Utkan Demirci's research while affiliated with Stanford University and other places
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Publications (403)
Label-free detection and digital counting of nanometer-scaled objects such as nanoparticles, viruses, extracellular vesicles, and protein molecules enable a wide range of applications in cancer diagnostics, pathogen detection, and life science research. Here, we report the design, implementation, and characterization of a compact Photonic Resonator...
The ability to self-test for HIV is vital to preventing transmission, particularly when used in concert with HIV biomedical prevention modalities, such as pre-exposure prophylaxis (PrEP). In this paper, we review recent developments in HIV self-testing and self-sampling methods, and the potential future impact of novel materials and methods that em...
Exosomes, nano‐sized extracellular vesicles (EVs) secreted from cells, carry various cargo molecules reflecting their cells of origin. As EV content, structure, and size are highly heterogeneous, their classification via cargo molecules by determining their origin is challenging. Here, a method is presented combining surface‐enhanced Raman spectros...
p class="Abstract" style="margin: 0in 0in 30pt; text‐align: justify; line‐height: 11.25pt; font‐size: 8pt; font‐family: Arial, sans‐serif; caret‐color: rgb(0, 0, 0); color: rgb(0, 0, 0);"> Exosomal microRNAs (miRNAs) have considerable potential as pivotal biomarkers to monitor cancer development, dis‐ease progression, treatment effects and prognosi...
Exosomal microRNAs (miRNAs) have considerable potential as pivotal biomarkers to monitor cancer development, dis-ease progression, treatment effects and prognosis. Here, we report an efficient target recycling amplification process (TRAP) for the digital detection of miRNAs using photonic resonator absorption microscopy. We achieve multiplex digita...
Label-free detection and digital counting of nanometer-scaled objects such as nanoparticles, viruses, extracellular vesicles, and protein molecules enable a wide range of applications in cancer diagnostics, pathogen detection, and life science research. The contrast of interferometric scattering microscopy is amplified through a photonic crystal su...
Exosomal microRNAs (miRNAs) have considerable potential as pivotal biomarkers to monitor cancer development, dis-ease progression, treatment effects and prognosis. Here, we report an efficient target recycling amplification process (TRAP) for the digital detection of exosomal miRNAs using photonic resonator absorption microscopy (PRAM). Through toe...
The ability to understand whether embryos survive the thaw process is crucial to transferring competent embryos that can lead to pregnancy. The objective of this study was to develop a proof of concept deep learning model capable of assisting embryologist assessment of survival of thawed blastocysts prior to embryo transfer. A deep learning model w...
Emerging acoustic bioassembly represents an attractive strategy to build cellular closely-packed organotypic constructs in a tunable manner for biofabrication. However, simultaneously assemble heterogenous cell types into heterocellular functional units with spatially-defined cell arrangements, such as complementary and sandwich cytoarchitectures,...
Complex nanoparticles with hybrid forms of quantum dots and nano-scale templates are highly interesting due to various functionalities and broad applications in point-of-care testing (POCT). High sensitivity and throughput are significant for POCT in clinical applications and food safety, especially for determining multiple targets in complex matri...
Plasmonic metasurfaces consist of metal-dielectric interfaces that are excitable at background and leakage resonant modes. The sharp and plasmonic excitation profile of metal-free electrons on metasurfaces at the nanoscale can be used for practical applications in diverse fields, including optoelectronics, energy harvesting, and biosensing. Current...
Ovarian cancer is the most lethal gynecologic malignancy with a stubborn mortality rate of ~65%. The persistent failure of multi-line chemotherapy, and significant tumor heterogeneity, have made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and...
The ability to understand whether embryos survive the thaw process is crucial to transferring competent embryos that can lead to pregnancy. The objective of this study was to develop a deep learning model capable of assisting embryologist assessment of survival of thawed blastocysts prior to embryo transfer. A deep learning model was developed usin...
In many malaria‐endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated p...
Recent breakthroughs in biofabrication of bioasemblies, consisting of the engineered structures composed of biological or biosynthetic components into a single construct, have found a wide range of practical applications in medicine and engineering. This review presents an overview of how the bottom-up assembly of living entities could drive advanc...
RAS genes are the most frequently mutated oncogenes in cancer, yet the effects of oncogenic RAS signaling on the noncoding transcriptome remain unclear. We analyzed the transcriptomes of human airway and bronchial epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We find that oncogenic KRAS sign...
Biohybrid microrobotics are exploited as a delivery approach to actively transport therapeutic payload to tumors. However, the therapeutic utility of this approach can be diminished by tumor hypoxia. Moreover, current biohybrid microrobotics design is mainly focused on the living organisms’ motility and biocompatibility, yet the unique biological f...
Rationale:
The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear.
Objectives:
Relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling.
Methods:
Production of elastase,...
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....
Developing on‐site biomarker enrichment platforms could help to improve the diagnosis of gastrointestinal (GI) tract diseases at early stages. Medical procedures, such as colonoscopies and imaging techniques, are used to diagnose a disease, but are not easily accessible for repeat measurements. In contrast, liquid biopsies, e.g., blood, urine, or f...
