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Safety is essential for life. To survive, humans and other animals have developed sets of psychological and physiological adaptations known as life history (LH) tradeoff strategies in response to various safety constraints. Evolutionarily selected LH strategies in turn regulate development and behavior to optimize survival under prevailing safety conditions. The present study tested LH hypotheses concerning safety based on a 6-year longitudinal sample of 1,245 adolescents and their parents from 9 countries. The results revealed that, invariant across countries, environmental harshness, and unpredictability (lack of safety) was negatively associated with slow LH behavioral profile, measured 2 years later, and slow LH behavioral profile was negatively and positively associated with externalizing behavior and academic performance, respectively, as measured an additional 2 years later. These results support the evolutionary conception that human development responds to environmental safety cues through LH regulation of social and learning behaviors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Microfluidics is an emerging science and technology that manipulates the fluids in channels of tens of micrometers. It provides better solutions in fields of chemistry, material science and biology. Its versatile applications involve chemical synthesis, separation and analysis, high-throughput drug screening, bioanalysis, cell biology and tissue engineering, etc. However, it still requires a great deal of work to be done in its manufacturing and downstream applications to make it widely and inexpensively available. This PhD thesis focuses on fabrication of microfluidic devices and biomaterial design for biological applications through conducting three independent projects. Herein, I start from a brief introduction of microfluidics including the fabrication of PDMS-based microfluidics devices and several representative applications. After that, I present the research projects during my PhD study: (1) Microneedle arrays using microlens-based UV lithography, and microneedle arrays are applicable for applications in drug delivery; (2) Microfluidic method for on-demand fluid dispensing using a microcreviced membrane, and this fluid dispensing method is readily to be applied in chemical and biological analysis; (3) Self-crosslinkable chitosan hydrogel for in situ cell encapsulation and subsequent 3D cell culture, which is a promising extracellular matrix (ECM) candidate in the field of tissue engineering. Each project is related to biological applications.

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and “body-on-a-chip” and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns. © The Royal Society of Chemistry.

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and “body-on-a-chip” and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns. © The Royal Society of Chemistry.

Microfluidics is an emerging science and technology that manipulates the fluids in channels of tens of micrometers. It provides better solutions in fields of chemistry, material science and biology. Its versatile applications involve chemical synthesis, separation and analysis, high-throughput drug screening, bioanalysis, cell biology and tissue engineering, etc. However, it still requires a great deal of work to be done in its manufacturing and downstream applications to make it widely and inexpensively available. This PhD thesis focuses on fabrication of microfluidic devices and biomaterial design for biological applications through conducting three independent projects. Herein, I start from a brief introduction of microfluidics including the fabrication of PDMS-based microfluidics devices and several representative applications. After that, I present the research projects during my PhD study: (1) Microneedle arrays using microlens-based UV lithography, and microneedle arrays are applicable for applications in drug delivery; (2) Microfluidic method for on-demand fluid dispensing using a microcreviced membrane, and this fluid dispensing method is readily to be applied in chemical and biological analysis; (3) Self-crosslinkable chitosan hydrogel for in situ cell encapsulation and subsequent 3D cell culture, which is a promising extracellular matrix (ECM) candidate in the field of tissue engineering. Each project is related to biological applications.

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and “body-on-a-chip” and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns. © The Royal Society of Chemistry.

Microfluidics is an emerging science and technology that manipulates the fluids in channels of tens of micrometers. It provides better solutions in fields of chemistry, material science and biology. Its versatile applications involve chemical synthesis, separation and analysis, high-throughput drug screening, bioanalysis, cell biology and tissue engineering, etc. However, it still requires a great deal of work to be done in its manufacturing and downstream applications to make it widely and inexpensively available. This PhD thesis focuses on fabrication of microfluidic devices and biomaterial design for biological applications through conducting three independent projects. Herein, I start from a brief introduction of microfluidics including the fabrication of PDMS-based microfluidics devices and several representative applications. After that, I present the research projects during my PhD study: (1) Microneedle arrays using microlens-based UV lithography, and microneedle arrays are applicable for applications in drug delivery; (2) Microfluidic method for on-demand fluid dispensing using a microcreviced membrane, and this fluid dispensing method is readily to be applied in chemical and biological analysis; (3) Self-crosslinkable chitosan hydrogel for in situ cell encapsulation and subsequent 3D cell culture, which is a promising extracellular matrix (ECM) candidate in the field of tissue engineering. Each project is related to biological applications.

