Lab on a Chip for High-Throughput Drug Screening

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Optical and Photonic Biosensors".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 27657

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Guest Editor
Center for Cellular and Molecular Diagnostics, School of Medicine, Tulane University, New Orleans, LA 70112, USA
Interests: bioelectronics; micro-electro-mechanical systems (MEMS); chemical sensors; additive printing; biomedical electronics and sensors; micro-nano materials and devices; protein engineering; synthetic biology
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Guest Editor
Department of Mechanical Engineering, University of Houston, Houston, TX 77004, USA
Interests: flexible/stretchable electronics; micro-electro-mechanical systems (MEMS); nano-micro-macro manufacturing; additive printing; biomedical electronics and sensors; micro-nano materials and devices; solid state electronics; energy harvesting and storage
Special Issues, Collections and Topics in MDPI journals
Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
Interests: in vitro diagnosis; clinical chemistry; pathology and clinical testing; flow cytometry; mass spectrometry; lab on a chip; drug testing

Special Issue Information

Dear Colleagues,

The current state of drug-screening methods suffers from increasing costs, a time-consuming nature, and the fact that more than 90% of screened drug candidates fail after entering clinical trials, largely due to the inability to accurately capture human responses in drug screening. Although challenges remain, the development of biosensor technologies and materials offers new opportunities for lab on a chip, which can be adopted in academia and the pharmaceutical industry to benefit drug screening. Importantly, during the drug-screening stage, lab on a chip allows high-throughput testing and flexible automation with miniaturized sizes, low costs, high accuracy and user-friendliness, based on the miniaturization and integration of multiple laboratory functions.

This Special Issue is soliciting original articles and reviews on “Lab on a Chip for High-Throughput Drug Screening”, mainly focusing on novel techniques, the recent advances in this field, and the potential opportunities and challenges for their application. We would like to invite you to submit your manuscript to us. 

Prof. Dr. Chenzhong Li
Dr. Cunjiang Yu
Dr. Shan Liu
Guest Editors

If you want to learn more information or need any advice, you can contact the Special Issue Editor Jessica Zhou via <[email protected]> directly.

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Keywords

  • lab-on-a-chip
  • microfluidics
  • organ-on-a-chip
  • biosensors
  • bioMEMS
  • drug screening
  • drug testing
  • single cell
  • cell/tissue engineering

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Published Papers (8 papers)

