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. 2022 Aug 3;12:960340. doi: 10.3389/fonc.2022.960340

Table 3.

Microfluidic Devices in H&N Cancer Research.

Author Aim Drug Stimulant Culture Model Design and Components Analytic Outputs Main Findings
Single vs. Multicellular Cultures Primary vs. Cell Lines 2D vs. 3D Geometry Hypoxic Cues
Hattersley et al. (49) A dynamic culture method as chemotherapy screening platform -5-FU
-Cisplatin
Single Primary:
Patient-derived H&N squamous cell carcinoma
Cell lines:
-NS
2D:
Unexposed control
Dynamic flow
3D:
Multimicro channels Dynamic flow
Syringe pump
NS -H&E staining
-Lactose dehydrogenase release
-WST-1 metabolism
-Trypan blue
-Cytochrome C analysis
-Preclinical model for personalized medicine and testing
-H&E staining showed the retention of multilayer tissue strata
-Combination therapy presented higher levels of cytochrome C compared to untreated control
Riley et al. (91) A dynamic culture method as drug screening platform -Etoposide (topoisomerase II inhibitor)
-SP600125 (JNK inhibitor)
Single Primary:
Human thyroid tissue samples
Cell lines:
-NS
2D:
Unexposed control
Dynamic flow
3D:
Tissue chamber
Dynamic flow
Syringe pump
NS -Hematoxylin and eosin
-Flow cytometry
-Trypan blue
-Immunohistochemistry staining
-Functional analysis
- Lactose dehydrogenase release
-TUNEL assay
-Immunoblot analysis
-Preclinical model for personalized medicine and testing
-H&E staining showed the retention of multilayer tissue strata
-Thyroid biopsies were considered functional due to the production of T4 during the culture period
-Increased apoptosis on thyroid samples after the perfusion of both drugs in comparison to untreated control
Al-Samadi et al. (92) A dynamic culture method as drug screening platform -PDL1 antibody
-IDO1 inhibitor
Single Primary:
Primary H&N squamous cell carcinomas,
T cells, B cells, NK cells, monocytes, and dendritic cells
Cell lines:
-HSC-3
2D:
Unexposed control
Dynamic flow
3D:
Chambers coated with ECM substitute
Dynamic flow
Unspecified pump
NS -Migration assay
-Immunofluorescence staining
- CellTiter 96® Proliferation Assay
-Cell Trace kit
-Preclinical organotypic model for personalized medicine and testing
-IDO 1 inhibitor influences immune cell migration to cancer cells
-Therapy response was reported to be patient dependent
Bower et al. (94) A dynamic culture method as maintenance platform NS Single Primary:
Human biopsies of laryngeal, oropharyngeal, or oral cavity tumors staged at T2–T4
Cell lines:
-NS
2D:
Unexposed control
Dynamic flow
3D:
Biopsy chamber
Dynamic flow
Syringe pump
NS -H&E staining
-Trypan blue
-Flow cytometry
-MTS proliferation assay
-Patient-derived samples were viable for 48 h after placement in the microfluidic chip
-No significance difference concerning the average proliferation of samples pre- and postcultured in the chip
Lugo-Cintrón et al. (95) A dynamic culture method as angiogenesis platform NS Two-culture Primary:
Human tubular lymphatic vessels and cancer-associated fibroblasts
Cell lines:
-HLEC2500
-HOrF2640
2D:
Unexposed control
Dynamic flow
3D:
Collagen hydrogel adhesion chamber
Dynamic flow
Syringe pump
NS -H&E staining
-Immunofluorescence staining
-Immunohistochemistry staining
-Proliferation assay
-Migration and permeability assay
-RT-qPCR
-Multiphoton microscopy
-Preclinical organotypic model for personalized medicine and testing
-Cancer-associated fibroblasts increased the gene expression of prolymphangiogenic factors in the lymphatic-like vessels
Sharafeldin et al. (96) A dynamic culture method as biomarker detection platform NS Single Primary:
NS
Cell lines:
-HN12
-HN13
-HN30
-CAL-27
2D:
Subtract biomarker control signal
3D:
Sonic-assisted chemical lysis chambers
Dynamic flow
peristaltic micropump
NS -Biomarker quantification (desmoglein 3, VEGF-A,VEGF-C, β-Tub) -Biomarker detection model for cancer metastasis diagnostic
-Limit of detection was below 0.20 fg/ml of the analyzed analyte in 20-min evaluation
Jin et al. (103) A dynamic culture method as a chemotherapy screening platform -Paclitaxel
-Cisplatin
-5-FU
Two-culture Primary:
Patient-derived tumor cells from squamous cell carcinoma and salivary gland adenoid
cystic carcinoma
Cell lines:
-ACC-M
-UM-SCC-6
-HUVEC
2D:
NS
3D:
Transwell-like channels
-Bottom chambers coated with an ECM substitute
Dynamic flow
Double syringe pump
NS -Hoechst 33342 and propidium iodide
-Immunofluorescence staining
-Preclinical organotypic model for personalized medicine and testing
-High concentration of drugs did not provide a therapeutic effect as HUVEC cells were killed. A lower concentration was recommended to provide a therapy to kill cancer cells (over 50% apoptosis) and low HUVEC cytotoxicity (over 50% viability)
-Therapy response was reported to be patient dependent concerning different low drug concentrations

NS, not studied.