Acoustofluidics technology can be used to trap live cells (and also micro/nanoparticles) in microenvironments suitable for cell assays. Herein, a cheap and easyto-fabricate device is proposed that works with Raman spectroscopy for biosensing applications. The device comprises a 3D-printed microchamber working as a halfwavelength acoustic resonator. By tuning the resonance frequency with a low voltage (%4 V), cells or particles are aggregated and levitated in seconds by the action of the acoustic radiation force. Based on finite element simulations, the radiation force field produced inside the device is described. In the cellular enrichment (aggregation) process, a metastable honeycomb lattice is formed mostly due to the cell-to-cell attraction caused by the secondary acoustic radiation force. Orderly and metastable levitating aggregates provide an excellent arrangement for Raman spectroscopy to investigate cells individually. Polystyrene particles are used for the device characterization and Raman acquisition process. Biosensing applications are showcased with live murine macrophages J774.A1, which are used in infection assay of leishmaniasis disease. The unique features of the device, e.g., simple fabrication process with cheap materials, simple operation, fast time response, and formation of metastable cellular aggregates; hold a noteworthy potential for applications in life sciences and biotechnology involving cell assays.
Acoustofluidics is a technique that utilizes the forces produced by ultrasonic waves and fluid flows to manipulate cells or nano-/microparticles within microfluidic systems. In this study, we demonstrate the feasibility of performing the Raman analysis of living human erythrocytes (Erys) within a 3D-printed acoustofluidic device designed as a half-wavelength multilayer resonator. Experiments show that a stable and orderly Ery aggregate can be formed in the pressure nodal plane at the resonator's mid-height. This has a significant potential for improving the applicability of Raman spectroscopy in single Ery analysis, as evidenced by the acquisition of the spectrum of healthy and pre-heated Erys without substrate interference. Moreover, principal component analysis applied on the obtained spectra confirms the correct Ery group identification. Our study demonstrates that 3D-printed acoustofluidic devices can improve the accuracy and sensitivity of Raman spectroscopy in blood investigations, with potential clinical applications for noninvasive disease diagnosis and treatment monitoring.
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