All Publications


  • High spatial and temporal resolution using upconversion nanoparticles and femtosecond pulsed laser in single particle tracking CURRENT APPLIED PHYSICS Lee, J., Lee, H., Kang, M., Baday, M., Lee, S. 2022; 44: 40-45
  • TNTdetect.AI: A Deep Learning Model for Automated Detection and Counting of Tunneling Nanotubes in Microscopy Images. Cancers Ceran, Y., Erguder, H., Ladner, K., Korenfeld, S., Deniz, K., Padmanabhan, S., Wong, P., Baday, M., Pengo, T., Lou, E., Patel, C. B. 2022; 14 (19)

    Abstract

    BACKGROUND: Tunneling nanotubes (TNTs) are cellular structures connecting cell membranes and mediating intercellular communication. TNTs are manually identified and counted by a trained investigator; however, this process is time-intensive. We therefore sought to develop an automated approach for quantitative analysis of TNTs.METHODS: We used a convolutional neural network (U-Net) deep learning model to segment phase contrast microscopy images of both cancer and non-cancer cells. Our method was composed of preprocessing and model development. We developed a new preprocessing method to label TNTs on a pixel-wise basis. Two sequential models were employed to detect TNTs. First, we identified the regions of images with TNTs by implementing a classification algorithm. Second, we fed parts of the image classified as TNT-containing into a modified U-Net model to estimate TNTs on a pixel-wise basis.RESULTS: The algorithm detected 49.9% of human expert-identified TNTs, counted TNTs, and calculated the number of TNTs per cell, or TNT-to-cell ratio (TCR); it detected TNTs that were not originally detected by the experts. The model had 0.41 precision, 0.26 recall, and 0.32 f-1 score on a test dataset. The predicted and true TCRs were not significantly different across the training and test datasets (p = 0.78).CONCLUSIONS: Our automated approach labeled and detected TNTs and cells imaged in culture, resulting in comparable TCRs to those determined by human experts. Future studies will aim to improve on the accuracy, precision, and recall of the algorithm.

    View details for DOI 10.3390/cancers14194958

    View details for PubMedID 36230881

  • Biomimetic Hydrogels in the Study of Cancer Mechanobiology: Overview, Biomedical Applications, and Future Perspectives. Gels (Basel, Switzerland) Sahan, A. Z., Baday, M., Patel, C. B. 2022; 8 (8)

    Abstract

    Hydrogels are biocompatible polymers that are tunable to the system under study, allowing them to be widely used in medicine, bioprinting, tissue engineering, and biomechanics. Hydrogels are used to mimic the three-dimensional microenvironment of tissues, which is essential to understanding cell-cell interactions and intracellular signaling pathways (e.g., proliferation, apoptosis, growth, and survival). Emerging evidence suggests that the malignant properties of cancer cells depend on mechanical cues that arise from changes in their microenvironment. These mechanobiological cues include stiffness, shear stress, and pressure, and have an impact on cancer proliferation and invasion. The hydrogels can be tuned to simulate these mechanobiological tissue properties. Although interest in and research on the biomedical applications of hydrogels has increased in the past 25 years, there is still much to learn about the development of biomimetic hydrogels and their potential applications in biomedical and clinical settings. This review highlights the application of hydrogels in developing pre-clinical cancer models and their potential for translation to human disease with a focus on reviewing the utility of such models in studying glioblastoma progression.

    View details for DOI 10.3390/gels8080496

    View details for PubMedID 36005097

  • SARcopenia Assessment in Hypertension: The SARAH Study. American journal of physical medicine & rehabilitation Kara, M., Kara, O., Ceran, Y., Kaymak, B., Kaya, T. C., Citir, B. N., Durmus, M. E., Durmusoglu, E., Razaq, S., Dogan, Y., Shehab, D., Alkandari, S. A., Abdulsalam, A. J., Ata, A. M., Koyuncu, E. G., Coskun, E., Turan, G., Dilek, B., Culha, M. A., Yildirim, P., Mezian, K., Dogu, B., Kilic, G., Unlu, Z., Barbosa, J., Pinho, S., Analay, P., Palamar, D., Guvener, O., Ocak, H., Malas, F. U., Baday, M., Cakir, B., Ozcakar, L. 2022

    Abstract

    OBJECTIVE: To investigate the relationship between sarcopenia and RAS-related disorders and to explore the effects of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) on muscle mass/function and physical performance.DESIGN: This multi-center, cross-sectional study was performed using ISarcoPRM algorithm for the diagnosis of sarcopenia.RESULTS: Of the 2613 participants (mean age; 61.0 ± 9.5 years), 1775 (67.9%) were hypertensive. All sarcopenia-related parameters [except chair stand test (CST) in males] were worse in hypertensive group than in normotensive group (all p < 0.05). When clinical/potential confounders were adjusted; HT was found to be an independent predictor of sarcopenia in males [OR = 2.403 (95%CI: 1.514-3.813)] and females [OR = 1.906 (95%CI: 1.328-2.734)] (both p < 0.001). After adjusting for confounding factors, we found that all sarcopenia-related parameters (except grip strength and CST in males) were independently/negatively related with HT (all p < 0.05). In females, ACEIs users had higher grip strength and CST performance values but had lower muscle thickness and gait speed values, as compared to those using ARBs (all p < 0.05).CONCLUSIONS: Hypertension was associated with increased risk of sarcopenia at least two times. Among antihypertensives; while ACEIs had higher muscle values, ARBs had higher muscle mass and physical performance values only in females.

