A microfluidics platform for combinatorial drug screening on cancer biopsies

Eduati, Federica; Utharala, Ramesh; Madhavan, Dharanija; Neumann, Ulf; Longerich, Thomas; Cramer, Thorsten; Sáez-Rodríguez, Julio; Merten, Christoph A.

doi:10.1038/s41467-018-04919-w

Cited by 204 publications

(174 citation statements)

References 46 publications

(61 reference statements)

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“…In order to monitor treatment responses, CTCs from patient blood can be isolated using microfluidic devices . Applying, for example, a combination of valve and droplet technology to read apoptosis or a series of suspended microchannel resonators (SMRs) to measure mass accumulation rate (MAR), will allow drug susceptibilities of isolated primary tumor cells or CTCs to be determined. In parallel, isolated tumor cells can be applied to various genetic tests to predict potent drugs from patients' genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…To further push the throughput and also to enable the screening of drug combinations, we recently described a droplet microfluidic system that can produce in a sequential manner drug cocktails, paired with fluorescent barcodes ( Figure A). The screening of drug combinations is of particular interest because they are often more efficient than monotherapies, especially in overcoming resistances.…”

Section: Phenotypic Testing Of Patient Cancer Cellsmentioning

confidence: 99%

“…Target agnostic and biomarker‐independent testing of drugs directly on very limited patient material. A) Combinatorial drug screening in nanoliter plugs . a) Microfluidic design of the chip including the inputs into chip color coded, respectively.…”

Section: Phenotypic Testing Of Patient Cancer Cellsmentioning

confidence: 99%

“…c) Combinatorial plugs containing patient cancer cells, drug combinations, and all reagents of a fluorescence assay for apoptosis were generated in an automated fashion and stored sequentially in PTFE tubing of length of 5 m. d) After overnight incubation, multicolor fluorescence analysis of the sample plugs was carried out to determine drug efficacy in a personalized approach. Apapted under the terms of a Creative Commons Attribution 4.0 International License . Copyright 2018, The Authors, published by Springer Nature.…”

Section: Phenotypic Testing Of Patient Cancer Cellsmentioning

confidence: 99%

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Microfluidics as an Enabling Technology for Personalized Cancer Therapy

Mathur

Ballinger

Utharala

et al. 2019

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Tailoring patient‐specific treatments for cancer is necessary in order to achieve optimal results but requires new diagnostic approaches at affordable prices. Microfluidics has immense potential to provide solutions for this, as it enables the processing of samples that are not available in large quantities (e.g., cells from patient biopsies), is cost efficient, provides a high level of automation, and allows the set‐up of complex models for cancer studies. In this review, individual solutions in the fields of genetics, circulating tumor cell monitoring, biomarker analysis, phenotypic drug sensitivity tests, and systems providing controlled environments for disease modeling are discussed. An overview on how these early stage achievements can be combined or developed further is showcased, and the required translational steps before microfluidics becomes a routine tool for clinical applications are critically discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Phenotypic Testing Of Patient Cancer Cellsmentioning

confidence: 99%

Section: Phenotypic Testing Of Patient Cancer Cellsmentioning

confidence: 99%

Section: Phenotypic Testing Of Patient Cancer Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Microfluidics as an Enabling Technology for Personalized Cancer Therapy

Mathur

Ballinger

Utharala

et al. 2019

Small

Self Cite

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“…The problem of insufficient cell material available for DSRT can be solved by using miniaturized platforms based on technologies alternative to microtiter plates. There are numerous studies demonstrating utilization of such platforms for screening of live mammalian cells, however few of them are focused on screening of patient‐derived cells with a goal of defining appropriate therapy for cancer patients . Some examples of such studies are given below and summarized in Table .…”

Section: Miniaturized Systems For Dsrt On 2d Cell Culture Modelsmentioning

confidence: 99%

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

Popova

Levkin

2020

Advanced Therapeutics

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Precision or personalized medicine aims to determine an optimal therapy for each individual patient. In oncology techniques such as next generation sequencing, mRNA‐sequencing, ChIP‐sequencing, and mass spectrometry are used to perform a full molecular profiling for each patient. However, it is not always possible to determine a suitable treatment for an individual cancer based on molecular profiling, mostly due to the high level of tumor heterogeneity. In vitro drug sensitivity and resistance test (DSRT) can be performed on cancer cells or tissues obtained from a patient with a panel of anticancer compounds in order to experimentally define sensitivity and resistance of each individual cancer. In combination with molecular profiling, DSRT can provide a fuller picture about the nature of disease, allowing for finding more appropriate therapy for each individual patient. In this progress report, studies describing in vitro DSRTs on 2D and 3D cell models based on patient‐derived cells are reviewed and challenges and future steps needed for the adaptation of these systems in clinics are discussed.

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Paper‐Like Writable Nanoparticle Network Sheets for Mask‐Less MOF Patterning

Taheri

Chen

et al. 2021

Adv Funct Materials

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Geometrical structuring of monolithic metal‐organic frameworks (MOFs) components is required for their practical implementation in many areas, including electronic devices, gas storage/separation, catalysis, energy storage as well as bio‐medical applications. Despite progress in structuring MOFs, an approach for the precise patterning of MOF functional geometries in the millimeter‐ to micro‐meter depth is lacking. Here, a facile and flexible concept for the microfabrication of complex MOF patterns on large surfaces is reported. The method relies on the engineering of easily‐writable sheets of precursor metal oxide nanoparticles. The gas‐phase conversion of these patterned ceramic nanoparticle sheets results in monolithic MOF objects with arbitrarily shaped geometries and thicknesses of up to hundreds of micrometers. The writing of complex patterns of zeolitic imidazolate framework‐8 (ZIF‐8) is demonstrated by a variety of approaches including ion beam, laser, and hand writing. Nanometer‐scale patterns are achieved by focused ion beam (FIB). Artless handwritings are obtained by using a pen in a similar fashion to writing on a paper. The pure ZIF‐8 composition of the resulting patterns is confirmed by a series of physical and chemical characterization. This facile MOF precursor‐writing approach provides novel opportunities for the design of MOF‐based devices with applications ranging from micro‐fluidics to renewable energy systems.

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A microfluidics platform for combinatorial drug screening on cancer biopsies

Cited by 204 publications

References 46 publications

Microfluidics as an Enabling Technology for Personalized Cancer Therapy

Microfluidics as an Enabling Technology for Personalized Cancer Therapy

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

Paper‐Like Writable Nanoparticle Network Sheets for Mask‐Less MOF Patterning

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