skip to main content


Search for: All records

Award ID contains: 1647837

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Abstract

    The Casimir force, a quantum mechanical effect, has been observed in several microelectromechanical system (MEMS) platforms. Due to its extreme sensitivity to the separation of two objects, the Casimir force has been proposed as an excellent avenue for quantum metrology. Practical application, however, is challenging due to attractive forces leading to stiction and device failure, called Casimir pull-in. In this work, we design and simulate a Casimir-driven metrology platform, where a time-delay-based parametric amplification technique is developed to achieve a steady-state and avoid pull-in. We apply the design to the detection of weak, low-frequency, gradient magnetic fields similar to those emanating from ionic currents in the heart and brain. Simulation parameters are selected from recent experimental platforms developed for Casimir metrology and magnetic gradiometry, both on MEMS platforms. While a MEMS offers many advantages to such an application, the detected signal must typically be at the resonant frequency of the device, with diminished sensitivity in the low frequency regime of biomagnetic fields. Using a Casimir-driven parametric amplifier, we report a 10,000-fold improvement in the best-case resolution of MEMS single-point gradiometers, with a maximum sensitivity of 6 Hz/(pT/cm) at 1 Hz. Further development of the proposed design has the potential to revolutionize metrology and may specifically enable the unshielded monitoring of biomagnetic fields in ambient conditions.

     
    more » « less
  2. Abstract

    Electrical pacing/stimulations (EP) have been widely adopted to promote the maturation of hiPSC‐derived cardiomyocytes. However, there is a debate about their functions and effectiveness due to non‐optimized pacing conditions. Here, the effectiveness of EP (13 V cm−1, 2 ms in width, and 5 Hz frequency) on cardiac tissue beating mechanics are analyzed using digital image correlation (DIC). The cardiac tissues with and without EP at tissue culture time from day 2 to 11 (D2–D11) are characterized and compared. The results indicate EP decreased cardiac beating motion for ≈2–15 times, promote synchronization, and improve ion handling. A positive correlation between cardiac beating mechanics and ion handling is observed. DIC method can optimize chemical, mechanical, and electrical stimulation, which could help create more mature cardiac tissues.

     
    more » « less
  3. Abstract

    Direct laser writing (DLW) via two‐photon polymerization is an emerging highly precise technique for the fabrication of intricate cellular scaffolds. Despite recent progress in using two‐photon‐polymerized scaffolds to probe fundamental cell behaviors, new methods to direct and modulate microscale cell alignment and selective cell adhesion using two‐photon‐polymerized microstructures are of keen interest. Here, a DLW‐fabricated 2D and 3D hydrogel microstructures, with alternating soft and stiff regions, for precisely controlled cell alignment are reported. The use of both cell‐adhesive and cell‐repellent hydrogels allows selective adhesion and alignment of human mesenchymal stem cells within the printed structure. Importantly, DLW patterning enables cell alignment on flat surfaces as well as irregular and curved 3D microstructures, which are otherwise challenging to pattern with cells.

     
    more » « less
  4. Abstract

    The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. The contractile force is found to correlate with both the scattering intensity (R2 = 0.44) and lattice spacing (R2 = 0.46). The scattering intensity also correlates with lattice spacing (R2 = 0.81), suggestive of lower noise in our structural measurement than in the functional measurement. Notably, we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.

     
    more » « less
  5. Abstract

    Diagnostic testing that facilitates containment, surveillance, and treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), or future respiratory viruses, depends on a sample collection device that efficiently collects nasopharyngeal tissue and that can be manufactured on site when an outbreak or public health emergency is declared by a government. Here two novel stereolithography‐based three‐dimensional (3D)‐printed nasopharyngeal swabs are reported which are made using a biocompatible and sterilizable photoresist. Such swabs are readily manufactured on‐site and on‐demand to ensure availability, if supply chain shortages emerge. Additionally, the 3D‐printed swabs easily adapt to current workflow and testing procedures in hospital clinical laboratories to allow for effortless scaling up of test kits. Finally, the 3D‐printed nasopharyngeal swabs demonstrate concordant SARS‐CoV‐2 testing results between the 3D‐printed swabs and the COPAN commercial swabs, and enable detection of SARS‐CoV‐2 in clinical samples obtained from autopsies.

