A microfluidic cancer-on-chip platform predicts drug response using organotypic tumor slice culture

We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment.

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Severe Asthma on-Chip: a novel platform enables study of viral-induced exacerbations in asthma and drug response In Vitro

10.1183/1393003.congress-2017.pa4136 ◽

2017 ◽

Cited By ~ 3

Author(s):

Remi Villenave ◽

Carol Lucchesi ◽

Hyun-Hee Lee ◽

Justin Nguyen ◽

Antonio Varone ◽

...

Keyword(s):

Severe Asthma ◽

Drug Response ◽

On Chip

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A microfluidic bubble perfusion device for brain slice culture

Analytical Methods ◽

10.1039/d0ay02291h ◽

2021 ◽

Author(s):

Amirus Saleheen ◽

Debalina Acharyya ◽

Rebecca A. Prosser ◽

Christopher Anthony Baker

Keyword(s):

Brain Slice ◽

Ex Vivo ◽

Analytical Models ◽

Slice Culture ◽

Membrane Interface ◽

Roller Tube ◽

Brain Slice Cultures ◽

Brain Slice Culture ◽

On Chip

Ex vivo brain slice cultures are utilized as analytical models for studying neurophysiology. Common approaches to maintaining slice cultures include roller tube and membrane interface techniques. The rise of organ-on-chip...

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Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer

BMC Cancer ◽

10.1186/s12885-019-6270-4 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Steve Z. Martin ◽

Daniel C. Wagner ◽

Nina Hörner ◽

David Horst ◽

Hauke Lang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Metastatic Colorectal Cancer ◽

Drug Response ◽

Tumor Tissue ◽

Ex Vivo ◽

Tissue Slice ◽

Patient Specific ◽

Slice Culture ◽

Tissue Slices

Abstract Background The lack of predictive biomarkers or test systems contributes to high failure rates of systemic therapy in metastasized colorectal carcinoma, accounting for a still unfavorable prognosis. Here, we present an ex vivo functional assay to measure drug-response based on a tissue slice culture approach. Methods Tumor tissue slices of hepatic metastases of nine patients suffering from colorectal carcinoma were cultivated for 72 h and treated with different concentrations of the clinically relevant drugs Oxaliplatin, Cetuximab and Pembrolizumab. Easy to use, objective and automated analysis routines based on the Halo platform were developed to measure changes in proliferative activity and the morphometric make-up of the tumor. Apoptotic indices were assessed semiquantitatively. Results Untreated tumor tissue slices showed high morphological comparability with the original “in vivo”-tumor, preserving proliferation and stromal-tumor interactions. All but one patients showed a dosage dependent susceptibility to treatment with Oxaliplatin, whereas only two patients showed responses to Cetuximab and Pembrolizumab, respectively. Furthermore, we identified possible non-responders to Cetuximab therapy in absence of RAS-mutations. Conclusions This is the first time to demonstrate feasibility of the tissue slice culture approach for metastatic tissue of colorectal carcinoma. An automated readout of proliferation and tumor-morphometry allows for quantification of drug susceptibility. This strongly indicates a potential value of this technique as a patient-specific test-system of targeted therapy in metastatic colorectal cancer. Co-clinical trials are needed to customize for clinical application and to define adequate read-out cut-off values.

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Microfluidic Protein Imaging Platform: Study of Tau Protein Aggregation and Alzheimer’s Drug Response

Bioengineering ◽

10.3390/bioengineering7040162 ◽

2020 ◽

Vol 7 (4) ◽

pp. 162

Author(s):

Shubha Jain ◽

Sarpras Swain ◽

Lopamudra Das ◽

Sarita Swain ◽

Lopamudra Giri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protein Aggregation ◽

Tau Protein ◽

Drug Response ◽

Drug Evaluation ◽

Confocal Imaging ◽

Tau Imaging ◽

On Chip ◽

Tau Aggregation

Tau protein aggregation is identified as one of the key phenomena associated with the onset and progression of Alzheimer’s disease. In the present study, we performed on-chip confocal imaging of tau protein aggregation and tau–drug interactions using a spiral-shaped passive micromixing platform. Numerical simulations and experiments were performed in order to validate the performance of the micromixer design. We performed molecular modeling of adenosine triphosphate (ATP)-induced tau aggregation in order to successfully validate the concept of helical tau filament formation. Tau aggregation and native tau restoration were realized using an immunofluorescence antibody assay. The dose–response behavior of an Alzheimer’s drug, methylthioninium chloride (MTC), was monitored on-chip for defining the optimum concentration of the drug. The proposed device was tested for reliability and repeatability of on-chip tau imaging. The amount of the tau protein sample used in our experiments was significantly less than the usage for conventional techniques, and the whole protein–drug assay was realized in less than two hours. We identified that intensity-based tau imaging could be used to study Alzheimer’s drug response. In addition, it was demonstrated that cell-free, microfluidic tau protein assays could be used as potential on-chip drug evaluation tools for Alzheimer’s disease.

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Tumor slice culture system to assess drug response of primary breast cancer

BMC Cancer ◽

10.1186/s12885-016-2119-2 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 55

Author(s):

Kishan A. T. Naipal ◽

Nicole S. Verkaik ◽

Humberto Sánchez ◽

Carolien H. M. van Deurzen ◽

Michael A. den Bakker ◽

...

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Culture System ◽

Drug Response ◽

Slice Culture

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Gut microbiome a promising target for management of respiratory diseases

Biochemical Journal ◽

10.1042/bcj20200426 ◽

2020 ◽

Vol 477 (14) ◽

pp. 2679-2696

Author(s):

Riddhi Trivedi ◽

Kalyani Barve

Keyword(s):

Respiratory Diseases ◽

New Technology ◽

Bacterial Flora ◽

Systemic Circulation ◽

The Body ◽

Lung Pathology ◽

Promising Target ◽

Current Therapies ◽

Intestinal Microbial Flora ◽

On Chip

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

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