scholarly journals Microdissected “cuboids” for microfluidic drug testing of intact tissues

Lab on a Chip ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 122-142
Author(s):  
Lisa F. Horowitz ◽  
Adan D. Rodriguez ◽  
Allan Au-Yeung ◽  
Kevin W. Bishop ◽  
Lindsey A. Barner ◽  
...  
Keyword(s):  
Drug Testing ◽  
Multiple Drug ◽  
Microfluidic Platform ◽  
Live Tissue

A microfluidic platform permits multiple drug testing of uniformly-sized microscale “cuboids” of live tissue with well-preserved microenvironments.

scholarly journals A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Neda Dadgar ◽  
Alan M. Gonzalez-Suarez ◽  
Pouria Fattahi ◽  
Xiaonan Hou ◽  
John S. Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Drug Testing ◽  
Microfluidic Devices ◽  
Needle Aspiration ◽  
High Concentration ◽  
Microfluidic Platform ◽  
Drug Concentrations

Abstract There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements. This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids. Six patient-derived xenograft (PDX) tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures. To further demonstrate the potential for miniaturization and multiplexing, we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations. These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device. Overall, we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device. This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited, such as following the acquisition of biopsy specimens obtained by fine-needle aspiration.

scholarly journals Multiplexed drug testing of tumor slices using a microfluidic platform

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
L. F. Horowitz ◽  
A. D. Rodriguez ◽  
Z. Dereli-Korkut ◽  
R. Lin ◽  
K. Castro ◽  
...  
Keyword(s):  
Drug Testing ◽  
Microfluidic Platform

scholarly journals Multiplexed drug testing of tumor slices using a microfluidic platform

2020 ◽  
Author(s):  
L. F. Horowitz ◽  
A.D. Rodriguez ◽  
Z. Dereli-Korkut ◽  
R. Lin ◽  
K. Castro ◽  
...  
Keyword(s):  
Small Molecules ◽  
Drug Testing ◽  
Drug Response ◽  
Cancer Drug ◽  
Cancer Tissue ◽  
Human Glioma ◽  
Microfluidic Platform ◽  
Tissue Microenvironment ◽  
Tumor Biopsies ◽  
Individual Human

ABSTRACTCurrent methods to assess the drug response of individual human cancers are often inaccurate, costly, or slow. Functional approaches that rapidly and directly assess the response of patient cancer tissue to drugs or small molecules offer a promising way to improve drug testing, and have the potential to identify the best therapy for individual patients. We developed a digitally-manufactured microfluidic platform for multiplexed drug testing of intact cancer slice cultures, and demonstrate the use of this platform to evaluate drug responses in slice cultures from human glioma xenografts and patient tumor biopsies. This approach retains much of the tissue microenvironment and can provide results rapidly enough, within days of surgery, to guide the choice of effective initial therapies. Our results establish a useful preclinical platform for cancer drug testing and development with the potential to improve cancer personalized medicine.

scholarly journals A microfluidic platform for functional testing of cancer drugs on intact tumor slices

Lab on a Chip ◽  
2020 ◽  
Vol 20 (9) ◽  
pp. 1658-1675 ◽  
Author(s):  
A. D. Rodriguez ◽  
L. F. Horowitz ◽  
K. Castro ◽  
H. Kenerson ◽  
N. Bhattacharjee ◽  
...  
Keyword(s):  
Drug Testing ◽  
Functional Testing ◽  
Cancer Drugs ◽  
Microfluidic Platform

We have developed a digitally-manufacturable microfluidic platform that allows for multiplexed drug testing of intact tumor slices.

Improved microfluidic platform for simultaneous multiple drug screening towards personalized treatment

2019 ◽  
Vol 123 ◽  
pp. 237-243 ◽  
Author(s):  
Oihane Mitxelena-Iribarren ◽  
Jon Zabalo ◽  
Sergio Arana ◽  
Maite Mujika
Keyword(s):  
Drug Screening ◽  
Personalized Treatment ◽  
Multiple Drug ◽  
Microfluidic Platform

scholarly journals Pumpless microfluidic platform for drug testing on human skin equivalents

Lab on a Chip ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. 882-888 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Karl Gledhill ◽  
Zongyou Guo ◽  
Angela M. Christiano ◽  
Michael L. Shuler
Keyword(s):  
Human Skin ◽  
Drug Screening ◽  
Drug Testing ◽  
Microfluidic Platform ◽  
Skin Equivalents ◽  
Human Skin Models

Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies.