Extracellular RNAs (exRNAs) are actively secreted from cells in membrane-bound extracellular vesicles (EVs). Diverse classes of RNAs are secreted as exRNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and transposable element RNAs (TE RNAs). However, the full composition and clinical utility of exRNAs secreted in response to on...
Developing on-site biomarker enrichment platforms could help to improve the diagnosis of gastrointestinal (GI) tract diseases at early stages. Medical procedures, such as colonoscopies and imaging techniques, are used to diagnose disease, but are not easily accessible for repeat measurements. In the other hand, liquid biopsies, e.g. , blood, urine,...
Extracellular vesicles (EVs) have gained considerable attention as vital circulating biomarkers since their structure and composition resemble the originating cells. The investigation of EVs’ biochemical and biophysical properties is of great importance to map them to their parental cells and to better understand their functionalities. In this stud...
In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips....
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...
Digitalizing Biology
The living hydrogel optical fibers and polysaccharide-based photonic constructs fabricated by Rui L. Reis, Utkan Demirci, and co-workers in article number 2105361 are highly versatile and enable the screening of multiscale phenomena, from macro-level forces and shapes to nano-level biotarget detection. Living optical interactio...
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...
Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades...
Cancer cells generate and secrete diverse molecules into circulation that could be used as signatures for health and disease. A significant obstacle in detecting such molecules derives from their low signal-to-noise ratio in subsequent downstream analyses. Developing reliable tools and methods for cancer early detection is crucial for advancing glo...
Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical ve...
Background
Anthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute–sponsored study, but the mechanisms underpinning efficacy in human tissue need...
Light guiding and manipulation in photonics have become ubiquitous in events ranging from everyday communications to complex robotics and nanomedicine. The speed and sensitivity of light-matter interactions offer unprecedented advantages in biomedical optics, data transmission, photomedicine, and detection of multi-scale phenomena. Recently, hydrog...
Biophysical separation promises label-free, less-invasive methods to manipulate the diverse properties of live cells, such as density, magnetic susceptibility, and morphological characteristics. However, some cellular changes are so minute that they are undetectable by current methods. We developed a multiparametric cell-separation approach to prof...
COVID-19, a highly transmissible pandemic disease, affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save the lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development in...
Exosomes are a class of cell-secreted, nano-sized extracellular vesicles with a bilayer membrane structure of 30–150 nm in diameter. Their discovery and application have brought breakthroughs in numerous areas, such as liquid biopsies, cancer biology, drug delivery, immunotherapy, tissue repair, and cardiovascular diseases. Isolation of exosomes is...
Introduction:
Coronavirus disease 2019 (COVID-19), a respiratory illness caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its first detection in December 2019 in Wuhan (China) and spread across the world. In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic disease. The utilization of prom...
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...
Intestinal transplantation is the most effective treatment for patients with short bowel syndrome and small bowel insufficiencies. We evaluated epithelial chimerism after infusion of autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing cadaveric donor isolated intestinal transplantation (I-ITx). BMSCs were isolated from p...
In article number 2000048, Vasif Hasirci, Ezgi Antmen, and Utkan Demirci present micropatterned surfaces that reveal the association between actin filaments, mechanotransduction, nuclear deformability, and cancer malignancy. The transparent micropatterned surfaces can be used as image analysis platforms to provide robust, high throughput measuremen...
Neutrophil elastase (NE) is implicated in pulmonary arterial hypertension (PAH) but the role of neutrophils in the pathogenesis of PAH is unclear. Here we show that neutrophils from PAH vs. control subjects produce and release increased NE associated with enhanced extracellular trap formation. PAH neutrophils are highly adherent and show decreased...
Mechanotransduction proteins transfer mechanical stimuli through nucleo‐cytoskeletal coupling and affect the nuclear morphology of cancer cells. However, the contribution of actin filament integrity has never been studied directly. It is hypothesized that differences in nuclear deformability of cancer cells are influenced by the integrity of actin...
In article number 2005185, Utkan Demirci and co‐workers present living immunocyte templated micromotors that demonstrate significantly increased surface interactions and efficient removal of various targets across multiple scales, from ions to cells, compared to smooth synthetic material templated micromotors with the same size and surface chemistr...
Rapid and efficient processing of sexual assault evidence will accelerate forensic investigation and decrease casework backlogs. The standardized protocols currently used in forensic laboratories require continued innovation to handle the increasing number and complexity of samples being submitted to forensic labs. Here, we present a new technique...
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. Herein, an access point to the latest developments is provided in externally driven assembly of synthetic and biological co...
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...
Exosomes are small particles secreted from cells through an endosomal sorting complexes required for transport (ESCRT)-mediated pathway that releases vesicles into the extracellular matrix following fusion of the endosomal multivesicular body to the plasma membrane. Initially thought to be a waste disposal system for the cell, exosomes are now reco...
Introduction: Anthracyclines are effective chemotherapeutic agents associated with cardiac toxicity. Anthracycline induced cardiomyopathy (AIC) carries a mortality of 20% at four years. Effective therapies for AIC have not been established. The NIH-sponsored Stem Cell Injection for Cancer Survivors (SENECA) Trial examined the role of allogeneic mes...
