Microfluidics at Fiber Tip for Nanoliter Delivery and Sampling

Abstract

Delivery and sampling nanoliter volumes of liquid can benefit new invasive surgical procedures. However, the dead volume and difficulty in generating constant pressure flow limits the use of small tubes such as capillaries. This work demonstrates sub-millimeter microfluidic chips assembled directly on the tip of a bundle of two hydrophobic coated 100 µm capillaries to deliver nanoliter droplets in liquid environments. Droplets are created in a specially designed nanopipette and propelled by gas through the capillary to the microfluidic chip where a passive valve mechanism separates liquid from gas, allowing their delivery. By adjusting the driving pressure and microfluidic geometry, both partial and full delivery of 10 nanoliter droplets with 0.4 nanoliter maximum error, as well as sampling from the environment are demonstrated. This system will enable drug delivery and sampling with minimally invasive probes, facilitating continuous liquid biopsy for disease monitoring and in vivo drug screening.

3D‐Printed Microinjection Needle Arrays via a Hybrid DLP‐Direct Laser Writing Strategy

“…DLP 3D printing is a vat photopolymerization approach in which a DLP projector is used to UV-crosslink a liquid-phase photocurable material in designated locations in a layer-by-layer manner to ultimately produce 3D objects composed of cured photomaterial. [62] Here, we leveraged DLP 3D printing to fabricate batches of arrayed capillaries in a single print run to overcome several drawbacks of recent esDLW approaches for printing 3D micro/nanostructured objects onto mesoscale fluidic components, such as micropiston-based microgrippers [63] and liquid biopsy systems [64] onto fluidic capillaries. First, the geometric control afforded by DLP 3D printing allows for each capillary to be designed with a variable OD to match the dimensions of the capillary base to those of the desired injector system.…”

“…This capillary-specific geometric customization capability obviates the need for additional fluidic adapters and/or sealants (e.g., glues) often required to couple the mesoscale capillaries to macroscale fluidic equipment (e.g., injector systems). [63][64][65] Second, the outer dimensions of the batch array can be designed to support facile loading into the DLW 3D printer, which eliminates the time, labor, and costs associated with manufacturing and employing custom-built capillary holders typically needed for esDLW approaches. [63][64][65] Lastly, the ability to print all of the capillaries in predefined array locations-with uniform surface positions and rotational orientations-addresses critical deficits associated with the use of custom-built capillary holders that rely on undesired manual (e.g., by hand and/or eye) alignment protocols for each individual capillary.…”

Microfluidic Surgery in Single Cells and Multicellular Systems

“…The cutting edge should be as sharp as possible to increase the stress at the edge and reduce the required cutting force, which yields higher quality, cleaner cuts. , Conventional surgical blades have blade tip widths on the order of 100 nm . This degree of sharpness can be fabricated using standard micro- or nanofabrication techniques, soft lithography, or high resolution 3D printing. , …”

“…47 This degree of sharpness can be fabricated using standard micro-or nanofabrication techniques, soft lithography, 48 or high resolution 3D printing. 49,50 Another consideration is the stiffness of the cutting tool. Stiffer materials are preferred, as they deform and break less easily and cut more efficiently.…”

Microfluidic Surgery in Single Cells and Multicellular Systems

“…46 This degree of sharpness can be fabricated using standard micro or nanofabrication techniques, soft lithography, 47 or high-resolution 3D printing. 48,49 Another consideration is the stiffness of the cutting tool. Stiffer materials are preferred, as they deform and break less easily and cut more efficiently.…”