     
    more » « less
  6. Abstract

    From microscaled capillaries to millimeter‐sized vessels, human vasculature spans multiple scales and cell types. The convergence of bioengineering, materials science, and stem cell biology has enabled tissue engineers to recreate the structure and function of different hierarchical levels of the vascular tree. Engineering large‐scale vessels aims to replace damaged arteries, arterioles, and venules and their routine application in the clinic may become a reality in the near future. Strategies to engineer meso‐ and microvasculature are extensively explored to generate models for studying vascular biology, drug transport, and disease progression as well as for vascularizing engineered tissues for regenerative medicine. However, bioengineering tissues for transplantation has failed to result in clinical translation due to the lack of proper integrated vasculature for effective oxygen and nutrient delivery. The development of strategies to generate multiscale vascular networks and their direct anastomosis to host vasculature would greatly benefit this formidable goal. In this review, design considerations and technologies for engineering millimeter‐, meso‐, and microscale vessels are discussed. Examples of recent state‐of‐the‐art strategies to engineer multiscale vasculature are also provided. Finally, key challenges limiting the translation of vascularized tissues are identified and perspectives on future directions for exploration are presented.

     
    more » « less
  7. Abstract

    A major goal of environmental agencies today is to conduct point-of-collection monitoring of excess inorganic phosphate (Pi) in environmental water samples for tracking aquatic “dead zones” caused by algae blooms. However, there are no existing commercial devices which have been miniaturized and are suitable for the point-of-need-testing (“PONT”) that is required to fully map a large region, such as the Florida Everglades. To solve this challenge, a reflection-mode fluorescence-sensing apparatus was developed, leveraging an environmentally sensitive fluorophore (MDCC) bound to a bacterial phosphate-binding protein to generate a fluorescent optical signal proportional to the concentration of (Pi) present. The combined end-to-end integrated sensor system had a response time of only 4 s, with minimal effects of common interfering agents and a linear range spanning from 1.1 to 64 ppb. To support ease-of-use during PONT, the platform incorporated disposable wax-printed paper strip sample pads and a smartphone camera detection system. Since the EPA threshold is currently 30 ppb to prevent eutrophication, this system serves as a rapid test of whether a region is compliant.

     
    more » « less
  8. Abstract

    Direct laser writing via two‐photon polymerization (2PP) is an emerging micro‐ and nanofabrication technique to prepare predetermined and architecturally precise hydrogel scaffolds with high resolution and spatial complexity. As such, these scaffolds are increasingly being evaluated for cell and tissue engineering applications. This article first discusses the basic principles and photoresists employed in 2PP fabrication of hydrogels, followed by an in‐depth introduction of various mechanical and biological characterization techniques used to assess the fabricated structures. The design requirements for cell and tissue related applications are then described to guide the engineering, physicochemical, and biological efforts. Three case studies in bone, cancer, and cardiac tissues are presented that illustrate the need for structured materials in the next generation of clinical applications. This paper concludes by summarizing the progress to date, identifying additional opportunities for 2PP hydrogel scaffolds, and discussing future directions for 2PP research.

     
    more » « less
  9. Abstract

    Synthetic biological systems are used for a myriad of applications, including tissue engineered constructs for in vivo use and microengineered devices for in vitro testing. Recent advances in engineering complex biological systems have been fueled by opportunities arising from the combination of bioinspired materials with biological and computational tools. Driven by the availability of large datasets in the “omics” era of biology, the design of the next generation of tissue equivalents will have to integrate information from single‐cell behavior to whole organ architecture. Herein, recent trends in combining multiscale processes to enable the design of the next generation of biomaterials are discussed. Any successful microprocessing pipeline must be able to integrate hierarchical sets of information to capture key aspects of functional tissue equivalents. Micro‐ and biofabrication techniques that facilitate hierarchical control as well as emerging polymer candidates used in these technologies are also reviewed.

     
    more » « less
  10. Abstract

    Chemical heterogeneity on biomaterial surfaces can transform its interfacial properties, rendering nanoscale heterogeneity profoundly consequential during bioadhesion. To examine the role played by chemical heterogeneity in the adsorption of viruses on synthetic surfaces, a range of novel coatings is developed wherein a tunable mixture of electrostatic tethers for viral binding, and carbohydrate brushes, bearing pendant α‐mannose, β‐galactose, or β‐glucose groups, is incorporated. The effects of binding site density, brush composition, and brush architecture on viral adsorption, with the goal of formulating design specifications for virus‐resistant coatings are experimentally evaluated. It is concluded that virus‐coating interactions are shaped by the interplay between brush architecture and binding site density, after quantifying the adsorption of adenoviruses, influenza, and fibrinogen on a library of carbohydrate brushes co‐immobilized with different ratios of binding sites. These insights will be of utility in guiding the design of polymer coatings in realistic settings where they will be populated with defects.

     
    more » « less