Isolating microfluidic structures and trapping bubbles
Inventors
Breinlinger, Keith Joseph • Hobbs, Eric D. • Liepmann, Dorian • Nevill, Joshua Tanner • White, Mark P. • Loureiro, Maria Jimena
Assignees
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Publication Number
US-12162006-B2
Publication Date
2024-12-10
Expiration Date
Abstract
Some configurations of a microfluidic apparatus can comprise a fluidic circuit of interconnected fluidic structures into which a plurality of different media can be introduced or extracted. A variety of operations can be performed with the different media including isolating with a second medium one or more of the fluidic structures that is filled partially or fully with a first medium. Discrete volumes of a medium can be moved through the isolating second medium to deliver materials or micro-objects to or remove micro-objects or materials from a fluidic structure that is otherwise isolated by the second medium. Some configurations of a microfluidic apparatus can isolate microfluidic structures in a microfluidic apparatus using flow rates or blocking structures, and some configurations can manage bubbles in fluidic structures.
Core Innovation
The disclosure provides microfluidic apparatuses for isolating adjacent isolation pens in a flow region. The microfluidic apparatus includes a fluidic channel with a size Wc and at least two isolation pens, where each isolation pen has a single opening with a size Wo to the fluidic channel and a connector region fluidically connecting the isolation pen to the fluidic channel. The relationship between Wc and Wo is configured to reduce exchange of soluble components from a first isolation pen into a second isolation pen while flowing a first fluidic medium along the fluidic channel.
The isolation is achieved by configuring the fluidic channel to be larger than the isolation pen openings, thereby reducing exchange of soluble components between isolation pens. Additional isolation approaches described include reduced diffusion via geometry and flow discontinuities, using serpentine or lengthened flow paths with minor branching gaps and configuring the use of an immiscible second fluidic medium to displace the first fluidic medium. The disclosure also includes flow-rate-based isolation, with optional getters to capture diffusing soluble materials.
The disclosure further addresses bubble management using bubble traps and trap chambers. Bubble trap openings are configured to be larger than the main-channel cross-sections to drive bubbles into a trap chamber, with variants that include dual openings and upstream placement to prevent bubbles reaching cell pens. The documented examples include selective pen isolation with immiscible fluids and bubble trapping, and capturing of secreted antibody near pen entrances using CD45-coated beads.
Claims Coverage
The partial content includes two independent claims (clm-00001 and clm-00028). Both independent claims share the same core configuration: a microfluidic apparatus with a fluidic channel and at least two isolation pens where Wc is larger than Wo to reduce exchange of soluble components.
Channel size larger than isolation pen opening size for reduced soluble exchange
In a microfluidic apparatus with a flow region comprising a fluidic channel of size Wc and at least two isolation pens each having a single opening of size Wo to the fluidic channel, the size Wc of the fluidic channel is larger than the size Wo of the opening to each isolation pen, and the relationship between Wc and Wo is configured to reduce exchange of soluble components from a first isolation pen into a second isolation pen.
Operating process: flowing first fluid, disposing micro-object, and isolating pens
Operating the microfluidic apparatus includes flowing a first fluidic medium along the fluidic channel, disposing a first biological micro-object in a first isolation pen of the at least two isolation pens, and fluidically isolating the first isolation pen from a second isolation pen of the at least two isolation pens while the reduced exchange configuration is maintained.
Connector region fluidically connecting isolation pen to the channel
Each isolation pen has a single opening and a connector region fluidically connecting the isolation pen to the fluidic channel, where the connector region comprises the single opening and fluidically connects the isolation region to the fluidic channel, with Wc larger than Wo so the relationship is configured to reduce exchange of soluble components between isolation pens.
Across both independent claims, the inventive coverage centers on using a microfluidic channel whose size is larger than the single-opening size of isolation pens to reduce exchange of soluble components, combined with operating steps that flow a first fluid, dispose a biological micro-object in a selected pen, and fluidically isolate the selected pen from an adjacent pen.
Stated Advantages
Reducing exchange of soluble components from a first isolation pen into a second isolation pen.
Documented Applications
Selective isolation of adjacent isolation pens by flowing immiscible fluids, together with bubble trapping to prevent bubbles reaching cell pens.
Capturing secreted antibody near pen entrances by using CD45-coated beads to capture secreted antibody and limit diffusion into the channel.
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