Clin Exp Otorhinolaryngol.  2021 Feb;14(1):29-42. 10.21053/ceo.2020.00626.

Prospects and Opportunities for Microsystems and Microfluidic Devices in the Field of Otorhinolaryngology

• Hwang SH
• Gonzalez-Suarez AM
• Stybayeva G
• Revzin A

• KMID: 2512879
• DOI: http://doi.org/10.21053/ceo.2020.00626

Abstract

Microfluidic systems can be used to control picoliter to microliter volumes in ways not possible with other methods of fluid handling. In recent years, the field of microfluidics has grown rapidly, with microfluidic devices offering possibilities to impact biology and medicine. Microfluidic devices populated with human cells have the potential to mimic the physiological functions of tissues and organs in a three-dimensional microenvironment and enable the study of mechanisms of human diseases, drug discovery and the practice of personalized medicine. In the field of otorhinolaryngology, various types of microfluidic systems have already been introduced to study organ physiology, diagnose diseases, and evaluate therapeutic efficacy. Therefore, microfluidic technologies can be implemented at all levels of otorhinolaryngology. This review is intended to promote understanding of microfluidic properties and introduce the recent literature on application of microfluidic-related devices in the field of otorhinolaryngology.

Keyword

Microfluidics; Organoids; In Vitro Diagnostics; Organ-on-a-Chip; Otolaryngology

Figure

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  Fig. 1. Characteristics of flow in microfluidic devices. Laminar flow (A) and diffusion (B) of molecules inside microchannels are demonstrated.

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  Fig. 2. Process of manufacturing a microfluidic device. A silicon wafer (A) is coated with photoresist (B) to transfer the design of a microfluidic device using standard photolithography techniques (C). The mold (D) is used as the frame to shape a polydimethylsiloxane (PDMS) mixture (E) and baked to harden it (F). Cured PDMS is cut (G) and peeled off from mold (H). After punching inlets and outlets (I), PDMS device and a glass substrate are treated with oxygen plasma (J) to bond both surfaces (K) and end up with the final microfluidic device (L).

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  Fig. 3. Schematic depicting mold fabrication by photolithography and polydimethylsiloxane (PDMS) replicas fabrication by soft lithography. A clean silicon wafer (A) is coated with photoresist (B) and microfluidic device design is transferred by ultraviolet (UV) exposure (C). Unexposed photoresist is removed using a developer (D) to end up with the final mold (E). A PDMS mixture is poured on top of the mold (F), baked at 80°C for 1 hour, to then peel off the device from the mold. PDMS device and a glass substrate are plasma treated (G) and bond together to obtain the final device (H).

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  Fig. 4. Schematic illustration of organoid models. Microfluidic devices containing patient-derived cells could be used to evaluate drug efficacy, eliminating the need for animal models and enabling the practice of personalized medicine.

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  Fig. 5. Schematic illustration of basophil activation. Resting basophils (A) release various immune modulators, such as histamine, and express CD63 and CD203c at the cell surface after activation (B) by cross-linking allergens and immunoglobulin E (IgE)-antibodies.

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  Fig. 6. Principles of basophil activation test in microfluidic devices. (A) The dye-loaded commercial basophils are sensitized using a patient's serum-specific immunoglobulin (Ig). After challenge with an allergen, the dye fluorescence is secreted from the basophils and analyzed in the detection chamber. (B) The microfluidic device captures basophils with anti-CD203c antibody and measures the level of CD63 expression in the captured allergen-exposed basophils.

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  Fig. 7. Microfluidic device to mimic the structure of nasal mucosa. (A) Nasal mucosa structure has three layers (epithelial layer, extracellular matrix, and vascular layer). (B) Each layer is imitated using an air–liquid channel, gel (collagen or Matrigel)-filled channel, and liquid-covered channel, respectively. ECM, cell-extracellular matrix; 3D, three-dimensional.

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  Fig. 8. Real-time monitoring of cilia beating frequency in microfluidic device. In vitro differentiated human nasal epithelial cells are incorporated into microfluidic chips for real-time monitoring of the cilia beating function. PDMS, polydimethylsiloxane.

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  Fig. 9. Schematic illustration of reciprocating system and sequential operation. The red pump indicates an actively working pump in each individual step (alphabetical order, A-E). The blue points near the cannula indicate the drug spread by diffusion. Light color changes represent the drug diluted by perilymph.

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  Fig. 10. Circulating biomarkers released from cancer tissue. Apoptotic cancer cells release biomarkers (circulating tumor cells [CTCs], circulating tumor DNA [ctDNA], and exosomal microRNA [miRNA]) into blood, whereas necrotic tumor cells shed biomarkers into saliva.

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  Fig. 11. Microfluidic chip design. Immune cells are loaded into Channel A, and cancer cells are place in Channel B. Channel C is used for hydration. The red rectangle magnifies the connections between channels, which are linked with microtubules.

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