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Research

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12 pages, 37095 KiB  
Article
Sensing Bioavailable Water Content of Granulated Matrices: A Combined Experimental and Computational Study
by Ria Ghosh, Neha Bhattacharyya, Amrita Banerjee, Lopamudra Roy, Debdatta Mukherjee, Soumendra Singh, Arpita Chattopadhyay, Tapan Adhikari and Samir Kumar Pal
Biosensors 2023, 13(2), 185; https://doi.org/10.3390/bios13020185 - 25 Jan 2023
Cited by 2 | Viewed by 1590
Abstract
This paper represents the synthesis, characterization and validation of a cobalt chloride functionalised nano-porous cellulose membrane, a unique sensor for non-contact measurement of water potential in various biomedical and environmentally important matrices. The developed nano sensor, along with associated electronic components, is assembled [...] Read more.
This paper represents the synthesis, characterization and validation of a cobalt chloride functionalised nano-porous cellulose membrane, a unique sensor for non-contact measurement of water potential in various biomedical and environmentally important matrices. The developed nano sensor, along with associated electronic components, is assembled as a prototype device called “MEGH” (Measuring Essential Good Hydration) to measure essential hydration of matrices of both environmental and biomedical importance, including soil and human skin. The relative humidity above the soil surface in equilibrium with the soil moisture has been studied for both hydrophobic and hydrophilic soil types. Our studies confirm that the percentage of water available to plants is greater in hydrophobic soil rather than in hydrophilic soil, which has also been corroborated using simulation studies. Furthermore, the requirement of hydration in human skin has also been evaluated by measuring the water potential of both dry and moist skin. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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19 pages, 3247 KiB  
Article
On-Chip Electromembrane Surrounded Solid Phase Microextraction for Determination of Tricyclic Antidepressants from Biological Fluids Using Poly(3,4-ethylenedioxythiophene)—Graphene Oxide Nanocomposite as a Fiber Coating
by Razieh Zamani and Yadollah Yamini
Biosensors 2023, 13(1), 139; https://doi.org/10.3390/bios13010139 - 14 Jan 2023
Cited by 8 | Viewed by 2280
Abstract
In the present study, on-chip electromembrane surrounded solid phase microextraction (EM-SPME) was employed in the determination of tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, desipramine, maprotiline, and sertraline, from various biological fluids. In this regard, poly(3,4-ethylenedioxythiophene)–graphene oxide (PEDOT-GO) was electrodeposited on an SPME [...] Read more.
In the present study, on-chip electromembrane surrounded solid phase microextraction (EM-SPME) was employed in the determination of tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, desipramine, maprotiline, and sertraline, from various biological fluids. In this regard, poly(3,4-ethylenedioxythiophene)–graphene oxide (PEDOT-GO) was electrodeposited on an SPME fiber as a conductive coating, then the fiber played the acceptor-electrode role during the extraction. Thus, the immigration of the analytes under the influence of an electric field and their absorption onto the fiber coating were accomplished simultaneously. Under the optimized conditions, the limits of detection for the target analytes were acquired in the range of 0.005–0.025 µg L−1 using gas chromatography–mass spectrometry. The linearity of the method was 0.010–500 µg L−1 for the imipramine and sertraline, 0.025–500 µg L−1 for the amitriptyline, nortriptyline, and desipramine, and 1.000–250 µg L−1 for the maprotiline (R2 ≥ 0.9984). Moreover, this method provided suitable precision and fiber-to-fiber reproducibility, with RSDs ≤ 8.4%. The applicability of the proposed setup was eventually investigated for extraction of the drugs from human bone marrow aspirate, urine, plasma, and well water samples, in which satisfactory relative recoveries, from 93–105%, were obtained. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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18 pages, 4311 KiB  