The fabrication of microfluidic chips can be simplified and accelerated by three-dimensional (3D) printing. However, all of the current designs of 3D printed microchips require off-chip bulky equipment to operate, which hindered their applications in the point-of-care (POC) setting. In this work, we demonstrate a new class of movable 3D printed microfluidic chip components, including torque-actuated pump and valve, rotary valve, and pushing valve, which can be operated manually without any off-chip bulky equipment such as syringe pump and gas pressure source. By integrating these components, we developed a user-friendly 3D printed chip that can perform general colorimetric assays. Protein quantification was performed on artificial urine samples as a proof-of-concept model with a smartphone used as the imaging platform. The protein was quantified linearly and was within the physiologically relevant range for humans. We believe that the demonstrated components and designs can expand the functionalities and potential applications of 3D printed microfluidic chip and thus provoke more investigation on manufacturing lab-on-a-chip devices by 3D printers.

Fabricating complicated three-dimensional (3D) hydrogel structures are important in biological studies. Herein, stereolithographic printed acrylate-based masters with different complicated 3D geometry (e.g. dodecahedron and a trifurcating network) were replicated into alginate and gelatin. Alginate was further used as a sacrificial template to fabricate a perfusable microfluidic network in cell-seeded agarose to sustain the cell viability in a large slab of agarose scaffold. With the replication approach, 3D alginate (a photo-insensitive material) constructs with stereolithographic (a photolithographic technology) grade resolution and structural complexity were fabricated. © 2016 The Royal Society of Chemistry.

Fabricating complicated three-dimensional (3D) hydrogel structures are important in biological studies. Herein, stereolithographic printed acrylate-based masters with different complicated 3D geometry (e.g. dodecahedron and a trifurcating network) were replicated into alginate and gelatin. Alginate was further used as a sacrificial template to fabricate a perfusable microfluidic network in cell-seeded agarose to sustain the cell viability in a large slab of agarose scaffold. With the replication approach, 3D alginate (a photo-insensitive material) constructs with stereolithographic (a photolithographic technology) grade resolution and structural complexity were fabricated. © 2016 The Royal Society of Chemistry.

The fabrication of microfluidic chips can be simplified and accelerated by three-dimensional (3D) printing. However, all of the current designs of 3D printed microchips require off-chip bulky equipment to operate, which hindered their applications in the point-of-care (POC) setting. In this work, we demonstrate a new class of movable 3D printed microfluidic chip components, including torque-actuated pump and valve, rotary valve, and pushing valve, which can be operated manually without any off-chip bulky equipment such as syringe pump and gas pressure source. By integrating these components, we developed a user-friendly 3D printed chip that can perform general colorimetric assays. Protein quantification was performed on artificial urine samples as a proof-of-concept model with a smartphone used as the imaging platform. The protein was quantified linearly and was within the physiologically relevant range for humans. We believe that the demonstrated components and designs can expand the functionalities and potential applications of 3D printed microfluidic chip and thus provoke more investigation on manufacturing lab-on-a-chip devices by 3D printers.

Fabricating complicated three-dimensional (3D) hydrogel structures are important in biological studies. Herein, stereolithographic printed acrylate-based masters with different complicated 3D geometry (e.g. dodecahedron and a trifurcating network) were replicated into alginate and gelatin. Alginate was further used as a sacrificial template to fabricate a perfusable microfluidic network in cell-seeded agarose to sustain the cell viability in a large slab of agarose scaffold. With the replication approach, 3D alginate (a photo-insensitive material) constructs with stereolithographic (a photolithographic technology) grade resolution and structural complexity were fabricated.

