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A Strong Foundation
Decades of scientific research provide a strong foundation for our technology. Collaborating with researchers from around the globe, our lead scientists Dr. Amir Nezhad (Scholar Profile) and Dr. Razieh Salahandish (Scholar Profile) have published in world-leading academic journals.
Featured Articles
A compact, low-cost, and binary sensing (BiSense) platform for noise-free and self-validated impedimetric detection of COVID-19 infected patients
Electrochemical immuno-biosensors are one of the most promising approaches for accurate, rapid, and quantitative detection of protein biomarkers. The two-working electrode strip is employed for creating a self-supporting system, as a tool for self-validating the acquired results for added reliability. However, the realization of multiplex electrochemical point-of-care testing (ME-POCT) requires advancement in portable, rapid reading, easy-to-use, and low-cost multichannel potentiostat readers. The combined multiplex biosensor strips and multichannel readers allow for suppressing the possible complex matrix effect or ultra-sensitive detection of different protein biomarkers. Herein, a handheld binary-sensing (BiSense) bi-potentiostat was developed to perform electrochemical impedance spectroscopy (EIS)-based signal acquisition from a custom-designed dual-working-electrode immuno-biosensor. BiSense employs a commercially available microcontroller and out-of-shelf components, offering the cheapest yet accurate and reliable time-domain impedance analyzer. A specific electrical board design was developed and customized for impedance signal analysis of SARS-CoV-2 nucleocapsid (N)-protein biosensor in spiked samples and alpha variant clinical nasopharyngeal (NP) swab samples. BiSense showed limit-of-detection (LoD) down to 56 fg/mL for working electrode 1 (WE1) and 68 fg/mL for WE2 and reported with a dynamic detection range of 1 pg/mL to 10 ng/mL for detection of N-protein in spiked samples. The dual biosensing of N-protein in this work was used as a self-validation of the biosensor. The low-cost (∼USD$40) BiSense bi-potentiostat combined with the immuno-biosensors successfully detected COVID-19 infected patients in less than 10 min, with the BiSense reading period shorter than 1.5 min, demonstrating its potential for the realization of ME-POCTs for rapid and hand-held diagnosis of infections.
Immuno-affinity Potent Strip with Pre-Embedded Intermixed PEDOT:PSS Conductive Polymers and Graphene Nanosheets for Bio-Ready Electrochemical Biosensing of Central Nervous System Injury Biomarkers
Future point-of-care (PoC) and wearable electrochemical biosensors explore new technology solutions to eliminate the need for multistep electrode modification and functionalization, overcome the limited reproducibility, and automate the sensing steps. In this work, a new screen-printed immuno-biosensor strip is engineered and characterized using a hybrid graphene nanosheet intermixed with the conductive poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) polymers, all embedded within the base carbon matrix (GiPEC) of the screen-printing ink. This intermixed nanocomposite ink is chemically designed for self-containing the “carboxyl” functional groups as the most specific chemical moiety for protein immobilization on the electrodes. The GiPEC ink enables capturing the target antibodies on the electrode without any need for extra surface preparation. As a proof of concept, the performance of the non-functionalized ready-to-immobilize strips was assessed for the detection of glial fibrillary acidic protein (GFAP) as a known central nervous system injury blood biomarker. This immuno-biosensor exhibits the limit of detection of 281.7 fg mL–1 (3 signal-to-noise ratio) and the sensitivity of 322.6 Ω mL pg–1 mm–2 within the clinically relevant linear detection range from 1 pg mL–1 to 10 ng mL–1. To showcase its potential PoC application, the bio-ready strip is embedded inside a capillary microfluidic device and automates electrochemical quantification of GFAP spiked in phosphate-buffered saline and the human serum. This new electrochemical biosensing platform can be further adapted for the detection of various protein biomarkers with the application in realizing on-chip immunoassays.