Article
Electric Cell-Substrate Impedance Sensing (ECIS) as a Platform for Evaluating Barrier-Function Susceptibility and Damage from Pulmonary Atelectrauma
by Eiichiro Yamaguchi, Joshua Yao, Allison Aymond, Douglas B. Chrisey, Gary F. Nieman, Jason H. T. Bates and Donald P. Gaver
Biosensors 2022, 12(6), 390; https://doi.org/10.3390/bios12060390 - 5 Jun 2022
Cited by 9 | Viewed by 2990
Abstract
Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells [...] Read more.
Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441. Atelectrauma was mimicked through recruitment/derecruitment (RD) of a semi-infinite air bubble to the fluid-occluded micro-channel. We show that a confluent monolayer with a high level of barrier function is nearly impervious to atelectrauma for hundreds of RD events. Nevertheless, barrier function is eventually diminished, and after a critical number of RD insults, the monolayer disintegrates exponentially. Confluent layers with lower initial barrier function are less resilient. These results indicate that the first line of defense from atelectrauma resides with intercellular binding. After disruption, the epithelial layer community protection is diminished and atelectrauma ensues. ECIS may provide a platform for identifying damaging stimuli, ventilation scenarios, or pharmaceuticals that can reduce susceptibility or enhance barrier-function recovery. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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15 pages, 743 KiB  
Article
Longitudinal Study of Circulating Biomarkers in Patients with Resectable Pancreatic Ductal Adenocarcinoma
by Pablo J. Dopico, Minh-Chau N. Le, Benjamin Burgess, Zhijie Yang, Yu Zhao, Youxiang Wang, Thomas J. George and Z. Hugh Fan
Biosensors 2022, 12(4), 206; https://doi.org/10.3390/bios12040206 - 30 Mar 2022
Cited by 7 | Viewed by 2893
Abstract
While patients with resectable pancreatic ductal adenocarcinoma (PDAC) show improved survival compared to their non-resectable counterparts, survival remains low owing to occult metastatic disease and treatment resistance. Liquid biopsy based on circulating tumor cells (CTCs) and cell-free DNA (cfDNA) has been shown to [...] Read more.
While patients with resectable pancreatic ductal adenocarcinoma (PDAC) show improved survival compared to their non-resectable counterparts, survival remains low owing to occult metastatic disease and treatment resistance. Liquid biopsy based on circulating tumor cells (CTCs) and cell-free DNA (cfDNA) has been shown to predict recurrence and treatment resistance in various types of cancers, but their utility has not been fully demonstrated in resectable PDAC. We have simultaneously tracked three circulating biomarkers, including CTCs, cfDNA, and circulating tumor DNA (ctDNA), over a period of cancer treatment using a microfluidic device and droplet digital PCR (ddPCR). The microfluidic device is based on the combination of filtration and immunoaffinity mechanisms. We have measured CTCs, cfDNA, and ctDNA in a cohort of seven resectable PDAC patients undergoing neoadjuvant therapy followed by surgery, and each patient was followed up to 10 time points over a period of 4 months. CTCs were detectable in all patients (100%) at some point during treatment but were detectable in only three out of six patients (50%) prior to the start of treatment. Median cfDNA concentrations remained comparable to negative controls throughout treatment. ddPCR was able to find KRAS mutations in six of seven patients (86%); however, these mutations were present in only two of seven patients (29%) prior to treatment. Overall, the majority of circulating biomarkers (81% for CTCs and 91% for cfDNA/ctDNA) were detected after the start of neoadjuvant therapy but before surgery. This study suggests that a longitudinal study of circulating biomarkers throughout treatment provides more useful information than those single time-point tests for resectable PDAC patients. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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Review

