More Like this

1. A label-free and low-power microelectronic impedance spectroscopy for characterization of exosomes

   https://doi.org/10.1371/journal.pone.0270844  

   Shi, Leilei; Esfandiari, Leyla (July 2022, PLOS ONE)

   Khalil, Khalil Abdelrazek (Ed.)

   Electrical Impedance Spectroscopy (EIS) is a non-invasive and label-free technology that can characterize and discriminate cells based on their dielectric properties at a wide range of frequency. This characterization method has not been utilized for small extracellular vesicles (exosomes) with heterogenous and nano-scale size distribution. Here, we developed a novel label-free microelectronic impedance spectroscopy for non-invasive and rapid characterization of exosomes based on their unique dielectric properties. The device is comprised of an insulator-based dielectrophoretic (iDEP) module for exosomes isolation followed by an impedance spectroscopy utilizing the embedded micro-electrodes. This device is capable of distinguishing between exosomes harvested from different cellular origins as the result of their unique membrane and cytosolic compositions at a wide range of frequency. Therefore, it has the potential to be further evolved as a rapid tool for characterization of pathogenic exosomes in clinical settings. 

   more » « less
2. A Label-Free Electrical Impedance Spectroscopy for Detection of Clusters of Extracellular Vesicles Based on Their Unique Dielectric Properties

   https://doi.org/10.3390/bios12020104  

   Zhang, Yuqian; Murakami, Kazutoshi; Borra, Vishnupriya J.; Ozen, Mehmet Ozgun; Demirci, Utkan; Nakamura, Takahisa; Esfandiari, Leyla (February 2022, Biosensors)

   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 study, a novel frequency-dependent impedance measurement system has been developed to characterize EVs based on their unique dielectric properties. The system is composed of an insulator-based dielectrophoretic (iDEP) device to entrap and immobilize a cluster of vesicles followed by utilizing electrical impedance spectroscopy (EIS) to measure their impedance at a wide frequency spectrum, aiming to analyze both their membrane and cytosolic charge-dependent contents. The EIS was initially utilized to detect nano-size vesicles with different biochemical compositions, including liposomes synthesized with different lipid compositions, as well as EVs and lipoproteins with similar biophysical properties but dissimilar biochemical properties. Moreover, EVs derived from the same parental cells but treated with different culture conditions were characterized to investigate the correlation of impedance changes with biochemical properties and functionality in terms of pro-inflammatory responses. The system also showed the ability to discriminate between EVs derived from different cellular origins as well as among size-sorted EVs harbored from the same cellular origin. This proof-of-concept approach is the first step towards utilizing EIS as a label-free, non-invasive, and rapid sensor for detection and characterization of pathogenic EVs and other nanovesicles in the future. 

   more » « less
3. Label-free ferrohydrodynamic separation of exosome-like nanoparticles

   https://doi.org/10.1039/d0lc00609b  

   Liu, Yang; Zhao, Wujun; Cheng, Rui; Logun, Meghan; Zayas-Viera, Maria del; Karumbaiah, Lohitash; Mao, Leidong (August 2020, Lab on a Chip)

   null (Ed.)

   Isolation of exosomes from biological samples provides a minimally-invasive alternative for basic understanding, diagnosis, and prognosis of metastatic cancers. The biology and clinical values of exosomes are under intensive investigation, yet most studies are limited by technical challenges in recovering these exosomes with heterogeneous sizes and cargos from biological samples. We report a novel method based on “particle ferrohydrodynamics” and its associated microfluidic device, termed as the FerroChip, which can separate exosome-like nanoparticles from microliters of cell culture media and human serum in a label-free, continuous-flow and size-dependent manner, and achieves a high recovery rate (94.3%) and a high purity (87.9%). Separated exosome-like nanoparticles had diameters, morphology, and protein expressions that were consistent with other reports. This method, upon further molecular characterization, could potentially facilitate basic understanding of exosomes and its clinical application in blood liquid biopsy. 

   more » « less
4. DESIGN OF A HYBRID-INERTIAL DEVICE FOR THE SEPARATION OF CIRCULATING TUMOR CELLS

   https://doi.org/10.1115/DMD2023-1844  

   Uddin, Mohammed Raihan; Chen, Xiaolin (April 2023, Proceedings of ASME Design of Medical Devices Conference)

   Abstract Circulating tumor cells (CTCs) are shed from primary tumors, circulate in the bloodstream and are capable of initiating metastasis at distant anatomical sites. The detection and molecular characterization of CTCs are pivotal for early-stage cancer diagnosis and prognosis. Recently, microfluidic technology has achieved significant progress in the separation of cells from complex and heterogeneous mixtures for many biomedical applications. Conventional microfluidic platforms exploit the difference in size between the particles to achieve separation, which makes them ineffective for sorting overlapping-sized CTCs. To address this issue, we propose a method using a spiral channel for label-free, and high throughput separation of CTCs coupling Dielectrophoresis (DEP) with inertial microfluidics. A numerical model has been developed to investigate the separation effectiveness of the device over a range of electrical voltage and flow rates. The presented channel is shown to effectively isolate similar-sized CTCs from the white blood cells (WBCs) in a single-stage separation process. Subsequently, optimum working parameters to enhance separation efficiency have been proposed. The hybrid microfluidic device can provide valuable insight into the development of a robust, inexpensive, and efficient platform for cell separation with reduced analysis time for future cancer research and treatment. 

   more » « less
5. Single-Cell Classification Based on Population Nucleus Size Combining Microwave Impedance Spectroscopy and Machine Learning

   https://doi.org/10.3390/s23021001  

   Ferguson, Caroline A.; Hwang, James C.; Zhang, Yu; Cheng, Xuanhong (January 2023, Sensors)

   Many recent efforts in the diagnostic field address the accessibility of cancer diagnosis. Typical histological staining methods identify cancer cells visually by a larger nucleus with more condensed chromatin. Machine learning (ML) has been incorporated into image analysis for improving this process. Recently, impedance spectrometers have been shown to generate all-inclusive lab-on-a-chip platforms to detect nucleus abnormities. In this paper, a wideband electrical sensor and data analysis paradigm that can identify nuclear changes shows the realization of a single-cell microfluidic device to detect nuclei of altered sizes. To model cells of altered nucleus, Jurkat cells were treated to enlarge or shrink their nucleus followed by broadband sensing to obtain the S-parameters of single cells. The ability to deduce important frequencies associated with nucleus size is demonstrated and used to improve classification models in both binary and multiclass scenarios, despite a heterogeneous and overlapping cell population. The important frequency features match those predicted in a double-shell circuit model published in prior work, demonstrating a coherent new analytical technique for electrical data analysis. The electrical sensing platform assisted by ML with impressive accuracy of cell classification looks forward to a label-free and flexible approach to cancer diagnosis. 

   more » « less