A Low-Cost Handheld Impedimetric Biosensing System for Rapid Diagnostics of SARS-CoV-2 Infections
Current laboratory diagnostic approaches for virus detection give reliable results, but they require a lengthy procedure, trained personnel, and expensive equipment and reagents; hence, they are not a suitable choice for home monitoring purposes. This paper addresses this challenge by developing a portable impedimetric biosensing system for the identification of COVID-19 patients. This sensing system has two main parts: a throwaway two-working electrode (2-WE) strip and a novel read-out circuit, specifically designed for simultaneous signal acquisition from both working electrodes. Highly reliable electrochemical signal tracking from multiplex immunosensors provides a potential for flexible and portable multi-biomarker detection. The electrodes’ surfaces were functionalized with SARS-CoV-2 Nucleocapsid Antibody enabling the selective detection of Nucleocapsid protein (N-protein) along with self-validation in the clinical nasopharyngeal swab specimens. The proposed programmable highly sensitive impedance read-out system allows for a wide dynamic detection range, which makes the sensor capable of detecting N-protein concentrations between 0.116 and 10,000 pg/mL. This lightweight and economical read-out arrangement is an ideal prospect for being mass-produced, especially during urgent pandemic situations. Also, such an impedimetric sensing platform has the potential to be redesigned for targeting not only other infectious diseases but also other critical disorders.
Autonomous electrochemical biosensing of glial fibrillary acidic protein for point-of-care detection of central nervous system injuries
The integration of electrochemical biosensors into fluid handling units such as paper-based, centrifugal, and capillary microfluidic devices has been explored with the purpose of developing point-of-care platforms for quantitative detection of bodily fluid markers. However, the present fluidic device designs largely lack the capacity of full assay automation, needing manual loading of one or multiple reagents or requiring external devices for liquid manipulation. Such fluidic handing platforms also require universality for detecting various biomarkers. These platforms are also largely produced using materials unsuitable for scalable manufacturing and with a high production cost. The mechanism of fluid flow also often induces noise to the embedded biosensors which adversely impacts the accuracy of biosensing. This work addresses these challenges by presenting a reliable design of a fully automated and universal capillary-driven microfluidic platform that automates several steps of label-free electrochemical biosensing assays. These steps include sample aliquoting, controlled incubation, removal of non-specific bindings, reagent mixing and delivery to sensing electrodes, and electrochemical detection. The multilayer architecture of the microfluidic device is made of polymeric and adhesive materials commercially used for the fabrication of point-of-care devices. The design and geometry of different components of the device (e.g., sampling unit, mixer, resistances, delay valves, interconnecting components) were optimized using a combined experimental testing and numerical fluid flow modeling to reach high reproducibility and minimize the noise-induced to the biosensor. As a proof of concept, the performance of this on-chip immunosensing platform was demonstrated for rapid and autonomous detection of glial fibrillary acidic proteins (GFAP) in phosphate-buffered saline (PBS). The microfluidic immunosensing device exhibited a linear detection range of 10–1000 pg mL−1 for the detection of GFAP within 30 min, with a limit of detection (LoD) and sensitivity of 3 pg mL−1 and 39 mL pg−1 mm−2 in PBS, respectively. Owing to its simplicity, sample-to-result performance, universality for handing different biofluids, low cost, high reproducibility, compatibility with scalable production, and short analysis time, the proposed biosensing platform can be further adapted for the detection of other biomarkers in different clinical bodily fluids for rapid diagnostic and prognostic applications.
Highly Stable Buffer-Based Zinc Oxide/Reduced Graphene Oxide Nanosurface Chemistry for Rapid Immunosensing of SARS-CoV-2 Antigens
The widespread and long-lasting effect of the COVID-19 pandemic has called attention to the significance of technological advances in the rapid diagnosis of SARS-CoV-2 virus. This study reports the use of a highly stable buffer-based zinc oxide/reduced graphene oxide (bbZnO/rGO) nanocomposite coated on carbon screen-printed electrodes for electrochemical immuno-biosensing of SARS-CoV-2 nuelocapsid (N-) protein antigens in spiked and clinical samples. The incorporation of a salt-based (ionic) matrix for uniform dispersion of the nanomixture eliminates multistep nanomaterial synthesis on the surface of the electrode and enables a stable single-step sensor nanocoating. The immuno-biosensor provides a limit of detection of 21 fg/mL over a linear range of 1–10 000 pg/mL and exhibits a sensitivity of 32.07 ohms·mL/pg·mm2 for detection of N-protein in spiked samples. The N-protein biosensor is successful in discriminating positive and negative clinical samples within 15 min, demonstrating its proof of concept used as a COVID-19 rapid antigen test.