The fabrication of microfluidic chips can be simplified and accelerated by three-dimensional (3D) printing. However, all of the current designs of 3D printed microchips require off-chip bulky equipment to operate, which hindered their applications in the point-of-care (POC) setting. In this work, we demonstrate a new class of movable 3D printed microfluidic chip components, including torque-actuated pump and valve, rotary valve, and pushing valve, which can be operated manually without any off-chip bulky equipment such as syringe pump and gas pressure source. By integrating these components, we developed a user-friendly 3D printed chip that can perform general colorimetric assays. Protein quantification was performed on artificial urine samples as a proof-of-concept model with a smartphone used as the imaging platform. The protein was quantified linearly and was within the physiologically relevant range for humans. We believe that the demonstrated components and designs can expand the functionalities and potential applications of 3D printed microfluidic chip and thus provoke more investigation on manufacturing lab-on-a-chip devices by 3D printers.

Microgrooved thin PLGA film (≈30 μm) is successfully fabricated on a Teflon mold, which could be readily peeled off and is used for the construction of a biomimetic cardiac patch. The contraction of it is studied with optical mapping on transmembrane action potential. Our results suggest that steady-state contraction could be easily established on it under regular electrical stimuli. Besides, the biomimetic cardiac patch recapitulates the anisotropic electrophysiological feature of native cardiac tissue and is much more refractory to premature stimuli than the random one constructed with non-grooved PLGA film, as proved by the reduced incidence of arrhythmia. Considering the good biocompatibility of PLGA as demonstrated in our study and the biodegradability of it, our biomimetic cardiac patch may find applications in the treatment of myocardial infarction. Moreover, the Teflon mold could be applied in the fabrication of various scaffolds with fine features for other tissues.

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 +/- 13.3%) and specificity (24.3 +/- 8.6%) were achieved.

In this paper, we have developed a simple and direct platform to fabricate tapered microneedle (MN) structures using UV lithography based on microlens technique without any complex equipment and sophisticated controls. Utilizing the convex microlens to focusing UV light for inversed SU-8 lithography, microneedle array can be fabricated in SU-8 form in a simple and direct way. The size and shape of tapered microneedle were basically consistent with the theoretical prediction based on focal length of microlens, satisfying the requirements of microneedles commonly used as well. Poly-lactic-co-glycolic acid (PLGA) microneedle patch replicated from negative polydimethylsiloxane (PDMS) master was successfully applied to mouse skin for penetrating test. It proves that microneedle patch can be produced based on microlens technique and has prospective applications in Transdermal drug delivery (TDD) systems. © 15CBMS-0001.

Fabricating hydrogel with arbitrary 3D geometries is challenging. Current additive manufacturing technique developed for hydrogel suffers from low resolution and simple object architecture. Here, by addressing the challenges of mold removal and pores blocking in applying traditional lost-wax casting technique to replicate 3D printed structures into hydrogels, we demonstrate the first replication of 3D structure such as dodecahedron from 3D printed material into alginate and genipin-crosslinked gelatin. Furthermore, we show the fabrication of perfusable, complicated 3D microfluidic network in cell-seeded hydrogel by using the alginate replica as the sacrificial template. © 15CBMS-0001.

In this work, we developed a convenient, one-step soft-lithographic-based molding technique for molding truly 3D microfluidic channels in polydimethylsiloxane (PDMS) by overcoming two grand challenges. We optimized the post-treatment conditions for 3D-printed resin structures to facilitate the use of them as masters for PDMS replica molding. What is more important, we demonstrated a novel method for single-step molding from 3D-printed microstructures to generate truly 3D microfluidic networks easily. With this technique, we fabricated some key, functional 3D microfluidic structures and components including a basket-weaving network, a 3D chaotic advective mixer and microfluidic peristaltic valves. Furthermore, an interesting "injection-on-demand" microfluidic device was also demonstrated. Our technique offers a simple, fast route to the fabrication of 3D microfluidic chips in a short time without clean-room facilities.

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 +/- 13.3%) and specificity (24.3 +/- 8.6%) were achieved.

