Enhanced differentiation of human embryonic stem cells towards definitive endoderm on ultrahigh aspect ratio nanopillars

Differentiation of human embryonic stem cells is widely studied as a potential unlimited source for cell replacement therapy to treat degenerative diseases such as diabetes. The directed differentiation of human embryonic stem cells relies mainly on soluble factors. Although, some studies have highlighted that the properties of the physical environment, such as substrate stiffness, affect cellular behavior. Here, mass-produced, injection molded polycarbonate nanopillars are presented, where the surface mechanical properties, i.e., stiffness, can be controlled by the geometric design of the ultrahigh aspect ratio nanopillars (stiffness can be reduced by 25.0003). It is found that tall nanopillars, yielding softer surfaces, significantly enhance the induction of definitive endoderm cells from pluripotent human embryonic stem cells, resulting in more consistent differentiation of a pure population compared to planar control. By contrast, further differentiation toward the pancreatic ­endoderm is less successful on “soft” pillars when compared to “stiff” pillars or control, indicating differential cues during the different stages of differentiation. To accompany the mechanical properties of the nanopillars, the concept of surface shear modulus is introduced to describe the characteristics of engineered elastic surfaces through micro or nanopatterning. This provides a framework whereby comparisons can be drawn between such materials and bulk elastomeric materials

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Recursive Least Squares Filtering Algorithms for On-Line Viscoelastic Characterization of Biosamples

The mechanical characterization of biological samples is a fundamental issue in biology and related fields, such as tissue and cell mechanics, regenerative medicine and diagnosis of diseases. In this paper, a novel approach for the identification of the stiffness and damping coefficients of biosamples is introduced. According to the proposed method, a MEMS-based microgripper in operational condition is used as a measurement tool. The mechanical model describing the dynamics of the gripper-sample system considers the pseudo-rigid body model for the microgripper, and the Kelvin–Voigt constitutive law of viscoelasticity for the sample. Then, two algorithms based on recursive least square (RLS) methods are implemented for the estimation of the mechanical coefficients, that are the forgetting factor based RLS and the normalised gradient based RLS algorithms. Numerical simulations are performed to verify the effectiveness of the proposed approach. Results confirm the feasibility of the method that enables the ability to perform simultaneously two tasks: sample manipulation and parameters identification

Microneedle Mediated Vaccine Delivery: A Comprehensive Review

Microneedles can be representative for paradigm shift of drug delivery from patient non-compliant parenteral injections to patient compliant drug delivery system, which can be utilized for administration of vaccines particularly along with macromolecular/micromolecular drugs. The concept of microneedles came into existence many decades ago but the use of microneedles to achieve efficient delivery of drugs into the skin became subject of research from mid of 1990’s. Various types of microneedles were utilized to enhance delivery of drugs and vaccines including solid microneedles for pre-treatment of skin to enhance drug permeability, dissolvable polymeric microneedles encapsulating drugs, microneedles coated with drugs and hollow microneedles for infusion of drugs through the skin. Microneedles have shown promisingdelivery of vaccines through skin in literature. But the successful utilization of this system for vaccine drug delivery mainly depends on design of device to facilitate microneedle infusion, vaccine stability and storage in system, recovery of skin on removal of microneedle and improved patient compliance. This article reviews the conventional and advanced methods of vaccine drug deliver, microneedles for drug delivery, types of microneedles, advantages of microneedles and potential of microneedles for vaccine drug delivery

ITR/PE+SY digital clay for shape input and display

Issued as final reportNational Science Foundatio

Functional surface microstructures inspired by nature : From adhesion and wetting principles to sustainable new devices

In the course of evolution nature has arrived at startling materials solutions to ensure survival. Investigations into biological surfaces, ranging from plants, insects and geckos to aquatic animals, have inspired the design of intricate surface patterns to create useful functionalities. This paper reviews the fundamental interaction mechanisms of such micropatterns with liquids, solids, and soft matter such as skin for control of wetting, self-cleaning, anti-fouling, adhesion, skin adherence, and sensing. Compared to conventional chemical strategies, the paradigm of micropatterning enables solutions with superior resource efficiency and sustainability. Associated applications range from water management and robotics to future health monitoring devices. We finally provide an overview of the relevant patterning methods as an appendix

Functional surface microstructures inspired by nature – From adhesion and wetting principles to sustainable new devices

In the course of evolution nature has arrived at startling materials solutions to ensure survival. Investigations into biological surfaces, ranging from plants, insects and geckos to aquatic animals, have inspired the design of intricate surface patterns to create useful functionalities. This paper reviews the fundamental interaction mechanisms of such micropatterns with liquids, solids, and soft matter such as skin for control of wetting, self-cleaning, anti-fouling, adhesion, skin adherence, and sensing. Compared to conventional chemical strategies, the paradigm of micropatterning enables solutions with superior resource efficiency and sustainability. Associated applications range from water management and robotics to future health monitoring devices. We finally provide an overview of the relevant patterning methods as an appendix

Dissolving microneedles for cutaneous drug and vaccine delivery

Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues. Microneedles are micron-size needles that deliver drugs or biopharmaceuticals into skin by creating tiny channels in the skin. This thesis focuses on dissolving microneedles in which the needle tips dissolve and release the encapsulated drug or vaccine upon insertion. The project aimed to (i) design and optimize dissolving microneedles for efficient drug and vaccine delivery to the skin, (ii) maintain vaccine stability over long-term storage, and (iii) immunize animals using vaccine encapsulated microneedles. The results showed that influenza vaccine encapsulated in microneedles was more thermally stable than unprocessed vaccine solution over prolonged periods of storage time. In addition, mice immunized with microneedles containing influenza vaccine offered full protection against lethal influenza virus infection. As a result, we envision the newly developed dissolving microneedle system can be a safe, patient compliant, easy to-use and self-administered method for rapid drug and vaccine delivery to the skin.Ph.D.Committee Chair: Prausnitz, Mark; Committee Member: Compans, Richard; Committee Member: Milam, Valeria; Committee Member: Murthy, Niren; Committee Member: Weniger, Bruc

Bioanalytical applications of microfluidic devices

The first part of the thesis describes a new patterning technique--microfluidic contact printing--that combines several of the desirable aspects of microcontact printing and microfluidic patterning and addresses some of their important limitations through the integration of a track-etched polycarbonate (PCTE) membrane. Using this technique, biomolecules (e.g., peptides, polysaccharides, and proteins) were printed in high fidelity on a receptor modified polyacrylamide hydrogel substrate. The patterns obtained can be controlled through modifications of channel design and secondary programming via selective membrane wetting. The protocols support the printing of multiple reagents without registration steps and fast recycle times. The second part describes a non-enzymatic, isothermal method to discriminate single nucleotide polymorphisms (SNPs). SNP discrimination using alkaline dehybridization has long been neglected because the pH range in which thermodynamic discrimination can be done is quite narrow. We found, however, that SNPs can be discriminated by the kinetic differences exhibited in the dehybridization of PM and MM DNA duplexes in an alkaline solution using fluorescence microscopy. We combined this method with multifunctional encoded hydrogel particle array (fabricated by stop-flow lithography) to achieve fast kinetics and high versatility. This approach may serve as an effective alternative to temperature-based method for analyzing unamplified genomic DNA in point-of-care diagnostic