Bi-ECDAQ: An electrochemical dual-immuno-biosensor accompanied by a customized bi-potentiostat for clinical detection of SARS-CoV-2 Nucleocapsid proteins
Multiplex electrochemical biosensors have been used for eliminating the matrix effect in complex bodily fluids or enabling the detection of two or more bioanalytes, overall resulting in more sensitive assays and accurate diagnostics. Many electrochemical biosensors lack reliable and low-cost multiplexing to meet the requirements of point-of-care detection due to either limited functional biosensors for multi-electrode detection or incompatible readout systems. We developed a new dual electrochemical biosensing unit accompanied by a customized potentiostat to address the unmet need for point-of-care multi-electrode electrochemical biosensing. The two-working electrode system was developed using screen-printing of a carboxyl-rich nanomaterial containing ink, with both working electrodes offering active sites for recognition of bioanalytes. The low-cost bi-potentiostat system (∼$80) was developed and customized specifically to the bi-electrode design and used for rapid, repeatable, and accurate measurement of electrochemical impedance spectroscopy signals from the dual biosensor. This binary electrochemical data acquisition (Bi-ECDAQ) system accurately and selectively detected SARS-CoV-2 Nucleocapsid protein (N-protein) in both spiked samples and clinical nasopharyngeal swab samples of COVID-19 patients within 30 min. The two working electrodes offered the limit of detection of 116 fg/mL and 150 fg/mL, respectively, with the dynamic detection range of 1–10,000 pg/mL and the sensitivity range of 2744–2936 Ω mL/pg.mm2 for the detection of N-protein. The potentiostat performed comparable or better than commercial Autolab potentiostats while it is significantly lower cost. The open-source Bi-ECDAQ presents a customizable and flexible approach towards addressing the need for rapid and accurate point-of-care electrochemical biosensors for the rapid detection of various diseases.
Immuno-biosensor on a chip: a self-powered microfluidic-based electrochemical biosensing platform for point-of-care quantification of proteins
The realization of true point-of-care (PoC) systems profoundly relies on integrating the bioanalytical assays into “on-chip” fluid handing platforms, with autonomous performance, reproducible functionality, and capacity in scalable production. Specifically for electrochemical immuno-biosensing, the complexity of the procedure used for ultrasensitive protein detection using screen-printed biosensors necessitates a lab-centralized practice, hindering the path towards near-patient use. This work develops a self-powered microfluidic chip that automates the entire assay of electrochemical immuno-biosensing, enabling controlled and sequential delivery of the biofluid sample and the sensing reagents to the surface of the embedded electrochemical biosensor. Without any need for active fluid handling, this novel sample-to-result testing kit offers antibody–antigen immunoreaction within 15 min followed by the subsequent automatic washing, redox probe delivery, and electrochemical signal recording. The redox molecules ([Fe(CN)6]3−/4−) are pre-soaked and dried in fiber and embedded inside the chip. The dimensions of the fluidic design and the parameters of the electrochemical bioassay are optimized to warrant a consistent and reproducible performance of the autonomous sensing device. The uniform diffusion of the dried redox into the injected solution and its controlled delivery onto the biosensor are modeled via a two-phase flow computational fluid dynamics simulation, determining the suitable time for electrochemical signal measurement from the biosensor. The microfluidic chip performs well with both water-based fluids and human plasma with the optimized sample volume to offer a proof-of-concept ultrasensitive biosensing of SARS-CoV-2 nucleocapsid proteins spiked in phosphate buffer saline within 15 min. The on-chip N-protein biosensing demonstrates a linear detection range of 10 to 1000 pg mL−1 with a limit of detection of 3.1 pg mL−1. This is the first self-powered microfluidic-integrated electrochemical immuno-biosensor that promises quantitative and ultrasensitive PoC biosensing. Once it is modified for its design and dimensions, it can be further used for autonomous detection of one or multiple proteins in diverse biofluid samples.
Bibliography
Ayala-Charca, G., R. Salahandish, M. Khalghollah, D. Sadighbayan, F. Haghayegh, A. Sanati-Nezhad and E. Ghafar-Zadeh (2022). "A Low-Cost Handheld Impedimetric Biosensing System for Rapid Diagnostics of SARS-CoV-2 Infections." IEEE Sensors Journal 22(16): 15673-15682.