Oral Fluid Drug Testing: Analytical Approaches, Issues and Interpretation of Results

2019 ◽  
Vol 43 (6) ◽  
pp. 415-443 ◽  
Author(s):  
Nathalie A Desrosiers ◽  
Marilyn A Huestis
Keyword(s):  
Analytical Methods ◽  
Drug Testing ◽  
Oral Fluid ◽  
Driving Under The Influence ◽  
Multiple Drug ◽  
Blood Concentrations ◽  
The Past ◽  
Drug Classes ◽  
Drug Concentrations ◽  
Analytical Approaches

AbstractWith advances in analytical technology and new research informing result interpretation, oral fluid (OF) testing has gained acceptance over the past decades as an alternative biological matrix for detecting drugs in forensic and clinical settings. OF testing offers simple, rapid, non-invasive, observed specimen collection. This article offers a review of the scientific literature covering analytical methods and interpretation published over the past two decades for amphetamines, cannabis, cocaine, opioids, and benzodiazepines. Several analytical methods have been published for individual drug classes and, increasingly, for multiple drug classes. The method of OF collection can have a significant impact on the resultant drug concentration. Drug concentrations for amphetamines, cannabis, cocaine, opioids, and benzodiazepines are reviewed in the context of the dosing condition and the collection method. Time of last detection is evaluated against several agencies' cutoffs, including the proposed Substance Abuse and Mental Health Services Administration, European Workplace Drug Testing Society and Driving Under the Influence of Drugs, Alcohol and Medicines cutoffs. A significant correlation was frequently observed between matrices (i.e., between OF and plasma or blood concentrations); however, high intra-subject and inter-subject variability precludes prediction of blood concentrations from OF concentrations. This article will assist individuals in understanding the relative merits and limitations of various methods of OF collection, analysis and interpretation.

scholarly journals Drug-related relapses in drug reaction with eosinophilia and systemic symptoms (DRESS)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lukas Jörg ◽  
Arthur Helbling ◽  
Daniel Yerly ◽  
Werner J. Pichler
Keyword(s):  
Drug Reaction ◽  
Drug Testing ◽  
Drug Hypersensitivity ◽  
Lymphocyte Transformation ◽  
Lymphocyte Transformation Test ◽  
New Drugs ◽  
University Hospital ◽  
Skin Tests ◽  
Multiple Drug ◽  
Systemic Symptoms

Abstract Background A drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T cell mediated hypersensitivity reaction. Relapses of symptoms in the recovery phase are frequent and linked to the reduction of the corticosteroid treatment, to viral reactivations or to the exposure to new drugs. Here, we analyzed, how often the exposure to new drugs leads to new sensitization or drug-related relapses without detectable sensitization. Methods 46 patients with DRESS treated in the allergy division of the Inselspital, Bern University Hospital, were retrospectively assessed. Drug-related relapses were analyzed in terms of frequency and whether a possible sensitization evaluated by skin tests and/or lymphocyte transformation tests (LTT) to the new drugs was detectable. Furthermore, drug tolerance was evaluated in a subset of patients. Results 56 relapses were observed in 27 of 46 patients with DRESS (58.7%). 33 (58.9%) of these relapses were associated with the use of new drugs, 30 drug-related relapses were evaluated by patch test and/or lymphocyte transformation test. In 8/30 (26.7%) drug-related relapses, a sensitization to the new drug was demonstrated, suggesting the emergence of a multiple drug hypersensitivity syndrome (MDH). 14 patients experienced 22 drug-related relapses without any detectable sensitization and only 1/6 patients developed new symptoms upon reexposure. Conclusion Patients with DRESS frequently suffered from drug related relapses. Half of the patients with drug-related relapses developed a MDH with proven sensitizations not only to the DRESS inducing drugs, but also to newly applied drugs. When not sensitized, drugs involved in drug related relapses could be reintroduced, if needed. Here, we propose a procedure for drug testing and future management of drug-related relapses in DRESS.

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