Parallel and large‐scale antitumor investigation using stable chemical gradient and heterotypic three‐dimensional tumor coculture in a multi‐layered microfluidic device

Abstract

Background: Cancer has been responsible for a large number of human deaths in the 21st century. Establishing a controllable, biomimetic, and large-scale analytical platform to investigate the tumor-associated pathophysiological and preclinical events, such as oncogenesis and chemotherapy, is necessary. Methods and Results:This study presents antitumor investigation in a parallel, largescale, and tissue-mimicking manner based on well-constructed chemical gradients and heterotypic three-dimensional (3D) tumor cocultures using a multifunctionintegrated device. The integrated microfluidic device was engineered to produce a controllable and steady chemical gradient by manipulative optimization. Array-like and size-homogeneous production of heterotypic 3D tumor cocultures with in vivolike features, including similar tumor-stromal composition and functional phenotypic gradients of metabolic activity and viability, was successfully established. Furthermore, temporal, parallel, and high-throughput analyses of tumor behaviors in different antitumor stimulations were performed in a device based on the integrated operations involving gradient generation and coculture. Conclusion:This achievement holds great potential for applications in the establishment of multifunctional tumor platforms to perform tissue-biomimetic neoplastic research and therapy assessment in the fields of oncology, bioengineering, and drug discovery.

Glioma Single-Cell Biomechanical Analysis by Cyclic Conical Constricted Microfluidics

“…Moreover, the time-consuming IHC or genetic sequencing analysis would take up to over 3 days of processing time to achieve a premium conclusion, which can never facilitate the surgery or postsurgical treatment. Instead of conducting the costly full genetic analysis of tumor tissue, the microfluidics-assisted single-cell analysis is identified effective in providing partial biophysical characteristics in tumor diagnosis. − …”

Microfluidic devices: The application in TME modeling and the potential in immunotherapy optimization

“…With the continuous progression over the past years, microfluidic devices, based on microfluidic technology, have been developed to recapitulate the physiological and pathological condition of humans in vitro ( Hassell et al, 2017 ). Microfluidic devices have significant advantages in imitating not only vascular perfusion, air-liquid interfaces, shear stresses as well as the physical and chemical gradients of physical conditions, but also the mechanical activity within organs or tissues of humans ( Choi et al, 2015 ; Murugesan et al, 2017 ; Liu et al, 2021 ). As for the imitation of pathological conditions, microfluidic devices are mainly applicated in modeling the TME of tumor progression.…”

“…Microfluidic chips, made of optical plastic, glass, PDMS, or other special polymers, are microfluidic devices designed for cell culture. Different from traditional 2D cell culture models, organ chips with microchannels allowed the fluids to flow across the cell chambers, which enabled the recapitulation for in vivo physical conditions such as vascular perfusion, air-liquid interfaces, shear stresses as well as the physical and chemical gradients ( Murugesan et al, 2017 ; Liu et al, 2021 ). For instance, microfluidic chips were used to culture the human‐induced pluripotent stem cells (hiPSCs)‐derived hepatocytes-like cells (HLCs) ( Danoy et al, 2021 ).…”

A review on biomimetic models based on microfluidic devices for drug research

“…Among the 19 papers reviewed (Table 1), PDMS (Polydimethylsiloxane) was used in 10 papers [4][5][6][7][8][9][10][11][12][13], making it the most used material for microfluidic devices. PMMA (poly(methyl methacrylate)) and polycarbonate materials were each used in 2 papers [6,7,9,14], and following them, various other materials such as PEEK (polyetheretherketone) [15], UV resin [15], PET (polyethylene terephthalate) [9], GelMa (gelatin methacryloyl) [16], ECM gel [5], agarose [17] and polystyrene [18] were used in one paper each.…”