in an easily fabricated (requiring no lithography), topologically simple 3D ...

RSC Advances

A wrinkled gold substrate greatly improves the signaling of electrochemical aptamer-based biosens... more A wrinkled gold substrate greatly improves the signaling of electrochemical aptamer-based biosensors, achieving up to 10-fold increase in signals.

Sensors

The relationship between the robustness of HRV derived by linear and nonlinear methods to the req... more The relationship between the robustness of HRV derived by linear and nonlinear methods to the required minimum data lengths has yet to be well understood. The normal electrocardiography (ECG) data of 14 healthy volunteers were applied to 34 HRV measures using various data lengths, and compared with the most prolonged (2000 R peaks or 750 s) by using the Mann–Whitney U test, to determine the 0.05 level of significance. We found that SDNN, RMSSD, pNN50, normalized LF, the ratio of LF and HF, and SD1 of the Poincaré plot could be adequately computed by small data size (60–100 R peaks). In addition, parameters of RQA did not show any significant differences among 60 and 750 s. However, longer data length (1000 R peaks) is recommended to calculate most other measures. The DFA and Lyapunov exponent might require an even longer data length to show robust results. Conclusions: Our work suggests the optimal minimum data sizes for different HRV measures which can potentially improve the effic...

International Journal of Prognostics and Health Management

Acute injury to aged individuals represents a significant challenge to the global healthcare comm... more Acute injury to aged individuals represents a significant challenge to the global healthcare community as these injuries are frequently treated in a reactive method due to the infeasibility of frequent visits to the hospital for biometric monitoring. However, there is potential to prevent a large number of these cases through passive, at-home monitoring of multiple physiological parameters related to various causes that are common to aged adults in general. This research strives to implement wearable devices, ambient “smart home” devices, and minimally invasive blood and urine analysis to test the feasibility of implementation of a multitude of research-level (i.e. not yet clinically validated) methods simultaneously in a “smart system”. The system comprises measures of balance, breathing, heart rate, metabolic rate, joint flexibility, hydration, and physical performance functions in addition to lab testing related to biological aging and mechanical cell strength. A proof-of-concept...

Analytical Methods

We introduce a simple, scalable, and portable electrochemical aptamer-based system for detection ... more We introduce a simple, scalable, and portable electrochemical aptamer-based system for detection of the SARS-CoV-2 spike protein in saliva with attomolar sensitivity.

Advanced Electronic Materials

Polymers

Soft stretchable sensors rely on polymers that not only withstand large deformations while retain... more Soft stretchable sensors rely on polymers that not only withstand large deformations while retaining functionality but also allow for ease of application to couple with the body to capture subtle physiological signals. They have been applied towards motion detection and healthcare monitoring and can be integrated into multifunctional sensing platforms for enhanced human machine interface. Most advances in sensor development, however, have been aimed towards active materials where nearly all approaches rely on a silicone-based substrate for mechanical stability and stretchability. While silicone use has been advantageous in academic settings, conventional silicones cannot offer self-healing capability and can suffer from manufacturing limitations. This review aims to cover recent advances made in polymer materials for soft stretchable conductors. New developments in substrate materials that are compliant and stretchable but also contain self-healing properties and self-adhesive capab...

Materials

Practical wearable applications of soft strain sensors require sensors capable of not only detect... more Practical wearable applications of soft strain sensors require sensors capable of not only detecting subtle physiological signals, but also of withstanding large scale deformation from body movement. Encapsulation is one technique to protect sensors from both environmental and mechanical stressors. We introduced an encapsulation layer to crack-based wrinkled metallic thin film soft strain sensors as an avenue to improve sensor stretchability, linear response, and robustness. We demonstrate that encapsulated sensors have increased mechanical robustness and stability, displaying a significantly larger linear dynamic range (~50%) and increased stretchability (260% elongation). Furthermore, we discovered that these sensors have post-fracture signal recovery. They maintained conductivity to the 50% strain with stable signal and demonstrated increased sensitivity. We studied the crack formation behind this phenomenon and found encapsulation to lead to higher crack density as the source fo...