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25 pages, 6096 KiB  
Review
The Synergy between Deep Learning and Organs-on-Chips for High-Throughput Drug Screening: A Review
by Manna Dai, Gao Xiao, Ming Shao and Yu Shrike Zhang
Biosensors 2023, 13(3), 389; https://doi.org/10.3390/bios13030389 - 15 Mar 2023
Cited by 8 | Viewed by 5015
Abstract
Organs-on-chips (OoCs) are miniature microfluidic systems that have arguably become a class of advanced in vitro models. Deep learning, as an emerging topic in machine learning, has the ability to extract a hidden statistical relationship from the input data. Recently, these two areas [...] Read more.
Organs-on-chips (OoCs) are miniature microfluidic systems that have arguably become a class of advanced in vitro models. Deep learning, as an emerging topic in machine learning, has the ability to extract a hidden statistical relationship from the input data. Recently, these two areas have become integrated to achieve synergy for accelerating drug screening. This review provides a brief description of the basic concepts of deep learning used in OoCs and exemplifies the successful use cases for different types of OoCs. These microfluidic chips are of potential to be assembled as highly potent human-on-chips with complex physiological or pathological functions. Finally, we discuss the future supply with perspectives and potential challenges in terms of combining OoCs and deep learning for image processing and automation designs. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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32 pages, 3060 KiB  
Review
In Vitro Tumor Models on Chip and Integrated Microphysiological Analysis Platform (MAP) for Life Sciences and High-Throughput Drug Screening
by Huyen Ngo, Sarnai Amartumur, Van Thi Ai Tran, Minh Tran, Yen N. Diep, Hansang Cho and Luke P. Lee
Biosensors 2023, 13(2), 231; https://doi.org/10.3390/bios13020231 - 6 Feb 2023
Cited by 6 | Viewed by 4657
Abstract
The evolution of preclinical in vitro cancer models has led to the emergence of human cancer-on-chip or microphysiological analysis platforms (MAPs). Although it has numerous advantages compared to other models, cancer-on-chip technology still faces several challenges such as the complexity of the tumor [...] Read more.
The evolution of preclinical in vitro cancer models has led to the emergence of human cancer-on-chip or microphysiological analysis platforms (MAPs). Although it has numerous advantages compared to other models, cancer-on-chip technology still faces several challenges such as the complexity of the tumor microenvironment and integrating multiple organs to be widely accepted in cancer research and therapeutics. In this review, we highlight the advancements in cancer-on-chip technology in recapitulating the vital biological features of various cancer types and their applications in life sciences and high-throughput drug screening. We present advances in reconstituting the tumor microenvironment and modeling cancer stages in breast, brain, and other types of cancer. We also discuss the relevance of MAPs in cancer modeling and precision medicine such as effect of flow on cancer growth and the short culture period compared to clinics. The advanced MAPs provide high-throughput platforms with integrated biosensors to monitor real-time cellular responses applied in drug development. We envision that the integrated cancer MAPs has a promising future with regard to cancer research, including cancer biology, drug discovery, and personalized medicine. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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37 pages, 7994 KiB  
Review
Application of Microfluidics in Drug Development from Traditional Medicine
by Xue Li, Xiaoming Fan, Zhu Li, Lina Shi, Jinkuan Liu, Hongzhi Luo, Lijun Wang, Xiaoxin Du, Wenzhu Chen, Jiuchuan Guo, Chenzhong Li and Shan Liu
Biosensors 2022, 12(10), 870; https://doi.org/10.3390/bios12100870 - 13 Oct 2022
Cited by 16 | Viewed by 3918
Abstract
While there are many clinical drugs for prophylaxis and treatment, the search for those with low or no risk of side effects for the control of infectious and non-infectious diseases is a dilemma that cannot be solved by today’s traditional drug development strategies. [...] Read more.
While there are many clinical drugs for prophylaxis and treatment, the search for those with low or no risk of side effects for the control of infectious and non-infectious diseases is a dilemma that cannot be solved by today’s traditional drug development strategies. The need for new drug development strategies is becoming increasingly important, and the development of new drugs from traditional medicines is the most promising strategy. Many valuable clinical drugs have been developed based on traditional medicine, including drugs with single active ingredients similar to modern drugs and those developed from improved formulations of traditional drugs. However, the problems of traditional isolation and purification and drug screening methods should be addressed for successful drug development from traditional medicine. Advances in microfluidics have not only contributed significantly to classical drug development but have also solved many of the thorny problems of new strategies for developing new drugs from traditional drugs. In this review, we provide an overview of advanced microfluidics and its applications in drug development (drug compound synthesis, drug screening, drug delivery, and drug carrier fabrication) with a focus on its applications in conventional medicine, including the separation and purification of target components in complex samples and screening of active ingredients of conventional drugs. We hope that our review gives better insight into the potential of traditional medicine and the critical role of microfluidics in the drug development process. In addition, the emergence of new ideas and applications will bring about further advances in the field of drug development. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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27 pages, 10424 KiB  
Review
Paper-Based Fluidic Sensing Platforms for β-Adrenergic Agonist Residue Point-of-Care Testing
by Hongzhi Luo, Shan Liu, Lina Shi, Zhu Li, Qianwen Bai, Xiaoxin Du, Lijun Wang, He Zha and Chenzhong Li
Biosensors 2022, 12(7), 518; https://doi.org/10.3390/bios12070518 - 12 Jul 2022
Cited by 4 | Viewed by 2548
Abstract
The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious physiological side effects and even death. Therefore, rapid detection methods for β-adrenergic agonist residues on-site are required. Traditional detection [...] Read more.
The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious physiological side effects and even death. Therefore, rapid detection methods for β-adrenergic agonist residues on-site are required. Traditional detection methods such as liquid chromatography have limitations in terms of expensive instruments and complex operations. In contrast, paper methods are low cost, ubiquitous, and portable, which has led to them becoming the preferred detection method in recent years. Various paper-based fluidic devices have been developed to detect β-adrenergic agonist residues, including lateral flow immunoassays (LFAs) and microfluidic paper-based analytical devices (μPADs). In this review, the application of LFAs for the detection of β-agonists is summarized comprehensively, focusing on the latest advances in novel labeling and detection strategies. The use of μPADs as an analytical platform has attracted interest over the past decade due to their unique advantages and application for detecting β-adrenergic agonists, which are introduced here. Vertical flow immunoassays are also discussed for their shorter assay time and stronger multiplexing capabilities compared with LFAs. Furthermore, the development direction and prospects for the commercialization of paper-based devices are considered, shedding light on the development of point-of-care testing devices for β-adrenergic agonist residue detection. Full article
(This article belongs to the Special Issue Lab on a Chip for High-Throughput Drug Screening)
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