Team:BostonU HW/Applied Design

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Product Design

TERRA addresses the lack of accessibility of microfluidics to the synthetic biology community by automating the exportation of outputs of microfluidic experiments onto standard lab vessels, such as a 96-well plate. Currently, researchers can either manually collect these outputs and transfer them into plates for later analysis or invest in highly specialized equipment, such as embedded sensors, to run real time, on chip analysis.1 Manual collection disrupts the benefits of automated microfluidic experiments, and implementing sensors requires extensive knowledge which synthetic biologists typically do not have.2 Incorporating sensors and other analytical systems on microfluidic chips requires expertise of microelectronics and fluid dynamics, as well as time for characterization of the devices. TERRA is the accessible and automated solution to incorporate microfluidic technology into the experimental workflow for synthetic biologists.

The Problem and TERRA

Some of the reasons why microfluidic devices are currently inaccessible and not widely used in the field of synthetic biology are as follows:

  1. A lack of standardization across the microfluidic industry - differences in chip sizes, materials, and manufacturing methods

  2. Difficult to integrate sensors into microfluidic devices - requires knowledge of microelectronics and fluid dynamics as well as takes time to fully characterize the system

  3. Difficult to export the output of microfluidic devices in an organized manner - harder to integrate into other workflows

  4. A lack of standardization of synthetic biology protocols - different labs use variations of similar protocols making it harder to design microfluidic chips for a general synthetic biology protocol

  5. High entry costs to begin manufacturing microfluidic chips

TERRA addresses all of these limitations either directly or indirectly.

  1. TERRA is microfluidic agnostic - since TERRA was designed to be compatible with both self-designed and commercial microfluidic chips, TERRA treats the microfluidic chip of interest like a black box system. Through the TERRA Adapter, the user connects their chip of interest to TERRA to facilitate select and redirect outputs.

  2. TERRA is an automated system capable of selectively dispensing the output of a microfluidic chip into common lab vessels - as a system, TERRA consists of an active XY-plane and UI interface designed to accurately dispense the outputs of a microfluidic chip to a desired location on a laboratory vessel such as a 96 well plate. The ability to accurately dispense the output of the microfluidic chip enables effective integration of TERRA into the workflow of various synthetic biology procedures. Additionally, exporting onto standard laboratory vessels allows researchers to analyze the microfluidic outputs using benchtop equipment already in the lab, such as a plate reader or flow cytometer, reducing the need to incorporate sensors into microfluidic devices.

  3. Works in conjunction with the 2017 BostonU Hardware iGEM team’s project MARS - MARS designed a set of 9 standardized microfluidic chips capable of running 9 common synthetic biology lab protocols. Additionally, MARS created a series of videos and documentation, Microfluidics 101, designed to introduce people to the basic principles and workings of microfluidics. This helps bridge the knowledge gap as well as created microfluidic chips for standardized protocols.

  4. TERRA is application agnostic and cost effective - Since the project is microfluidic based, it has a variety of potential applications from liquid handling to PCR. Due to its DIY and open-sourced nature, TERRA is a low-cost solution, which further serves to increase its accessibility to the community.

TERRA and Other Potential Solutions

Another solution to the problem of microfluidic accessibility is outlined in the 2013 paper “Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations.” 3 In this paper, they described how to regulate the inputs and valves of a microfluidic chip using an Tecan EVO 200.

The primary advantage of this solution is that it is better equipped to deal with small volumes, working with pipettes on the scale of 25-5000 μL. 3 In addition to the larger stepping accuracy, this solution is more precise compared to TERRA. Rather than exporting the output of the microfluidic chip, the output is transported downstream to the analytics section where it can be analyzed by the plate reader built into the LHS. However, this method requires a researcher to purchase the necessary hardware which can cost $100,000 or more. 3 This makes it extremely challenging for synthetic biologists to incorporate this process into their workflow.

The two primary advantages that TERRA has over this system are flexibility and cost. TERRA costs less than $400 and is manufactured via accessible means such as 3D printing. TERRA accomplishes this low-cost price point by taking a DIY approach to automating microfluidic experiments. While the LHS system is more precise, TERRA is designed for researchers to perform a wider array microfluidic experiments. In terms of chip flexibility, TERRA can run a wider variety of both microfluidic experiments and types of microfluidic chips by way of the TERRA adapter. Therefore, chips with fabricated commercially as well as the MakerFluidics workflow can be integrated into TERRA. This increases the design space for microfluidic experiments for synthetic biologists.

TERRA’s largest flaw is the complexity of dispensing a wide variety of sample volumes. Currently, continuous flow microfluidics is the most compatible with our system. Using our current size tubing of (0.0625 inches or 1.6mm) , the average droplet dispensed is 48 μL, so volumes that are multiples of the average droplet size are easy to dispense. If the desired volume is smaller or in multiples of this designation, droplet-based microfluidics must be used to dispense that volume accurately. Through this method, the 48 μL droplet that dispensed from the nozzle is part sample and part mineral oil. The proportions of these liquids can be manipulated through flow rate and microfluidic chip design to achieve the desired volume.

Though our modeling experiments were able to discern that changing either the diameter or material of the tubing should also change the size of the droplet dispensed from the nozzle. Given more time, we would have provided TERRA with the functionality to allow the user would have greater control over their experiment by choosing certain nozzle tubing based on combinations of material and diameter. This type of control would be similar to selecting end mills or drill bits in machining.

Impacts of TERRA

A major impact of TERRA is how it both automates and incorporates microfluidics into pre-existing workflow of synthetic biology experiments . Once a microfluidic experiment is set up on TERRA and the UI, it can be left to run unattended, leaving the researcher free to work on other projects while the chip is running. This combined with the flexibility and wide range of microfluidic chips compatible with TERRA make the system easy to incorporate into different workflows.

Potential Users

Engaging with Experts and Potential Users

During the course of this project, we met with two commercial microfluidic companies based in the greater Boston area, Phenomyx and Fraunhofer Center of Manufacturing Innovation. During these meetings, we presented an overview of our system TERRA alongside the goals and motivations driving the project. Meeting with these microfluidic experts helped give us an idea about how to use our system to help remedy the lack of standardization in the field of microfluidic as well as brainstorm some potential applications and ways to integrate our system into some common workflows. Explore our integrated human practices page for more information.

In addition to the experts in the commercial microfluidics industry, we also consulted our resident microfluidic experts and other researchers here at Boston University’s Design Automation and Manufacturing Production (DAMP) Lab. From the researchers focused on biology, we were given a some protocols that TERRA should be able to run in order to improve their workflows. The graduate students who worked directly with microfluidics helped us determine the feasibility of some of these workflows and help guide the course of the project.