Advanced Materials Technologies

npj Digital Medicine

Current methods for continuous respiration monitoring such as respiratory inductive or optoelectr... more Current methods for continuous respiration monitoring such as respiratory inductive or optoelectronic plethysmography are limited to clinical or research settings; most wearable systems reported only measures respiration rate. Here we introduce a wearable sensor capable of simultaneously measuring both respiration rate and volume with high fidelity. Our disposable respiration sensor with a Band-Aid© like formfactor can measure both respiration rate and volume by simply measuring the local strain of the ribcage and abdomen during breathing. We demonstrate that both metrics are highly correlated to measurements from a medical grade continuous spirometer on participants at rest. Additionally, we also show that the system is capable of detecting respiration under various ambulatory conditions. Because these low-powered piezo-resistive sensors can be integrated with wireless Bluetooth units, they can be useful in monitoring patients with chronic respiratory diseases in everyday settings.

Advanced Healthcare Materials

Wrinkled gold thin films on elastomeric substrates are used as robust parallel plate electrodes f... more Wrinkled gold thin films on elastomeric substrates are used as robust parallel plate electrodes for soft capacitive pressure sensors. The wrinkled structures create a robust integration with the polymer, allowing repeated normal force to deform the thin film without failure. By incorporating microridged structures that support the counter electrodes to create air cavities within the elastomeric dielectric layer, pressure sensitivity is further increased to 0.148 kPa-1 over a wide dynamic range of up to 10 kPa. The wide dynamic range and pressure sensitivity of the pressure sensor allow for consistent measurements of the pressure exerted by the radial artery located on the wrist. The soft capacitive pressure sensor displays comparable results when tested against an FDA approved device (Clearsight, Edwards Lifesciences, Irvine, CA) measuring beat-to-beat blood pressure. These soft pressure sensors using wrinkled thin films, therefore, illustrate considerable potential to continuously monitor beat-to-beat blood pressure.

Macromolecular Materials and Engineering

Advanced Materials Technologies

Piezoelectric materials are materials that can produce electrical charges when induced with mecha... more Piezoelectric materials are materials that can produce electrical charges when induced with mechanical stress and have been widely used in pressure sensors. [30] For example, Chen et al. reported vertically aligned piezoelectric P(VDF-TrFE) nanowires that were able to detect blood pulse on the wrist. [12] The device was able to output a maximum of 4.8 V with a current density of 0.11 µA cm −2. These sensors had high response times and limits of detection of less than 2 Pa, but could only provide dynamic information which greatly limits its applications. Capacitive pressure sensors consist of a compliant dielectric layer sandwiched by two parallel conductive electrodes. When a pressure is applied, the dielectric layer gets compressed generating an increase in capacitance. Capacitive pressure sensors have been characterized with high signal linearity, but have low pressure sensitivities. Zhao et al. reported a flexible capacitive array pressure sensor with a pressure sensitivity of 1.45 MPa −1. [4] Yao and Zhu have demonstrated that silver nanowires can also be used to fabricate stretchable conductors allowing for pressure sensitivities of up to 1.62 MPa −1. [31] Zang et al. have also demonstrated that compressible dielectric layers can also be incorporated into organic thin-film transistors (OTFTs) achieving pressure sensitivities of up to 192 kPa −1. [32] While high sensitivities were achieved, the device required high voltages to achieve high sensitivities (V ds = −60 V). Although capacitive pressure sensors exhibit highly linear signal responses, they are generally characterized with poor sensitivity due to the small compression of the dielectric layer. Higher sensitivities can only be achieved by using higher voltage sources. Piezoresistive sensors work by detecting the change in resistance upon actuation. This is typically structured by coupling two conductive rough surfaces together. By doing so, the number of electrical contacts can be changed by the amount of mechanical pressure that is applied, effectively increasing or lowering resistivity between the electrodes. For example, Park et al. fabricated polydimethylsiloxane (PDMS)/carbon nanotube (CNT) composite interlocking microdome surfaces achieving pressure sensitivities of up to 15.1 kPa −1. [33] Rough surfaces could also be made by molding silk textile with CNT/ PDMS composite materials to achieve pressure sensitivities of up to 1.80 kPa −1. [34] Silver nanowire networks have also been Highly sensitive and flexible components are essential for applications in wearable electronics. Using low-cost and rapid prototyping methods, piezoresistive pressure sensors are fabricated using shrink-film, a shape memory polymer that retracts upon heat, to introduce wrinkling in carbon nanotube thin films, which improves both elasticity and pressure sensitivity. The wrinkles not only provide strain relief, but it also improves pressure sensitivity by 12 800 fold with a response time of less than 20 ms. The improved sensitivity is due to the surface roughness of the wrinkles. When two wrinkled electrodes are coupled together, the number of electrical contact points changes upon actuation thereby changing the electrical resistivity. This study then demonstrates wearable applications, such as pulsatile blood flow monitoring and voice detection using these sensitive pressure sensors.