    View details for DOI 10.1097/PHM.0000000000002045

    View details for PubMedID 35550378

  • Electrophysiological Characterization of Glioma using a Biomimetic Spheroid Model Kim, K., Tercan, S., Baday, M., Mahaney, K. B., Recht, L. D., Rajadas, J., Patel, C. B., IEEE IEEE. 2021: 86-89
  • Isolation, Detection, and Quantification of Cancer Biomarkers in HPV-Associated Malignancies. Scientific reports Inan, H., Wang, S., Inci, F., Baday, M., Zangar, R., Kesiraju, S., Anderson, K. S., Cunningham, B. T., Demirci, U. 2017; 7 (1): 3322

    Abstract

    Human Papillomavirus (HPV) infection has been recognized as the main etiologic factor in the development of various cancers including penile, vulva, oropharyngeal and cervical cancers. In the development of cancer, persistent HPV infections induce E6 and E7 oncoproteins, which promote cell proliferation and carcinogenesis resulting elevated levels of host antibodies (e.g., anti-HPV16 E7 antibody). Currently, these cancers are clinically diagnosed using invasive biopsy-based tests, which are performed only in centralized labs by experienced clinical staff using time-consuming and expensive tools and technologies. Therefore, these obstacles constrain their utilization at primary care clinics and in remote settings, where resources are limited. Here, we present a rapid, inexpensive, reliable, easy-to-use, customized immunoassay platform following a microfluidic filter device to detect and quantify anti-HPV16 E7 antibodies from whole blood as a non-invasive assisting technology for diagnosis of HPV-associated malignancies, especially, at primary healthcare and remote settings. The platform can detect and quantify anti-HPV16 E7 antibody down to 2.87 ng/mL. We further validated our immunoassay in clinical patient samples and it provided significantly high responses as compared to control samples. Thus, it can be potentially implemented as a pretesting tool to identify high-risk groups for broad monitoring of HPV-associated cancers in resource-constrained settings.

    View details for DOI 10.1038/s41598-017-02672-6

    View details for PubMedID 28607383

    View details for PubMedCentralID PMC5468352

  • Photonic crystals: emerging biosensors and their promise for point-of-care applications. Chemical Society reviews Inan, H., Poyraz, M., Inci, F., Lifson, M. A., Baday, M., Cunningham, B. T., Demirci, U. 2017; 46 (2): 366-388

    Abstract

    Biosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.

    View details for DOI 10.1039/c6cs00206d

    View details for PubMedID 27841420

  • Probing the Heterogeneity of Protein Kinase Activation in Cells by Super-resolution Microscopy ACS NANO Zhang, R., Fruhwirth, G. O., Coban, O., Barrett, J. E., Burgoyne, T., Lee, S. H., Simonson, P. D., Baday, M., Kholodenko, B. N., Futter, C. E., Ng, T., Selvin, P. R. 2017; 11 (1): 249-257

    Abstract

    Heterogeneity of mitogen-activated protein kinase (MAPK) activation in genetically identical cells, which occurs in response to epidermal growth factor receptor (EGFR) signaling, remains poorly understood. MAPK cascades integrate signals emanating from different EGFR spatial locations, including the plasma membrane and endocytic compartment. We previously hypothesized that in EGF-stimulated cells the MAPK phosphorylation (pMAPK) level and activity are largely determined by the spatial organization of the EGFR clusters within the cell. For experimental testing of this hypothesis, we used super-resolution microscopy to define EGFR clusters by receptor numbers (N) and average intracluster distances (d). From these data, we predicted the extent of pMAPK with 85% accuracy on a cell-to-cell basis with control data returning 54% accuracy (P < 0.001). For comparison, the prediction accuracy was only 61% (P = 0.382) when the diffraction-limited averaged fluorescence intensity/cluster was used. Large clusters (N ≥ 3) with d > 50 nm were most predictive for pMAPK level in cells. Electron microscopy revealed that these large clusters were primarily localized to the limiting membrane of multivesicular bodies (MVB). Many tighter packed dimers/multimers (d < 50 nm) were found on intraluminal vesicles within MVBs, where they were unlikely to activate MAPK because of the physical separation. Our results suggest that cell-to-cell differences in N and d contain crucial information to predict EGFR-activated cellular pMAPK levels and explain pMAPK heterogeneity in isogenic cells.