In this paper, we have developed a simple and direct platform to fabricate tapered microneedle (MN) structures using UV lithography based on microlens technique without any complex equipment and sophisticated controls. Utilizing the convex microlens to focusing UV light for inversed SU-8 lithography, microneedle array can be fabricated in SU-8 form in a simple and direct way. The size and shape of tapered microneedle were basically consistent with the theoretical prediction based on focal length of microlens, satisfying the requirements of microneedles commonly used as well. Poly-lactic-co-glycolic acid (PLGA) microneedle patch replicated from negative polydimethylsiloxane (PDMS) master was successfully applied to mouse skin for penetrating test. It proves that microneedle patch can be produced based on microlens technique and has prospective applications in Transdermal drug delivery (TDD) systems. © 15CBMS-0001.

Fabricating hydrogel with arbitrary 3D geometries is challenging. Current additive manufacturing technique developed for hydrogel suffers from low resolution and simple object architecture. Here, by addressing the challenges of mold removal and pores blocking in applying traditional lost-wax casting technique to replicate 3D printed structures into hydrogels, we demonstrate the first replication of 3D structure such as dodecahedron from 3D printed material into alginate and genipin-crosslinked gelatin. Furthermore, we show the fabrication of perfusable, complicated 3D microfluidic network in cell-seeded hydrogel by using the alginate replica as the sacrificial template. © 15CBMS-0001.

In this work, we developed a convenient, one-step soft-lithographic-based molding technique for molding truly 3D microfluidic channels in polydimethylsiloxane (PDMS) by overcoming two grand challenges. We optimized the post-treatment conditions for 3D-printed resin structures to facilitate the use of them as masters for PDMS replica molding. What is more important, we demonstrated a novel method for single-step molding from 3D-printed microstructures to generate truly 3D microfluidic networks easily. With this technique, we fabricated some key, functional 3D microfluidic structures and components including a basket-weaving network, a 3D chaotic advective mixer and microfluidic peristaltic valves. Furthermore, an interesting "injection-on-demand" microfluidic device was also demonstrated. Our technique offers a simple, fast route to the fabrication of 3D microfluidic chips in a short time without clean-room facilities.

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 +/- 13.3%) and specificity (24.3 +/- 8.6%) were achieved.

Fabricating hydrogel with arbitrary 3D geometries is challenging. Current additive manufacturing technique developed for hydrogel suffers from low resolution and simple object architecture. Here, by addressing the challenges of mold removal and pores blocking in applying traditional lost-wax casting technique to replicate 3D printed structures into hydrogels, we demonstrate the first replication of 3D structure such as dodecahedron from 3D printed material into alginate and genipin-crosslinked gelatin. Furthermore, we show the fabrication of perfusable, complicated 3D microfluidic network in cell-seeded hydrogel by using the alginate replica as the sacrificial template. © 15CBMS-0001.

In this paper, we have developed a simple and direct platform to fabricate tapered microneedle (MN) structures using UV lithography based on microlens technique without any complex equipment and sophisticated controls. Utilizing the convex microlens to focusing UV light for inversed SU-8 lithography, microneedle array can be fabricated in SU-8 form in a simple and direct way. The size and shape of tapered microneedle were basically consistent with the theoretical prediction based on focal length of microlens, satisfying the requirements of microneedles commonly used as well. Poly-lactic-co-glycolic acid (PLGA) microneedle patch replicated from negative polydimethylsiloxane (PDMS) master was successfully applied to mouse skin for penetrating test. It proves that microneedle patch can be produced based on microlens technique and has prospective applications in Transdermal drug delivery (TDD) systems. © 15CBMS-0001.

In this work, we developed a convenient, one-step soft-lithographic-based molding technique for molding truly 3D microfluidic channels in polydimethylsiloxane (PDMS) by overcoming two grand challenges. We optimized the post-treatment conditions for 3D-printed resin structures to facilitate the use of them as masters for PDMS replica molding. What is more important, we demonstrated a novel method for single-step molding from 3D-printed microstructures to generate truly 3D microfluidic networks easily. With this technique, we fabricated some key, functional 3D microfluidic structures and components including a basket-weaving network, a 3D chaotic advective mixer and microfluidic peristaltic valves. Furthermore, an interesting "injection-on-demand" microfluidic device was also demonstrated. Our technique offers a simple, fast route to the fabrication of 3D microfluidic chips in a short time without clean-room facilities.