Methods (San Diego, Calif.), Jan 16, 2017

Neural stem cell (NSC) cultures have been considered technically challenging for time-lapse analy... more Neural stem cell (NSC) cultures have been considered technically challenging for time-lapse analysis due to high motility, photosensitivity, and growth at confluent densities. We have tested feasibility of long-term live-cell time-lapse analysis for NSC migration and differentiation studies. Here, we describe a method to study the dynamics of cell cycle, migration, and lineage selection in cultured multipotent mouse or human NSCs using single-cell tracking during a long-term, 7-14 day live-cell time-lapse analysis. We used in-house made PDMS inserts with five microwells on a glass coverslip petri-dish to constrain NSC into the area of acquisition during long-term live-cell imaging. In parallel, we have defined image acquisition settings for single-cell tracking of cell cycle dynamics using Fucci-reporter mouse NSC for 7 days as well as lineage selection and migration using human NSC for 14 days. Overall, we show that adjustments of live-cell analysis settings can extend the time per...

Stem cell reports, Nov 14, 2017

Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a d... more Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge. Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses. As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets. Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space. Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS) electrically paced at a range of frequencies and exposed to a library of compounds. A generated metric is effective for th...

Biofabrication

The vascularization of tissue grafts is critical for maintaining viability of the cells within a ... more The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues.

Optical Materials Express

We demonstrate increased intra-ensemble energy transfer (ET) in monodispersed semiconducting quan... more We demonstrate increased intra-ensemble energy transfer (ET) in monodispersed semiconducting quantum dots (QDs), mediated by localized plasmons on metallic thin films with nano-scale wrinkles. The increased ET results in a net spectral red-shift, up to threefold increase in emission intensity, and a faster radiative recombination rate of the ensemble. The extent of the red-shift is dependent on QD size, and is largest for the QDs where the absorption spectrum overlaps the plasmonic resonance of the film. This effect has a uniform, macroscopic manifestation and may provide an inexpensive option of improving performance of QD based photovoltaic devices.

Over 5.8 million people in the U.S. and 23 million people worldwide live with congestive heart fa... more Over 5.8 million people in the U.S. and 23 million people worldwide live with congestive heart failure (CHF) wherein the heart cannot adequately maintain blood circulation [1, 2]. More than half of those who develop CHF die within 5 years of diagnosis [3]. Complications of CHF is the leading cause of hospitalizations in the U.S. [4]. In 2015, CHF was responsible for $24 billion in healthcare costs and is projected to double in the next 15 years [3]. CHF is now the only cardiac disease increasing in prevalence in the U.S. [1].

Complex quasi-periodic nano- and micro- structures are finding increased importance in diverse fi... more Complex quasi-periodic nano- and micro- structures are finding increased importance in diverse fields. Metal wrinkles have potential applications in: molecular detection, optical devices, and high-surface area conductors. We present a simple and ultra-rapid technique to controllably create complex nano- to micro- scale metal wrinkles on the polystyrene (PS) children’s toy Shrinky-Dinks. We are uniquely able to create wrinkles with a large range of wavelengths. The wrinkles also have adjustable periodicity, directionality, aspect ratios, anisotropy and even patterns. Finally, we demonstrate the utility of these patterns, for applications from photonics to cell fate studies.

