Quantitative Chemical Imaging of Nonplanar Microfluidics

Abstract

Confocal and multiphoton optical imaging techniques have been powerful tools for evaluating the performance of and monitoring experiments within microfluidic devices, but this application suffers from two pitfalls. The first is that obtaining the necessary imaging contrast often requires the introduction of an optical label which can potentially change the behavior of the system. The emerging analytical technique stimulated Raman scattering (SRS) microscopy promises a solution, as it can rapidly measure 3D concentration maps based on vibrational spectra, label-free; however, when using any optical imaging technique, including SRS, there is an additional problem of optical aberration due to refractive index mismatch between the fluid and the device walls. New approaches such as 3D printing are extending the range of materials from which microfluidic devices can be fabricated; thus, the problem of aberration can be obviated simply by selecting a chip material that matches the refractive index of the desired fluid. To demonstrate complete chemical imaging of a geometrically complex device, we first use sacrificial molding of a freeform 3D printed template to create a round-channel, 3D helical micromixer in a low-refractive-index polymer. We then use SRS to image the mixing of aqueous glucose and salt solutions throughout the entire helix volume. This fabrication approach enables truly nonperturbative 3D chemical imaging with low aberration, and the concentration profiles measured within the device agree closely with numerical simulations.

Freeform Assembly Planning

“…This can be used to make, for example, 3D microfluidic devices in materials with tunable optical properties. 35 A similar approach could be used to create woven or interpenetrating channel networks in structural polymers, enabling efficient delivery of 2-part healing chemistries to cracks. 36,37 The ability to incorporate 3D microchannel networks in elastomeric polymers also suggests applications in integrated microfluidics and soft robotics.…”

“…The isomalt was printed using a custom printer as described previously, 20,35 using a 110 µm nozzle (Subrex). About 10 g of isomalt was loaded into the extruder barrel and covered with a layer of pump oil.…”

“…[4][5][6] If the extruded material can be made to rapidly stiffen after extrusion, a supporting reservoir may be unnecessary, and the material can be deposited in free space. Stiffening mechanisms include UVinduced polymerization, 7,8 thermally induced polymerization, 9 solvent evaporation, 10 shear-thinning, 11 laser sintering, 12 and, in the case of thermoplastics, [13][14][15][16][17] metals, 18 and glasses, [19][20][21] cooling below the melting or glass transition temperature. Freeform patterning, layer-by-layer patterning, and patterning directly onto a flat or curved surface have been broadly termed direct-write assembly in the scientific literature.…”

Controlled dissolution of freeform 3D printed carbohydrate glass scaffolds in hydrogels using a hydrophobic spray coating

“…Raman spectra were collected for the isomalt, Kolliphor P188, and octadecane using a Horiba LabRAM HR confocal Raman microscope (Horiba Scientific, Edison, NJ). Octadecane tube surfaces coated with variable numbers of oscillations were imaged for thickness and surface roughness using a home built Stimulated Raman Scattering microscope, [16,29] which allowed for label free, high resolution chemical imaging of the cast structures. SRS images were collected at 2847 cm −1 , the CH 2 symmetric stretching vibration, to identify octadecane due to its strong and unique Raman cross section.…”

“…For example, Gelber et al extended the capabilities of sugar alcohol printing by combining the material properties of carbohydrate glass with a purpose built 3D isomalt printer that enabled the generation of intricate free-form structures. [14] Monolithic casting in polymers showed promise for microfluidic applications including as a dilution generator and a helical mixer, [15,16] but such complex molds have not yet been translated into hydrogels. Approaches such as dip coating or airbrush applications of coatings are enticing due to the ease of use, but manual control limits reproducibility and requires the development of user expertise.…”