Utkan Demirci, Postdoctoral Faculty Sponsor
- Volbots: Volvox Microalgae-Based Robots for Multimode Precision Imaging and Therapy ADVANCED FUNCTIONAL MATERIALS 2022
Acoustic Fabrication of Living Cardiomyocyte-based Hybrid Biorobots.
Organized assemblies of cells have demonstrated promise as bioinspired actuators and devices; still, the fabrication of such "biorobots" has predominantly relied on passive assembly methods that reduce design capabilities. To address this, we have developed a strategy for the rapid formation of functional biorobots composed of live cardiomyocytes. We employ tunable acoustic fields to facilitate the efficient aggregation of millions of cells into high-density macroscopic architectures with directed cell orientation and enhanced cell-cell interaction. These biorobots can perform actuation functions both through naturally occurring contraction-relaxation cycles and through external control with chemical and electrical stimuli. We demonstrate that these biorobots can be used to achieve controlled actuation of a soft skeleton and pumping of microparticles. The biocompatible acoustic assembly strategy described here should prove generally useful for cellular manipulation in the context of tissue engineering, soft robotics, and other applications.
View details for DOI 10.1021/acsnano.2c01908
View details for PubMedID 35671037
- Robotic Pill for Biomarker and Fluid Sampling in the Gastrointestinal Tract ADVANCED INTELLIGENT SYSTEMS 2022
Smart Materials for Microrobots.
2022; 122 (5): 5365-5403
Over the past 15 years, the field of microrobotics has exploded with many research groups from around the globe contributing to numerous innovations that have led to exciting new capabilities and important applications, ranging from in vivo drug delivery, to intracellular biosensing, environmental remediation, and nanoscale fabrication. Smart responsive materials have had a profound impact on the field of microrobotics and have imparted small-scale robots with new functionalities and distinct capabilities. We have identified four large categories where the majority of future efforts must be allocated to push the frontiers of microrobots and where smart materials can have a major impact on such future advances. These four areas are the propulsion and biocompatibility of microrobots, the cooperation between individual units and human operators, and finally, the intelligence of microrobots. In this Review, we look critically at the latest developments in these four categories and discuss how smart materials contribute to the progress in the exciting field of microrobotics and will set the stage for the next generation of intelligent and programmable microrobots.
View details for DOI 10.1021/acs.chemrev.0c00999
View details for PubMedID 33522238
Advanced Point-of-Care Testing Technologies for Human Acute Respiratory Virus Detection.
Advanced materials (Deerfield Beach, Fla.)
The ever-growing global threats to human life caused by the human acute respiratory virus (RV) infections have cost billions of lives, created a significant economic burden, and shaped society for centuries. The timely response to emerging RVs could save human lives and reduce the medical care burden. The development of RV detection technologies is essential for potentially preventing RV pandemic and epidemics. However, commonly used detection technologies lack sensitivity, specificity, and speed, thus often failing to provide the rapid turnaround times. To address this problem, new technologies are devised to address the performance inadequacies of the traditional methods. These emerging technologies offer improvements in convenience, speed, flexibility, and portability of point-of-care test (POCT). Herein, recent developments in POCT are comprehensively reviewed for eight typical acute respiratory viruses. This review discusses the challenges and opportunities of various recognition and detection strategies and discusses these according to their detection principles, including nucleic acid amplification, optical POCT, electrochemistry, lateral flow assays, microfluidics, enzyme-linked immunosorbent assays, and microarrays. The importance of limits of detection, throughput, portability, and specificity when testing clinical samples in resource-limited settings is emphasized. Finally, the evaluation of commercial POCT kits for both essential RV diagnosis and clinical-oriented practices is included.
View details for DOI 10.1002/adma.202103646
View details for PubMedID 34623709
Reversible Design of Dynamic Assemblies at Small Scales.