released the strain to create wavy buckled structures. These wavy buckled structures provided str... more released the strain to create wavy buckled structures. These wavy buckled structures provided strain relief for brittle materials rendering them stretchable. [13,14] Typical wearable strain sensors consist of patterned thin films on flexible elastomeric substrates. Recent developments in creating highly stretchable wearable strain sensors used nanoscale metal thin films, [15] nanoparticles, [16] nanowires (NWs), [17-19] nanotubes, [20-26] and graphene. [27-31] For example, Kang et al. utilized brittle platinum thin films to achieve high sensitivity (GF > 2000), but the strain sensor was only able to withstand strains of up to 2%. [32] Li et al. investigated graphene woven fabric for strain sensing (GF ≈ 1000), but was still limited to a maximum strain of 6%. [33] Conversely, Yan et al. reported highly stretchable graphene-nanocellulose nanopaper that can stretch out to 100% strain, but the strain sensor only had a GF of 7.1. [34] Zaretski et al. reported a highly sensitive strain sensor using metallic nanoislands on graphene with GF 1335 at 1% strain. However, the dynamic range of this sensor was limited, with strain of less than 10% strain. Additionally, the GF dropped to 743 after 19 cycles at 1% strain. [35] Another popular functional material that is used for strain sensing is carbon nanotubes (CNTs). Percolating networks of CNTs on flexible elastomeric substrates have been reported to have electromechanical stability under high strain due to the robust contact between individual CNTs. [36] CNT thin films have also shown the ability to bend repeatedly without fracturing. [37-41] Therefore, percolating networks of CNTs have the potential to be used as highly stretchable strain sensing devices. For instance, Yamada et al. aligned CNT thin film on PDMS and showed 280% strain but low sensitivity (GF < 0.82), [25] and Lipomi et al. investigated spring like structures in the nanotube that reach 150% strain with good conductivity. [22] Ryu et al. showed that aligned CNT fibers grown on flexible substrates were able to stretch out to 900% having GF of up to 47. [42] However, this process required highly ordered alignment of CNT fibers using intricate dry spinning methods. Another aspect to consider for improving wearable strain sensor is the careful selection of the stretchable elastomeric substrate. Many strain sensors have been fabricated using polydimethylsiloxane (PDMS) as the stretchable and flexible substrate due to its flexibility, nontoxicity, ease of fabrication, and biocompatibility. [43,44] Amjadi et al. reported highly flexible, stretchable sensitive strain sensors based on silver nanowires with PDMS that had a GF of 14 at 70% strain. [44] However, many PDMS substrate based strain sensors showed low stretchability with high hysteresis due to poor adhesion between the functional material and substrate polymer, as well as increased friction during the strain. [45,46] Furthermore, PDMS becomes stiffer, delaminates, and slips after absorbing human sweat www.MaterialsViews.com www.advmattechnol.de

Rapid and effective mixing of macromolecular solutions remains a persistent challenge when studyi... more Rapid and effective mixing of macromolecular solutions remains a persistent challenge when studying biochemical reactions. We show here that rapid and enhanced micromixing can be achieved in an easily fabricated (requiring no lithography), topologically simple 3D ...

RSC Advances

A wrinkled gold substrate greatly improves the signaling of electrochemical aptamer-based biosens... more A wrinkled gold substrate greatly improves the signaling of electrochemical aptamer-based biosensors, achieving up to 10-fold increase in signals.

Sensors

The relationship between the robustness of HRV derived by linear and nonlinear methods to the req... more The relationship between the robustness of HRV derived by linear and nonlinear methods to the required minimum data lengths has yet to be well understood. The normal electrocardiography (ECG) data of 14 healthy volunteers were applied to 34 HRV measures using various data lengths, and compared with the most prolonged (2000 R peaks or 750 s) by using the Mann–Whitney U test, to determine the 0.05 level of significance. We found that SDNN, RMSSD, pNN50, normalized LF, the ratio of LF and HF, and SD1 of the Poincaré plot could be adequately computed by small data size (60–100 R peaks). In addition, parameters of RQA did not show any significant differences among 60 and 750 s. However, longer data length (1000 R peaks) is recommended to calculate most other measures. The DFA and Lyapunov exponent might require an even longer data length to show robust results. Conclusions: Our work suggests the optimal minimum data sizes for different HRV measures which can potentially improve the effic...

International Journal of Prognostics and Health Management

Acute injury to aged individuals represents a significant challenge to the global healthcare comm... more Acute injury to aged individuals represents a significant challenge to the global healthcare community as these injuries are frequently treated in a reactive method due to the infeasibility of frequent visits to the hospital for biometric monitoring. However, there is potential to prevent a large number of these cases through passive, at-home monitoring of multiple physiological parameters related to various causes that are common to aged adults in general. This research strives to implement wearable devices, ambient “smart home” devices, and minimally invasive blood and urine analysis to test the feasibility of implementation of a multitude of research-level (i.e. not yet clinically validated) methods simultaneously in a “smart system”. The system comprises measures of balance, breathing, heart rate, metabolic rate, joint flexibility, hydration, and physical performance functions in addition to lab testing related to biological aging and mechanical cell strength. A proof-of-concept...

