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Micromachines
Special Issues
Unlocking the Next Level in Precision Medicine with Organ-on-Chips and...
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Unlocking the Next Level in Precision Medicine with Organ-on-Chips and Biosensors

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B1: Biosensors".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 17106

Special Issue Editors

Dr. Riccardo Barrile

E-Mail Website
Guest Editor
Engineering Research Center, University of Cincinnati, Cincinnati, OH 45221, USA
Interests: personalized bioengineering; organ-on-chip; vascularized microtissues; preclinical models; bioprinting; cerebrovascular biology
Dr. Magdalena Kasendra

E-Mail Website
Guest Editor
Center for Stem Cell and Organoid Medicine (CuSTOM) Accelerator, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Interests: organoids; organs-on-chips; stem cell biology; disease modeling; biomarker and therapeutic discovery; regenerative medicine

Special Issue Information

Dear Colleagues,

Realization of a simple and yet powerful idea of personalized medicine has inspired a major progress in biomedical research over the past two decades. However, despite remarkable progress in medicine and “omics” (genomics, proteomics, metabolomics) that has occurred since the completion of the human genome project, only a few personalized medicine applications have been successfully translated into clinical practice. Reasons for such a poor outcome include the exploratory and retrospective nature of many “-omics” studies, the complexity of these assays and their application to clinical specimens, as well as the lack of personalized and predictive preclinical models that could confirm the predictive value of the “omics” findings.

Recent integration of stem cell biology and microfluidics has allowed researchers to demonstrate the utility of a variety of organ-on-chip models to capture donors’ health and susceptibility to drugs. This has paved the way toward development of in vitro platforms for personalized safety and efficacy, which could bridge the gap between preclinical and clinical drug development. Another approach to precision medicine has been created at the intersection of microfluidic technology and biosensing. This has led to the development of novel point-of-care and wearable devices that can detect predictive biomarkers in various human specimens, including blood, saliva or sweat. These tools enable real-time and precise monitoring of patients’ health and response to drugs, which could be ultimately adopted to assess drug pharmacokinetics in a patient-specific manner.

Bioengineering approaches that employ the use of microfluidic platforms and biosensors for precise and real-time monitoring of patient-specific factors, conditions, and responses represent a major stepping stone toward realization of the full potential of precision medicine.

This Special Issue of Micromachines aims at reviewing the current state-of-the-art of these technologies and presenting perspectives for future research and development efforts required for translation into the clinic. Contributions related to non-microfluidics technologies that apply bioengineering methods to harness the full potential of stem cell biology and/or development of innovative biosensing technologies to realize the full potential of precision medicine are welcome.

Papers in all areas of organ-on-chip technology, development of personalized tissue models, and biosensors will be considered, including but not limited to:

  • Stem cell derived organs-on-chips;
  • Organoids derived organs-on-chips;
  • Real time sensing of biomarkers;
  • Innovative microfabrication methods;
  • Organs-on-chips and bio-printed micro tissues for de-risking of drug-induced toxicity and prediction of drug efficacy.

Dr. Riccardo Barrile
Dr. Magdalena Kasendra
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Stem-cell-derived organs-on-chips
  • biosensors
  • wearable devices
  • point of care
  • personalized bioengineering
  • precision medicine

Published Papers (4 papers)

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Research

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12 pages, 2742 KiB  
Article
In Situ Vitrification of Lung Cancer Organoids on a Microwell Array
by Qiang Liu, Tian Zhao, Xianning Wang, Zhongyao Chen, Yawei Hu and Xiaofang Chen
Micromachines 2021, 12(6), 624; https://doi.org/10.3390/mi12060624 - 28 May 2021
Cited by 13 | Viewed by 3571
Abstract
Three-dimensional cultured patient-derived cancer organoids (PDOs) represent a powerful tool for anti-cancer drug development due to their similarity to the in vivo tumor tissues. However, the culture and manipulation of PDOs is more difficult than 2D cultured cell lines due to the presence [...] Read more.
Three-dimensional cultured patient-derived cancer organoids (PDOs) represent a powerful tool for anti-cancer drug development due to their similarity to the in vivo tumor tissues. However, the culture and manipulation of PDOs is more difficult than 2D cultured cell lines due to the presence of the culture matrix and the 3D feature of the organoids. In our other study, we established a method for lung cancer organoid (LCO)-based drug sensitivity tests on the superhydrophobic microwell array chip (SMAR-chip). Here, we describe a novel in situ cryopreservation technology on the SMAR-chip to preserve the viability of the organoids for future drug sensitivity tests. We compared two cryopreservation approaches (slow freezing and vitrification) and demonstrated that vitrification performed better at preserving the viability of LCOs. Next, we developed a simple procedure for in situ cryopreservation and thawing of the LCOs on the SMAR-chip. We proved that the on-chip cryopreserved organoids can be recovered successfully and, more importantly, showing similar responses to anti-cancer drugs as the unfrozen controls. This in situ vitrification technology eliminated the harvesting and centrifugation steps in conventional cryopreservation, making the whole freeze–thaw process easier to perform and the preserved LCOs ready to be used for the subsequent drug sensitivity test. Full article
(This article belongs to the Special Issue Unlocking the Next Level in Precision Medicine with Organ-on-Chips and Biosensors)
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Review