Advanced intelligent systems (Weinheim an der Bergstrasse, Germany)
2021; 3 (4)
Emerging bottom-up fabrication methods have enabled the assembly of synthetic colloids, microrobots, living cells, and organoids to create intricate structures with unique properties that transcend their individual components. This review provides an access point to the latest developments in externally driven assembly of synthetic and biological components. In particular, we emphasize reversibility, which enables the fabrication of multiscale systems that would not be possible under traditional techniques. Magnetic, acoustic, optical, and electric fields are the most promising methods for controlling the reversible assembly of biological and synthetic subunits since they can reprogram their assembly by switching on/off the external field or shaping these fields. We feature capabilities to dynamically actuate the assembly configuration by modulating the properties of the external stimuli, including frequency and amplitude. We describe the design principles which enable the assembly of reconfigurable structures. Finally, we foresee that the high degree of control capabilities offered by externally driven assembly will enable broad access to increasingly robust design principles towards building advanced dynamic intelligent systems.
View details for DOI 10.1002/aisy.202000193
View details for PubMedID 35663639
View details for PubMedCentralID PMC9165726
- Reversible Design of Dynamic Assemblies at Small Scales ADVANCED INTELLIGENT SYSTEMS 2021; 3 (4)
Emerging biofabrication approaches for gastrointestinal organoids towards patient specific cancer models.
Tissue engineered organoids are simple biomodels that can emulate the structural and functional complexity of specific organs. Here, we review developments in three-dimensional (3D) artificial cell constructs to model gastrointestinal dynamics towards cancer diagnosis. We describe bottom-up approaches to fabricate close-packed cell aggregates, from the use of biochemical and physical cues to guide the self-assembly of organoids, to the use of engineering approaches, including 3D printing/additive manufacturing and external field-driven protocols. Finally, we outline the main challenges and possible risks regarding the potential translation of gastrointestinal organoids from laboratory settings to patient-specific models in clinical applications.
View details for DOI 10.1016/j.canlet.2021.01.023
View details for PubMedID 33577978
Designer exosomes enabling tumor targeted efficient chemo/gene/photothermal therapy.
2021; 276: 121056
Exosomes, endogenous nanosized particles (50-150 nm) secreted and absorbed by cells, have been recently used as diagnostic and therapeutic platforms in cancer treatment. The integration of exosome-based delivery with multiple therapeutic modalities could result in better clinical outcomes and reduced-sided effects. Here, we combined the targeting and biocompatibility of designer exosomes with chemo/gene/photothermal therapy. Our platform consists of exosomes loaded with internalized doxorubicin (DOX, a model cancer drug) and coated with magnetic nanoparticles conjugated with molecular beacons capable of targeting miR-21 for responsive molecular imaging. The coated magnetic nanoparticle enables enrichment of the exosomes at the tumor site by external magnetic field guidance. After the exosomes are gathered at the tumor site, the application of near-infrared radiation (NIR) induces localized hyperthermia and triggers the release of cargoes loaded inside the exosome. The released molecular beacon can target the miR-21 for both imaging and gene silencing. Meanwhile, the released doxorubicin serves to kill the cancer cells. About 91.04 % of cancer cells are killed after treatment with Exo-DOX-Fe3O4@PDA-MB under NIR. The ability of the exosome-based method for cancer therapy has been demonstrated by animal models, in which the tumor size is reduced dramatically by 97.57 % with a magnetic field-guided tumor-targeted chemo/gene/photothermal approach. Thus, we expected this designer exosome-mediated multi-mode therapy to be a promising platform for the next-generation precision cancer nanomedicines.
View details for DOI 10.1016/j.biomaterials.2021.121056
View details for PubMedID 34364178
Wearable Collector for Noninvasive Sampling of SARS-CoV-2 from Exhaled Breath for Rapid Detection.