Analytical Methods

We introduce a simple, scalable, and portable electrochemical aptamer-based system for detection ... more We introduce a simple, scalable, and portable electrochemical aptamer-based system for detection of the SARS-CoV-2 spike protein in saliva with attomolar sensitivity.

Advanced Electronic Materials

Polymers

Soft stretchable sensors rely on polymers that not only withstand large deformations while retain... more Soft stretchable sensors rely on polymers that not only withstand large deformations while retaining functionality but also allow for ease of application to couple with the body to capture subtle physiological signals. They have been applied towards motion detection and healthcare monitoring and can be integrated into multifunctional sensing platforms for enhanced human machine interface. Most advances in sensor development, however, have been aimed towards active materials where nearly all approaches rely on a silicone-based substrate for mechanical stability and stretchability. While silicone use has been advantageous in academic settings, conventional silicones cannot offer self-healing capability and can suffer from manufacturing limitations. This review aims to cover recent advances made in polymer materials for soft stretchable conductors. New developments in substrate materials that are compliant and stretchable but also contain self-healing properties and self-adhesive capab...

Materials

Practical wearable applications of soft strain sensors require sensors capable of not only detect... more Practical wearable applications of soft strain sensors require sensors capable of not only detecting subtle physiological signals, but also of withstanding large scale deformation from body movement. Encapsulation is one technique to protect sensors from both environmental and mechanical stressors. We introduced an encapsulation layer to crack-based wrinkled metallic thin film soft strain sensors as an avenue to improve sensor stretchability, linear response, and robustness. We demonstrate that encapsulated sensors have increased mechanical robustness and stability, displaying a significantly larger linear dynamic range (~50%) and increased stretchability (260% elongation). Furthermore, we discovered that these sensors have post-fracture signal recovery. They maintained conductivity to the 50% strain with stable signal and demonstrated increased sensitivity. We studied the crack formation behind this phenomenon and found encapsulation to lead to higher crack density as the source fo...

Advanced Materials Technologies

npj Digital Medicine

Current methods for continuous respiration monitoring such as respiratory inductive or optoelectr... more Current methods for continuous respiration monitoring such as respiratory inductive or optoelectronic plethysmography are limited to clinical or research settings; most wearable systems reported only measures respiration rate. Here we introduce a wearable sensor capable of simultaneously measuring both respiration rate and volume with high fidelity. Our disposable respiration sensor with a Band-Aid© like formfactor can measure both respiration rate and volume by simply measuring the local strain of the ribcage and abdomen during breathing. We demonstrate that both metrics are highly correlated to measurements from a medical grade continuous spirometer on participants at rest. Additionally, we also show that the system is capable of detecting respiration under various ambulatory conditions. Because these low-powered piezo-resistive sensors can be integrated with wireless Bluetooth units, they can be useful in monitoring patients with chronic respiratory diseases in everyday settings.

Advanced Healthcare Materials

Wrinkled gold thin films on elastomeric substrates are used as robust parallel plate electrodes f... more Wrinkled gold thin films on elastomeric substrates are used as robust parallel plate electrodes for soft capacitive pressure sensors. The wrinkled structures create a robust integration with the polymer, allowing repeated normal force to deform the thin film without failure. By incorporating microridged structures that support the counter electrodes to create air cavities within the elastomeric dielectric layer, pressure sensitivity is further increased to 0.148 kPa-1 over a wide dynamic range of up to 10 kPa. The wide dynamic range and pressure sensitivity of the pressure sensor allow for consistent measurements of the pressure exerted by the radial artery located on the wrist. The soft capacitive pressure sensor displays comparable results when tested against an FDA approved device (Clearsight, Edwards Lifesciences, Irvine, CA) measuring beat-to-beat blood pressure. These soft pressure sensors using wrinkled thin films, therefore, illustrate considerable potential to continuously monitor beat-to-beat blood pressure.