    View details for DOI 10.1021/acsnano.6b05356

    View details for Web of Science ID 000392886500026

    View details for PubMedCentralID PMC5269639

  • Advances in biosensing strategies for HIV-1 detection, diagnosis, and therapeutic monitoring ADVANCED DRUG DELIVERY REVIEWS Lifson, M. A., Ozen, M. O., Inci, F., Wang, S., Inan, H., Baday, M., Henrich, T. J., Demirci, U. 2016; 103: 90-104

    Abstract

    HIV-1 is a major global epidemic that requires sophisticated clinical management. There have been remarkable efforts to develop new strategies for detecting and treating HIV-1, as it has been challenging to translate them into resource-limited settings. Significant research efforts have been recently devoted to developing point-of-care (POC) diagnostics that can monitor HIV-1 viral load with high sensitivity by leveraging micro- and nano-scale technologies. These POC devices can be applied to monitoring of antiretroviral therapy, during mother-to-child transmission, and identification of latent HIV-1 reservoirs. In this review, we discuss current challenges in HIV-1 diagnosis and therapy in resource-limited settings and present emerging technologies that aim to address these challenges using innovative solutions.

    View details for DOI 10.1016/j.addr.2016.05.018

    View details for Web of Science ID 000380083700007

    View details for PubMedID 27262924

    View details for PubMedCentralID PMC4943868

  • Integrating Cell Phone Imaging with Magnetic Levitation (i-LEV) for Label-Free Blood Analysis at the Point-of-Living. Small Baday, M., Calamak, S., Durmus, N. G., Davis, R. W., Steinmetz, L. M., Demirci, U. 2016; 12 (9): 1222-1229

    Abstract

    There is an emerging need for portable, robust, inexpensive, and easy-to-use disease diagnosis and prognosis monitoring platforms to share health information at the point-of-living, including clinical and home settings. Recent advances in digital health technologies have improved early diagnosis, drug treatment, and personalized medicine. Smartphones with high-resolution cameras and high data processing power enable intriguing biomedical applications when integrated with diagnostic devices. Further, these devices have immense potential to contribute to public health in resource-limited settings where there is a particular need for portable, rapid, label-free, easy-to-use, and affordable biomedical devices to diagnose and continuously monitor patients for precision medicine, especially those suffering from rare diseases, such as sickle cell anemia, thalassemia, and chronic fatigue syndrome. Here, a magnetic levitation-based diagnosis system is presented in which different cell types (i.e., white and red blood cells) are levitated in a magnetic gradient and separated due to their unique densities. Moreover, an easy-to-use, smartphone incorporated levitation system for cell analysis is introduced. Using our portable imaging magnetic levitation (i-LEV) system, it is shown that white and red blood cells can be identified and cell numbers can be quantified without using any labels. In addition, cells levitated in i-LEV can be distinguished at single-cell resolution, potentially enabling diagnosis and monitoring, as well as clinical and research applications.

    View details for DOI 10.1002/smll.201501845

    View details for PubMedID 26523938

    View details for PubMedCentralID PMC4775401

  • Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics. Proceedings of the National Academy of Sciences of the United States of America Inci, F., Filippini, C., Baday, M., Ozen, M. O., Calamak, S., Durmus, N. G., Wang, S., Hanhauser, E., Hobbs, K. S., Juillard, F., Kuang, P. P., Vetter, M. L., Carocci, M., Yamamoto, H. S., Takagi, Y., Yildiz, U. H., Akin, D., Wesemann, D. R., Singhal, A., Yang, P. L., Nibert, M. L., Fichorova, R. N., Lau, D. T., Henrich, T. J., Kaye, K. M., Schachter, S. C., Kuritzkes, D. R., Steinmetz, L. M., Gambhir, S. S., Davis, R. W., Demirci, U. 2015; 112 (32): E4354-63

    Abstract

    Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which addresses all these impediments on a single platform. The NE(2)RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes.

    View details for DOI 10.1073/pnas.1510824112

    View details for PubMedID 26195743

    View details for PubMedCentralID PMC4538635

  • Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device ((NERD)-R-2) for diagnostics PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Inci, F., Filippini, C., Baday, M., Ozen, M. O., Calamak, S., Durmus, N. G., Wang, S., Hanhauser, E., Hobbs, K. S., Juillard, F., Kuang, P. P., Vetter, M. L., Carocci, M., Yamamoto, H. S., Takagi, Y., Yildiz, U. H., Akin, D., Wesemann, D. R., Singhal, A., Yang, P. L., Nibert, M. L., Fichorova, R. N., Lau, D. T., Henrich, T. J., Kaye, K. M., Schachter, S. C., Kuritzkes, D. R., Steinmetz, L. M., Gambhir, S. S., Davis, R. W., Demirci, U. 2015; 112 (32): E4354-E4363

    Abstract

    Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which addresses all these impediments on a single platform. The NE(2)RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes.

    View details for DOI 10.1073/pnas.1510824112

    View details for Web of Science ID 000359285100006

    View details for PubMedID 26195743

    View details for PubMedCentralID PMC4538635