title: A microfluidic platform for drug screening in a 3D cancer microenvironment.
abstract: Development of resistance to chemotherapy treatments is a major challenge in the battle against cancer. Although a vast repertoire of chemotherapeutics is currently available for treating cancer, a technique for rapidly identifying the right drug based on the chemo-resistivity of the cancer cells is not available and it currently takes weeks to months to evaluate the response of cancer patients to a drug. A sensitive, low-cost diagnostic assay capable of rapidly evaluating the effect of a series of drugs on cancer cells can significantly change the paradigm in cancer treatment management. Integration of microfluidics and electrical sensing modality in a 3D tumour microenvironment may provide a powerful platform to tackle this issue. Here, we report a 3D microfluidic platform that could be potentially used for a real-time deterministic analysis of the success rate of a chemotherapeutic drug in less than 12h. The platform (66mm×50mm; L×W) is integrated with the microsensors (interdigitated gold electrodes with width and spacing 10µm) that can measure the change in the electrical response of cancer cells seeded in a 3D extra cellular matrix when a chemotherapeutic drug is flown next to the matrix. B16-F10 mouse melanoma, 4T1 mouse breast cancer, and DU 145 human prostate cancer cells were used as clinical models. The change in impedance magnitude on flowing chemotherapeutics drugs measured at 12h for drug-susceptible and drug tolerant breast cancer cells compared to control were 50,552±144 Ω and 28,786±233 Ω, respectively, while that of drug-susceptible melanoma cells were 40,197±222 Ω and 4069±79 Ω, respectively. In case of prostate cancer the impedance change between susceptible and resistant cells were 8971±1515 Ω and 3281±429 Ω, respectively, which demonstrated that the microfluidic platform was capable of delineating drug susceptible cells, drug tolerant, and drug resistant cells in less than 12h.
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hardik J
authors.initials: HJ
authors.lastname: Pandya
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Karan
authors.initials: K
authors.lastname: Dhingra
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Devbalaji
authors.initials: D
authors.lastname: Prabhakar
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Vineethkrishna
authors.initials: V
authors.lastname: Chandrasekar
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Siva Kumar
authors.initials: SK
authors.lastname: Natarajan
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anish S
authors.initials: AS
authors.lastname: Vasan
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA. Electronic address: akulkarni@bwh.harvard.edu.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: hshafiee@bwh.harvard.edu.
authors.forename: Hadi
authors.initials: H
authors.lastname: Shafiee
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D018929:Cell Culture Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D044085:Microfluidics / Q000379:methods*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics
keywords: Cancer microenvironment; Chemotherapy; Drug screening; Electrical sensing; Microfluidics