Three dimensional microfluidics with embedded microball lenses for parallel and high throughput multicolor fluorescence detection

Abstract

We report a 3D microfluidic device with 32 detection channels and 64 sheath flow channels and embedded microball lens array for high throughput multicolor fluorescence detection. A throughput of 358 400 cells/s has been accomplished. This device is realized by utilizing solid immersion micro ball lens arrays for high sensitivity and parallel fluorescence detection. High refractive index micro ball lenses (n = 2.1) are embedded underneath PDMS channels close to cell detection zones in channels. This design permits patterning high N.A. micro ball lenses in a compact fashion for parallel fluorescence detection on a small footprint device. This device also utilizes 3D microfluidic fabrication to address fluid routing issues in two-dimensional parallel sheath focusing and allows simultaneous pumping of 32 sample channels and 64 sheath flow channels with only two inlets.

Basics of Micro/Nano Fluidics and Biology

“…Integrated fiber optics (or optical waveguides) may also improve the spatial resolution but it is limited by focusing issue at the blunt end of the fiber if there is no special ending [95][96][97]. Integrating spherical lenses to benefit from photonic nanojet is effective [98,99]. However these integrations require major changes in the process of fabrication of the chip.…”

The intersection of flow cytometry with microfluidics and microfabrication

“…To that end technologies that faithfully reproduce the flow cytometry analytical volume are of interest. One microfabricated approach that can be applied over many parallel channels is the use of a microball lens array, which has been shown to enable sensitive collection over many flow channels and provides a tight analytical volume for each analysed stream 150 . This or similar approaches may be highly effective for high throughput flow cytometers.…”

Cell sorting actuated by a microfluidic inertial vortex

“…However, arranged as a 4 × 4 array on chip, the pitch must be ≤1 mm to achieve sufficient sensitivity with reasonable optical components (lenses and filters ≤2 inch diameter). While several parallel flow cytometers [23][24][25][26][27][28][29] and one parallel sorter 30 have been published, until now no microfluidic cell sorters meet this specification, because of their size (including actuators and side-channels), low sort rates, or other complexities.…”