ACS applied materials & interfaces
Airborne transmission of exhaled virus can rapidly spread, thereby increasing disease progression from local incidents to pandemics. Due to the COVID-19 pandemic, states and local governments have enforced the use of protective masks in public and work areas to minimize the disease spread. Here, we have leveraged the function of protective face coverings toward COVID-19 diagnosis. We developed a user-friendly, affordable, and wearable collector. This noninvasive platform is integrated into protective masks toward collecting airborne virus in the exhaled breath over the wearing period. A viral sample was sprayed into the collector to model airborne dispersion, and then the enriched pathogen was extracted from the collector for further analytical evaluation. To validate this design, qualitative colorimetric loop-mediated isothermal amplification, quantitative reverse transcription polymerase chain reaction, and antibody-based dot blot assays were performed to detect the presence of SARS-CoV-2. We envision that this platform will facilitate sampling of current SARS-CoV-2 and is potentially broadly applicable to other airborne diseases for future emerging pandemics.
View details for DOI 10.1021/acsami.1c09309
View details for PubMedID 34428374
Engineering Polysaccharide-Based Hydrogel Photonic Constructs: From Multiscale Detection to the Biofabrication of Living Optical Fibers.
Advanced materials (Deerfield Beach, Fla.)
Solid-state optics has been the pillar of modern digital age. Integrating soft hydrogel materials with micro/nanooptics could expand the horizons of photonics for bioengineering. Here, wet-spun multilayer hydrogel fibers are engineered through ionic-crosslinked natural polysaccharides that serve as multifunctional platforms. The resulting flexible hydrogel structure and reversible crosslinking provide tunable design properties such as adjustable refractive index and fusion splicing. Modulation of the optical readout via physical stimuli, including shape, compression, and multiple optical inputs/outputs is demonstrated. The unique permeability of the hydrogels is also combined with plasmonic nanoparticles for molecular detection of SARS-CoV-2 in fiber-coupled biomedical swabs. A tricoaxial 3D printing nozzle is then employed for the continuous fabrication of living optical fibers. Light interaction with living cells enables the quantification and digitalization of complex biological phenomena such as 3D cancer progression and drug susceptibility. These fibers pave the way for advances in biomaterial-based photonics and biosensing platforms.
View details for DOI 10.1002/adma.202105361
View details for PubMedID 34617338
Progress and challenges in biomarker enrichment for cancer early detection
Progress in Biomedical Engineering
2021; 3 (4)
View details for DOI 10.1088/2516-1091/ac1ea3
Increasing Diversity in Radiology and Molecular Imaging: Current Challenges.
Molecular imaging and biology
This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9-11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, "racial diversity in STEM," "women in STEM," and "global health," which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare.
View details for DOI 10.1007/s11307-021-01610-3
View details for PubMedID 33903986
Engineering the Interaction Dynamics between Nano-Topographical Immunocyte-Templated Micromotors across Scales from Ions to Cells.
Small (Weinheim an der Bergstrasse, Germany)
Manufacturing mobile artificial micromotors with structural design factors, such as morphology nanoroughness and surface chemistry, can improve the capture efficiency through enhancing contact interactions with their surrounding targets. Understanding the interplay of such parameters targeting high locomotion performance and high capture efficiency at the same time is of paramount importance, yet, has so far been overlooked. Here, an immunocyte-templated nano-topographical micromotor is engineered and their interactions with various targets across multiple scales, from ions to cells are investigated. The macrophage templated nanorough micromotor demonstrates significantly increased surface interactions and significantly improved and highly efficient removal of targets from complex aqueous solutions, including in plasma and diluted blood, when compared to smooth synthetic material templated micromotors with the same size and surface chemistry. These results suggest that the surface nanoroughness of the micromotors for the locomotion performance and interactions with the multiscale targets should be considered simultaneously, for they are highly interconnected in design considerations impacting applications across scales.
View details for DOI 10.1002/smll.202005185
View details for PubMedID 33174334
Medical Micro/Nanorobots in Precision Medicine
Medical Micro/Nanorobots in Precision Medicine
View details for DOI 10.1002/advs.202002203