Modeling of Microfluidic Systems for High Throughput Cell Culture


This portfolio of microfluidic technologies improves cell culture techniques. Current cell culture techniques have several limitations: they are resource and process intensive, the culture environment is inconsistent, and manual manipulation is both time consuming and error prone.

These microfluidic inventions enable more consistent cell culture environments; allow use of high throughput devices which provide speed and consistency; conserve cell-cell factors to maintain cell-cell communication; and ultimately reduce operator error.

High Throughput In Vitro Fertilization (IVF) Device compatible with Multi-Head Flow Cytometry Systems

This invention consists of microchannels to incubate oocytes and embryos. Microchannels are aligned to match the multi-head pipettor of a fluid handling robot with the dispenser of flow cytometers. After a certain amount of incubation time, depending on species, sorted sperm are introduced into the microchannels using a flow cytometer. The microchannels direct the movement and location of the sperm toward the oocyte. Once fertilized, embryos are removed from the fluid handling root and are ready for downstream steps. This process is very low shear, can be easily scaled for high throughput and should improve the yield of current processes.

High Throughput Migration Device for Chemotaxis Studies

Most chemotaxis devices cannot be used in high throughput studies. The geometry and surface tension properties of this invention use fluidic resistance to provide convection and a flow barrier, which then enable the development of concentration gradients. Fluidic resistance ensures this gradient is not disturbed, preserving cell-cell factors. The chamber has a cell inlet, a chemoattractant is introduced in the source channel, and a blank medium is introduced in the sink channel.

Microfluidics Well Insert (MWI) for Oocyte/Embryo Culture

To facilitate culture microenvironments for embryos similar to in-vivo, this invention provides a ready-to-use culture system made using soft lithography technology. This invention has two versions: channel-less and channeled. The channel-less version is composed of wells of a size especially tailored for the characteristic size of the particular species of oocyte/embryo being cultured. This allows for a flexible platform that will accommodate a wide variety of animal species. The channeled version has microchannels networked between the wells of the channel-less version, so that cell-cell communication between oocytes/embryos can be maintained during medium change. This invention is particularly useful for culturing zona pellucida-free oocytes and embryos as the well holds the cells together much as the zona pellicuda would with intact oocytes or embryos. This invention is easily scalable and fits into standard culture dishes.

Automatic Top-Off System using a Surface Tension-Based Valve

This liquid handling system automatically fills culture wells to desired levels without operator handling. Liquid is passively added as surface tension drops, maintaining the medium at a constant level without manual manipulation. This has the following benefits:

  • Scalable to high-throughput
  • Culture environment not disrupted
  • Risk of operator error reduced

Open-Close-Open-Close-Open (OCOCO) Microchannel System

Microchannels provide good micro-environments for cell/embryo/oocyte culture and chemical analysis. However microchannels are very inconvenient for loading or accessing samples. This invention uses passive pumping to change mediums or reagents. This invention does not use any connecting channels or tubing, thus eliminating waste. It can be easily expanded for high-throuhput. The figure shows the liquid flowing from small drop to large drop by surface energy forces.