Microfluidic Fish Larvae Device for High-Throughput Antimicrobial Screening
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Solution Overview
Problem
Current microfluidics-based technologies lack a platform for studying vertebrate-microbe interactions, particularly for high-throughput screening of antimicrobials and personalized medicine applications, as they do not effectively translate benefits like small sample size and high-throughput screening to fish-microbe studies, which are crucial for understanding microbial interactions with fish as a suitable vertebrate model.
Innovation Solution
A microfluidic-based device with a multi-layered structure for establishing an in vivo wound infection model in fish, using Medaka fish as a host, which includes a base layer, an intermediate host-pathogen interface layer, and a bioassay layer to induce and assess pathogenic infections, allowing for the evaluation of drug candidates and antimicrobial efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional fish tanks or Petri dishes are used for fish-microbe studies, then the studies can be conducted with simple setup, but the sample size is large and high-throughput screening capabilities are not achieved
Solution Approach 1:
The device is divided into multiple independent channels (e.g., 96 channels) that can simultaneously accommodate individual fish larvae. Each channel functions as an independent micro-reactor, enabling parallel processing and high-throughput screening while maintaining simple operation protocols similar to conventional methods
Solution Approach 2:
The microfluidic system utilizes fluid flow through controlled channels to deliver pathogens, antibiotics, and nutrients to fish larvae in each channel. The hydraulic design enables automated high-throughput screening by circulating media through all channels simultaneously, replacing manual large-volume handling with precise micro-fluid control
2Adaptability or versatility
If microfluidic devices are used for zebrafish embryo studies, then small sample size and high-throughput screening are achieved, but no platform is available for vertebrate-microbe interaction studies
Solution Approach 1:
The device is designed as a universal platform that can accommodate various vertebrate models (fish larvae, embryos) and various pathogens (bacteria, fungi, viruses). The standardized channel design and modular multi-layer structure allow the same device to perform diverse experiments including wound infection models, systemic infections, and antibiotic efficacy testing across different pathogen-host combinations
Solution Approach 2:
The device employs a multi-layered structure where different functional layers are stacked and integrated. The base layer contains channel structures, intermediate layers provide structural support and additional functional channels, and top layers enable assay operations. This nested architecture consolidates multiple functions into a single integrated platform, making it adaptable to various vertebrate-microbe interaction studies
3Productivity
If conventional methods are used for antimicrobial screening, then the process is simple, but the screening throughput is low and time-consuming
Solution Approach 1:
The microfluidic system enables continuous circulation of pathogen suspensions and antibiotic solutions through all channels simultaneously. Media can be continuously refreshed, and multiple antibiotics can be sequentially or concurrently tested in different channels, maintaining continuous experimental progress rather than discrete batch processing, thereby dramatically increasing screening throughput and reducing total time required
Data Source
AI summary
The present invention provides an integrated microfluidic-based device for establishing a wound infection in vivo model suitable for high throughput bioassay such as potential drug screening, in vivo dosing optimization, host-microbe or microbe-microbe interactions under the influence of specific agents of interest, and studying regulatory mechanisms of certain inflammatory diseases relating to or arising from the wound infection. The present invention allows direct qualitative and quantitative assessments of specific markers expressed due to the wound infection by one or more microbes devoid of cell sorting, isolation, or labelling as in other conventional in vivo models or methods.