Haghayegh, F., R. Salahandish, A. Zare, M. Khalghollah and A. Sanati-Nezhad (2022). "Immuno-biosensor on a chip: a self-powered microfluidic-based electrochemical biosensing platform for point-of-care quantification of proteins." Lab on a Chip 22(1): 108-120.
Salahandish, R., F. Haghayegh, G. Ayala-Charca, J. E. Hyun, M. Khalghollah, A. Zare, B. Far, B. M. Berenger, Y. D. Niu, E. Ghafar-Zadeh and A. Sanati-Nezhad (2022). "Bi-ECDAQ: An electrochemical dual-immuno-biosensor accompanied by a customized bi-potentiostat for clinical detection of SARS-CoV-2 Nucleocapsid proteins." Biosensors and Bioelectronics 203: 114018.
Salahandish, R., F. Haghayegh, S. Khetani, M. Hassani and A. S. Nezhad (2022). "Immuno-affinity Potent Strip with Pre-Embedded Intermixed PEDOT:PSS Conductive Polymers and Graphene Nanosheets for Bio-Ready Electrochemical Biosensing of Central Nervous System Injury Biomarkers." ACS Applied Materials & Interfaces 14(25): 28651-28662.
Salahandish, R., M. Hassani, A. Zare, F. Haghayegh and A. Sanati-Nezhad (2022). "Autonomous electrochemical biosensing of glial fibrillary acidic protein for point-of-care detection of central nervous system injuries." Lab on a Chip 22(8): 1542-1555.
Salahandish, R., P. Jalali, H. O. Tabrizi, J. E. Hyun, F. Haghayegh, M. Khalghollah, A. Zare, B. M. Berenger, Y. D. Niu, E. Ghafar-Zadeh and A. Sanati-Nezhad (2022). "A compact, low-cost, and binary sensing (BiSense) platform for noise-free and self-validated impedimetric detection of COVID-19 infected patients." Biosensors and Bioelectronics 213: 114459.
Hassanpour Tamrin, S., A. Sanati Nezhad and A. Sen (2021). "Label-Free Isolation of Exosomes Using Microfluidic Technologies." ACS Nano 15(11): 17047-17079.
Mohammadi, M., H. Zargartalebi, R. Salahandish, R. Aburashed, K. Wey Yong and A. Sanati-Nezhad (2021). "Emerging technologies and commercial products in exosome-based cancer diagnosis and prognosis." Biosensors and Bioelectronics 183: 113176.
Ale Ebrahim, S., A. Ashtari, M. Zamani Pedram, N. Ale Ebrahim and A. Sanati-Nezhad (2020). "Publication Trends in Exosomes Nanoparticles for Cancer Detection." Int J Nanomedicine 15: 4453-4470.
Salahandish, R., A. Ghaffarinejad, S. M. Naghib, A. Niyazi, K. Majidzadeh-A, M. Janmaleki and A. Sanati-Nezhad (2019). "Sandwich-structured nanoparticles-grafted functionalized graphene based 3D nanocomposites for high-performance biosensors to detect ascorbic acid biomolecule." Scientific Reports 9(1): 1226.
Salahandish, R., A. Ghaffarinejad, S. M. Naghib, K. Majidzadeh-A and A. Sanati-Nezhad (2018). "A Novel Graphene-Grafted Gold Nanoparticles Composite for Highly Sensitive Electrochemical Biosensing." IEEE Sensors Journal 18(6): 2513-2519.
Salahandish, R., A. Ghaffarinejad, S. M. Naghib, K. Majidzadeh-A, H. Zargartalebi and A. Sanati-Nezhad (2018). "Nano-biosensor for highly sensitive detection of HER2 positive breast cancer." Biosensors and Bioelectronics 117: 104-111.
Salahandish, R., A. Ghaffarinejad, E. Omidinia, H. Zargartalebi, K. Majidzadeh-A, S. M. Naghib and A. Sanati-Nezhad (2018). "Label-free ultrasensitive detection of breast cancer miRNA-21 biomarker employing electrochemical nano-genosensor based on sandwiched AgNPs in PANI and N-doped graphene." Biosensors and Bioelectronics 120: 129-136.
Gholizadeh, S., M. Shehata Draz, M. Zarghooni, A. Sanati-Nezhad, S. Ghavami, H. Shafiee and M. Akbari (2017). "Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: Current status and future directions." Biosensors and Bioelectronics 91: 588-605.
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