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32 pages, 4842 KiB  
Review
Modelling Human Physiology on-Chip: Historical Perspectives and Future Directions
by Sirjana Pun, Li Cai Haney and Riccardo Barrile
Micromachines 2021, 12(10), 1250; https://doi.org/10.3390/mi12101250 - 15 Oct 2021
Cited by 11 | Viewed by 4681
Abstract
For centuries, animal experiments have contributed much to our understanding of mechanisms of human disease, but their value in predicting the effectiveness of drug treatments in the clinic has remained controversial. Animal models, including genetically modified ones and experimentally induced pathologies, often do [...] Read more.
For centuries, animal experiments have contributed much to our understanding of mechanisms of human disease, but their value in predicting the effectiveness of drug treatments in the clinic has remained controversial. Animal models, including genetically modified ones and experimentally induced pathologies, often do not accurately reflect disease in humans, and therefore do not predict with sufficient certainty what will happen in humans. Organ-on-chip (OOC) technology and bioengineered tissues have emerged as promising alternatives to traditional animal testing for a wide range of applications in biological defence, drug discovery and development, and precision medicine, offering a potential alternative. Recent technological breakthroughs in stem cell and organoid biology, OOC technology, and 3D bioprinting have all contributed to a tremendous progress in our ability to design, assemble and manufacture living organ biomimetic systems that more accurately reflect the structural and functional characteristics of human tissue in vitro, and enable improved predictions of human responses to drugs and environmental stimuli. Here, we provide a historical perspective on the evolution of the field of bioengineering, focusing on the most salient milestones that enabled control of internal and external cell microenvironment. We introduce the concepts of OOCs and Microphysiological systems (MPSs), review various chip designs and microfabrication methods used to construct OOCs, focusing on blood-brain barrier as an example, and discuss existing challenges and limitations. Finally, we provide an overview on emerging strategies for 3D bioprinting of MPSs and comment on the potential role of these devices in precision medicine. Full article
(This article belongs to the Special Issue Unlocking the Next Level in Precision Medicine with Organ-on-Chips and Biosensors)
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25 pages, 2109 KiB  
Review
Progress and Challenges in the Use of a Liver-on-a-Chip for Hepatotropic Infectious Diseases
by Kasem Kulkeaw and Worakamol Pengsart
Micromachines 2021, 12(7), 842; https://doi.org/10.3390/mi12070842 - 19 Jul 2021
Cited by 8 | Viewed by 3942
Abstract
The liver is a target organ of life-threatening pathogens and prominently contributes to the variation in drug responses and drug-induced liver injury among patients. Currently available drugs significantly decrease the morbidity and mortality of liver-dwelling pathogens worldwide; however, emerging clinical evidence reveals the [...] Read more.
The liver is a target organ of life-threatening pathogens and prominently contributes to the variation in drug responses and drug-induced liver injury among patients. Currently available drugs significantly decrease the morbidity and mortality of liver-dwelling pathogens worldwide; however, emerging clinical evidence reveals the importance of host factors in the design of safe and effective therapies for individuals, known as personalized medicine. Given the primary adherence of cells in conventional two-dimensional culture, the use of these one-size-fit-to-all models in preclinical drug development can lead to substantial failures in assessing therapeutic safety and efficacy. Advances in stem cell biology, bioengineering and material sciences allow us to develop a more physiologically relevant model that is capable of recapitulating the human liver. This report reviews the current use of liver-on-a-chip models of hepatotropic infectious diseases in the context of precision medicine including hepatitis virus and malaria parasites, assesses patient-specific responses to antiviral drugs, and designs personalized therapeutic treatments to address the need for a personalized liver-like model. Second, most organs-on-chips lack a monitoring system for cell functions in real time; thus, the review discusses recent advances and challenges in combining liver-on-a-chip technology with biosensors for assessing hepatocyte viability and functions. Prospectively, the biosensor-integrated liver-on-a-chip device would provide novel biological insights that could accelerate the development of novel therapeutic compounds. Full article
(This article belongs to the Special Issue Unlocking the Next Level in Precision Medicine with Organ-on-Chips and Biosensors)
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19 pages, 29714 KiB  
Review
Cystic Fibrosis Human Organs-on-a-Chip
by Herbert Luke Ogden, Hoyeol Kim, Kathryn A. Wikenheiser-Brokamp, Anjaparavanda P. Naren and Kyu Shik Mun
Micromachines 2021, 12(7), 747; https://doi.org/10.3390/mi12070747 - 25 Jun 2021
Cited by 10 | Viewed by 4187
Abstract
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene: the gene product responsible for transporting chloride and bicarbonate ions through the apical membrane of most epithelial cells. Major clinical features of CF include [...] Read more.
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene: the gene product responsible for transporting chloride and bicarbonate ions through the apical membrane of most epithelial cells. Major clinical features of CF include respiratory failure, pancreatic exocrine insufficiency, and intestinal disease. Many CF animal models have been generated, but some models fail to fully capture the phenotypic manifestations of human CF disease. Other models that better capture the key characteristics of the human CF phenotype are cost prohibitive or require special care to maintain. Important differences have been reported between the pathophysiology seen in human CF patients and in animal models. These limitations present significant limitations to translational research. This review outlines the study of CF using patient-derived organs-on-a-chip to overcome some of these limitations. Recently developed microfluidic-based organs-on-a-chip provide a human experimental model that allows researchers to manipulate environmental factors and mimic in vivo conditions. These chips may be scaled to support pharmaceutical studies and may also be used to study organ systems and human disease. The use of these chips in CF discovery science enables researchers to avoid the barriers inherent in animal models and promote the advancement of personalized medicine. Full article
(This article belongs to the Special Issue Unlocking the Next Level in Precision Medicine with Organ-on-Chips and Biosensors)
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