Advances in medical robots promise to improve modern medicine and the quality of life. Miniaturization of these robotic platforms has led to numerous applications that leverages precision medicine. In this review, the current trends of medical micro and nanorobotics for therapy, surgery, diagnosis, and medical imaging are discussed. The use of micr...
RAS genes are the most frequently mutated oncogenes in cancer. However, the effects of oncogenic RAS signaling on the noncoding transcriptome are unclear. We analyzed the transcriptomes of human airway epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We found that oncogenic KRAS upregulates non...
Micro/nanorobotics holds considerable promise for advancing diagnosis and treatment of disease. These tiny robotic surgeons could give us access to remote and hard to reach sections of the body and perform diverse medical procedures. In article number 2002203, Fernando Soto, Utkan Demirci, and co‐workers discuss the current trends of medical micro...
We studied the paracrine function of mesenchymal stem cells (MSCs) derived from various sources in response to pulsed focused ultrasound (pFUS). Human adipose tissue (AD), bone marrow (BM), and umbilical cord (UC) derived MSCs were exposed to pFUS at two intensities: 0.45 W/cm2 ISATA (310 kPa PNP) and 1.3 W/cm2 ISATA (540 kPa PNP). Following pFUS,...
Background:
The aim of this study was to examine the effect of a three-step approach that utilizes the application of adipose tissue-derived mesenchymal stem cells (AD-MSCs), encapsulation, and pulsed focused ultrasound (pFUS) to help the engraftment and function of transplanted islets.
Methods:
In step 1, islets were co-cultured with AD-MSCs to...
Plasmonic sensors provide real-time and label-free detection of biotargets with unprecedented sensitivity and detection limit. However, they usually lack the ability to estimate the thickness of the target layer formed on top of the sensing surface. Here, we report a sensing modality based on reflection spectroscopy of a nanoplasmonic Fabry-Perot c...
Magnetic levitational bioassembly of three-dimensional (3D) tissue constructs represents a rapidly emerging scaffold- and label-free approach and alternative conceptual advance in tissue engineering. The magnetic bioassembler has been designed, developed, and certified for life space research. To the best of our knowledge, 3D tissue constructs have...
In article number 1900300, Naside Gözde Durmus, Sean M. Wu, Utkan Demirci, and co‐workers show that magnetic levitation defines the fine balance of living cells where fatty and healthy populations of iPS‐derived cardiomyocytes levitate to a precise height under the magnetic field inside a microfluidic setup engineered as meticulously as the geometr...
Metasurfaces are engineered nanostructured interfaces that extend photonic behavior
of natural materials, and they spurred many breakthroughs in multiple fields, including
quantum optics, optoelectronics and biosensing. Recent advances in metasurface
nanofabrication enable precise manipulation of light–matter interactions at
subwavelength scales. H...
Metasurface fabrication techniques are costly and time consuming since they require multiple complex deposition and patterning steps to build devices with only a small active area. Digital versatile disks (DVDs) are commonly available and are used to play movies. In article number 1907160, Fatih Inci, Utkan Demirci, and co‐workers utilize these DVD...
Rapid and efficient processing of sexual assault evidence to accelerate forensic investigation and decrease casework backlogs is urgently needed. Therefore, the standardized protocols currently used in forensic laboratories can benefit from continued innovation to handle the increasing number and complexity of samples being submitted to forensic la...
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Although bioartificial liver support system (BLSS) plays an essential role in maintaining partial liver functions and detoxification for liver failure patients, hepatocytes are unanimously seeded in biomaterials, which lack the hierarchal structures and mechanical cues of native liver tissues. To address this challenge, we developed a new BLSS by c...
Density is a core material property and varies between different cell types, mainly based on differences in their lipid content. Sorting based on density enables various biomedical applications such as multi‐omics in precision medicine and regenerative repair in medicine. However, a significant challenge is sorting cells of the same type based on d...
How to pack materials into well-defined volumes efficiently has been a longstanding question of interest to physicists, material scientists, and mathematicians as these materials have broad applications ranging from shipping goods in commerce to seeds in agriculture and to spheroids in tissue engineering. How many marbles or gumball candies can you...
A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal an...
The calcium phosphate particles can be used as building blocks for fabrication of 3D scaffolds intended for bone tissue engineering. This work presents for the first time a rapid creation of 3D scaffolds using magnetic levitation of calcium phosphate particles. Namely, tricalcium phosphate particles of equal size and certain porosity are used, whic...
One major challenge for current brain research is generating an integrative understanding of brain’s functions and disorders derived from its multiscale neuronal architectures and connectivity. Thus, innovative neurotechnologies tools are urgently required for deciphering multiscale functional and structural organizations of brain at the hierarchic...
In article number 1905713, Utkan Demirci and co‐workers report a locomotion strategy to guide the formation and operation of multiple nueronal mini‐robots by way of a common acoustic stimulus. These scaffold‐free, ring‐shaped cellu‐robots comprise only highly packed cells, making them less cumbersome during locomotion, and they can react together i...