A cost-effective fluorescence mini-microscope for biomedical applications

Zhang, Yu Shrike; Ribas, João Francisco Magno; Nadhman, Akhtar; Aleman, Julio; Selimović, Šeila; Lesher‐Pérez, Sasha Cai; Wang, Ting; Manoharan, Vijayan; Shin, Su Ryon; Damilano, Alessia; Annabi, Nasim; Dokmeci, Mehmet R.; Takayama, Shuichi; Khademhosseini, Ali

doi:10.1039/c5lc00666j

Cited by 89 publications

(92 citation statements)

References 53 publications

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“…S20B). The oxygen-quenchable luminescent dye [Ru(dpp) 3 ] 2+ Cl 2 -tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) chloride (Sigma-Aldrich), with an excitation wavelength at 463 nm and a maximum emission at 618 nm, was used for the oxygen sensor (53). The detailed procedures are described in SI Appendix.…”

Section: Integration Of the Microelectrode Set With Microfluidic Elecmentioning

confidence: 99%

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

Zhang

Aleman

Shin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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634

571

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Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.organ-on-a-chip | microbioreactor | electrochemical biosensor | physical sensor | drug screening D rug discovery is a lengthy process associated with tremendous cost and high failure rate (1). On average, less than 1 in 10 drug candidates are eventually approved by the Food and Drug Administration (2), during which successful transition ratios to next phases are roughly 65, 32, and 60% for phase I, phase II, and phase III, respectively (3). Among the primary causes of failure, nonclinical/ clinical safety (>50%) and efficacy (>10%) stand out in the front, more than all other factors (e.g., strategic, commercial, operational) combined (3, 4). These two major causes not only contribute to the low success rates during the drug development but also lead to the withdrawal of approved drugs from the market. Among all of the drug attritions, it is estimated that safety liabilities related to the cardiovascular system account for 45%, whereas 32% are due to hepatotoxicity (5, 6). These high failure/attrition ratios of drugs SignificanceMonitoring human organ-on-a-chip systems presents a significant challenge, where the capability of in situ continual monitoring of organ behaviors and their responses to pharmaceutical compounds over extended periods of time is critical in understanding the dynamics of drug effects and therefore accurate prediction of human organ reacti...

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Section: Integration Of the Microelectrode Set With Microfluidic Elecmentioning

confidence: 99%

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

Zhang

Aleman

Shin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

634

571

View full text Add to dashboard Cite

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“…21 Thus, it is important to monitor the physicochemical parameters within the culture medium. [22][23][24] In addition, proper control of the oxygen tension is a critical task for multi-organon-chip microsystems, 9,25,26 where each organ construct may need a unique microenvironment with special levels of dissolved oxygen. 17 Hence, the development of microfluidic platforms with integrated multi-analyte sensing capabilities for in-line monitoring of physicochemical parameters of organ constructs is needed to fully enable the use of organs-on-chip microsystems for in vitro analysis of cellular functions.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices

et al. 2016

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There is a growing interest to develop microfluidic bioreactors and organ-on-chip platforms with integrated sensors to monitor their physicochemical properties and to maintain a well-controlled microenvironment for cultured organoids. Conventional sensing devices cannot be easily integrated with microfluidic organ-on-chip systems with low-volume bioreactors for continual monitoring. This paper reports on the development of a multi-analyte optical sensing module for dynamic measurements of pH and dissolved oxygen levels in the culture medium. The sensing system was constructed using low-cost electro-optics including light-emitting diodes and silicon photodiodes. The sensing module includes an optically transparent window for measuring light intensity, and the module could be connected directly to a perfusion bioreactor without any specific modifications to the microfluidic device design. A compact, user-friendly, and low-cost electronic interface was developed to control the optical transducer and signal acquisition from photodiodes. The platform enabled convenient integration of the optical sensing module with a microfluidic bioreactor. Human dermal fibroblasts were cultivated in the bioreactor, and the values of pH and dissolved oxygen levels in the flowing culture medium were measured continuously for up to 3 days. Our integrated microfluidic system provides a new analytical platform with ease of fabrication and operation, which can be adapted for applications in various microfluidic cell culture and organ-on-chip devices.

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“…Indeed, growing efforts have been made to develop compact imaging systems so that cell functional assays can be performed without requiring specialized microscopy facilities. For example, various incubation microscopes were developed so the microscope can be placed inside a conventional incubator for cell imaging or directly control the temperature of the cell assay within the portable microscope (Jin et al 2015;Pushkarsky et al 2014;Walzik et al 2015;Zhang et al 2015). A highly integrated portable and robotically controlled live cell imaging system was employed for cell migration assay in a microfluidic device (Saito et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Mkit: A cell migration assay based on microfluidic device and smartphone

Yang

Peretz‐Soroka

et al. 2018

Biosensors and Bioelectronics

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Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS 2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS 2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS 2 -based cell functional assay for testing cell migration (the M kit ). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the M kit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the M kit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the M kit . In addition to research applications, we demonstrated the effective use of the M kit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed M kit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications.

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A cost-effective fluorescence mini-microscope for biomedical applications

Cited by 89 publications

References 53 publications

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices

Mkit: A cell migration assay based on microfluidic device and smartphone

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