Macromolecular Materials and Engineering

Advanced Materials Technologies

Piezoelectric materials are materials that can produce electrical charges when induced with mecha... more Piezoelectric materials are materials that can produce electrical charges when induced with mechanical stress and have been widely used in pressure sensors. [30] For example, Chen et al. reported vertically aligned piezoelectric P(VDF-TrFE) nanowires that were able to detect blood pulse on the wrist. [12] The device was able to output a maximum of 4.8 V with a current density of 0.11 µA cm −2. These sensors had high response times and limits of detection of less than 2 Pa, but could only provide dynamic information which greatly limits its applications. Capacitive pressure sensors consist of a compliant dielectric layer sandwiched by two parallel conductive electrodes. When a pressure is applied, the dielectric layer gets compressed generating an increase in capacitance. Capacitive pressure sensors have been characterized with high signal linearity, but have low pressure sensitivities. Zhao et al. reported a flexible capacitive array pressure sensor with a pressure sensitivity of 1.45 MPa −1. [4] Yao and Zhu have demonstrated that silver nanowires can also be used to fabricate stretchable conductors allowing for pressure sensitivities of up to 1.62 MPa −1. [31] Zang et al. have also demonstrated that compressible dielectric layers can also be incorporated into organic thin-film transistors (OTFTs) achieving pressure sensitivities of up to 192 kPa −1. [32] While high sensitivities were achieved, the device required high voltages to achieve high sensitivities (V ds = −60 V). Although capacitive pressure sensors exhibit highly linear signal responses, they are generally characterized with poor sensitivity due to the small compression of the dielectric layer. Higher sensitivities can only be achieved by using higher voltage sources. Piezoresistive sensors work by detecting the change in resistance upon actuation. This is typically structured by coupling two conductive rough surfaces together. By doing so, the number of electrical contacts can be changed by the amount of mechanical pressure that is applied, effectively increasing or lowering resistivity between the electrodes. For example, Park et al. fabricated polydimethylsiloxane (PDMS)/carbon nanotube (CNT) composite interlocking microdome surfaces achieving pressure sensitivities of up to 15.1 kPa −1. [33] Rough surfaces could also be made by molding silk textile with CNT/ PDMS composite materials to achieve pressure sensitivities of up to 1.80 kPa −1. [34] Silver nanowire networks have also been Highly sensitive and flexible components are essential for applications in wearable electronics. Using low-cost and rapid prototyping methods, piezoresistive pressure sensors are fabricated using shrink-film, a shape memory polymer that retracts upon heat, to introduce wrinkling in carbon nanotube thin films, which improves both elasticity and pressure sensitivity. The wrinkles not only provide strain relief, but it also improves pressure sensitivity by 12 800 fold with a response time of less than 20 ms. The improved sensitivity is due to the surface roughness of the wrinkles. When two wrinkled electrodes are coupled together, the number of electrical contact points changes upon actuation thereby changing the electrical resistivity. This study then demonstrates wearable applications, such as pulsatile blood flow monitoring and voice detection using these sensitive pressure sensors.

Methods (San Diego, Calif.), Jan 16, 2017

Neural stem cell (NSC) cultures have been considered technically challenging for time-lapse analy... more Neural stem cell (NSC) cultures have been considered technically challenging for time-lapse analysis due to high motility, photosensitivity, and growth at confluent densities. We have tested feasibility of long-term live-cell time-lapse analysis for NSC migration and differentiation studies. Here, we describe a method to study the dynamics of cell cycle, migration, and lineage selection in cultured multipotent mouse or human NSCs using single-cell tracking during a long-term, 7-14 day live-cell time-lapse analysis. We used in-house made PDMS inserts with five microwells on a glass coverslip petri-dish to constrain NSC into the area of acquisition during long-term live-cell imaging. In parallel, we have defined image acquisition settings for single-cell tracking of cell cycle dynamics using Fucci-reporter mouse NSC for 7 days as well as lineage selection and migration using human NSC for 14 days. Overall, we show that adjustments of live-cell analysis settings can extend the time per...

Stem cell reports, Nov 14, 2017

Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a d... more Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge. Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses. As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets. Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space. Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS) electrically paced at a range of frequencies and exposed to a library of compounds. A generated metric is effective for th...

Biofabrication

The vascularization of tissue grafts is critical for maintaining viability of the cells within a ... more The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues.

Optical Materials Express

We demonstrate increased intra-ensemble energy transfer (ET) in monodispersed semiconducting quan... more We demonstrate increased intra-ensemble energy transfer (ET) in monodispersed semiconducting quantum dots (QDs), mediated by localized plasmons on metallic thin films with nano-scale wrinkles. The increased ET results in a net spectral red-shift, up to threefold increase in emission intensity, and a faster radiative recombination rate of the ensemble. The extent of the red-shift is dependent on QD size, and is largest for the QDs where the absorption spectrum overlaps the plasmonic resonance of the film. This effect has a uniform, macroscopic manifestation and may provide an inexpensive option of improving performance of QD based photovoltaic devices.