Overview



Upon closer consideration of the need for more accessible and widely available diagnostic systems, we recognized the importance of a system that extended beyond the confines of traditional laboratories. The imperative of making laboratory-grade technology accessible to the general public became apparent. This is where lab-on-chip, or LOC, and the realm of microfluidics emerged as our chosen solution.

Our primary aim is to introduce an affordable and user-friendly diagnostic tool for Major Depressive Disorder (MDD) based on biomarkers. We achieved this by designing a microchip that can accomplish this task.

The process is straightforward: you simply introduce a specific volume of blood serum into the chip's inlet, use the provided pumps to push it through, and then wait for an incubation period to allow the quantifiers to mix with the blood serum.



Kinetics



The chemical theory of kinetics was employed to analyze our reactions. These reactions were assumed to act like single molecular reactions rather than multi-molecular ones. It was found that our results matched with the wet-lab data we had gathered. Two different reactions were considered. One involved the addition of aptamer to the cDNA molecule, while the other concerned the aptasensor (aptamer + cDNA) and its interaction with the target biomarker.



Microfluidics Chip Design



Our microfluidic chip design process was a meticulous journey, driven by extensive research and data analysis. Several key steps and considerations guided our design:

  • Literature Review:
  • We conducted a comprehensive review of research papers that shared similar principles, serving as foundational inspiration for our design.

  • Textbook Insights:
  • Our team delved into microfluidics and fluid mechanics textbooks to derive the essential parameters required for our chip's design.

  • Simulations:
  • To validate our calculations, we performed simulations, ensuring the accuracy of our design.

  • Expert Consultations:
  • We sought the guidance of multiple professors and experienced engineers to verify the construction and functionality of our microfluidic chip.



    Basic principles of working



    Some basic mathematical principles we kept in mind while designing the chip were:

  • Law of Fluid Transport
  • Navier-Stokes Equation
  • Reynold’s Number
  • Scaling Laws

  • Laws of Fluid Transport

  • Continuity Equation:
  • This equation represents the principle of mass conservation in fluid dynamics. It states that the mass flow rate into a control volume must equal the mass flow rate out. In mathematical terms, it can be expressed as:



    Where:

  • ∇· represents the divergence operator.
  • ρ is the fluid density.
  • 𝑢 is the fluid velocity vector.
  • Bernoulli's Equation:
  • Bernoulli's equation describes the relationship between pressure, velocity, and elevation in a flowing fluid. It is a statement of the conservation of energy along a streamline and is particularly useful for understanding fluid flow in pipes or over objects. The equation is as follows:



    Where:

  • P is the fluid pressure.
  • ρ is the fluid density.
  • u is the fluid velocity.
  • g is the acceleration due to gravity.
  • z is the height above a reference point.
  • Navier-Stokes Equations

    These equations describe the motion of fluid substances and are fundamental in fluid dynamics. The Navier-Stokes equations take into account the conservation of momentum and are written as a system of partial differential equations. They can be quite complex and are used to analyze and predict fluid flow in various situations.

    Reynolds Number

    The Reynolds number is a dimensionless quantity used to predict the flow regime of a fluid. It is a ratio of inertial forces to viscous forces and helps determine whether the flow is laminar or turbulent. The formula for Reynolds number is:



    Where:

  • Re is the Reynolds number.
  • ρ is the fluid density.
  • u is the fluid velocity.
  • L is a characteristic length.
  • μ is the dynamic viscosity of the fluid.
  • These principles and equations govern the behavior of fluids and are essential for understanding fluid transport in various engineering and scientific applications. While there isn't a specific "Law of Fluid Transport," these principles collectively describe how fluids move and are transported in different systems.



    Material Analysis



    Selecting the appropriate material for our microfluidic chip was a crucial decision. To ensure compatibility with our reagents and desired reactions, we conducted a thorough material analysis. The choice ultimately boiled down to hydrophilicity versus hydrophobicity:

  • We opted for a hydrophilic material due to the water-based nature of our solutions, such as blood serum, enabling unhindered material flow.
  • This choice also facilitated the creation of a capillary-based microfluidics device. Thus, we settled on using Polydimethylsiloxane (PDMS), a hydrophilic polymer with minimal cohesive forces, making it an ideal choice for our capillary-based device.


  • Design-Build-Test-Learn (DBTL)



    Our design process involved multiple iterations and two distinct phases, which followed a structured protocol:

  • Protocol Definition
  • Clearly outlining the protocol for execution on the microfluidic device.

  • Literature Review
  • Identifying relevant academic and industrial literature where microfluidic devices were used to address similar problems.

  • Overall Architecture:
  • Designing the microfluidic device's architectural layout.

  • Design Refinement:
  • Adjusting dimensions, channel features, and other parameters to optimize performance.

    First Phase:

    We initially developed a two-channeled chip to process different biomarkers (aptamers and nanoprobes). This design underwent three DBTL cycles, fine-tuning channel dimensions and flow characteristics.

    Second Phase:

    In the second phase, we designed a five-channel microfluidic device, involving five distinct DBTL cycles.



    Software Utilized



    To create the chip's design for printing, we utilized two software tools:

  • 3D UF: Recommended by a prior Boston University iGEM team from 2016 and 2017, this software streamlined the design process, offering pre-built libraries necessary for chip construction.
  • AutoCAD: This software was employed to transform the 3D UF designs into a printable format. The final files, converted using AutoCAD, were submitted to CCAMP.


  • References



  • Sanka, R., Lippai, J., Samarasekera, D. et al. 3DμF - Interactive Design Environment for Continuous Flow Microfluidic Devices. Sci Rep 9, 9166 (2019). //doi.org/10.1038/s41598-019-45623-z
  • Bruus, H., & Technical University of Denmark. Department of Micro and Nanotechnology. (2004). Theoretical Microfluidics.
  • Qin Wang Hao Zou Hailong Yao Senior Member, IEEE Tsung-Yi Ho Senior Member, IEEE Robert Wille Senior Member, IEEE Yici Cai Senior Member, IEEE. (n.d.). Chair for Design Automation. //www.cda.cit.tum.de/files/eda/2017_tcad_codesign_flow_control_layer_flow_based_biochips.pdf
  • Sammer-ul Hassan 1,2,* , Aamira Tariq 3 , Zobia Noreen 3 , Ahmed Donia 3 , Syed Z. J. Zaidi 4 , Habib Bokhari 3 and Xunli Zhang 1,2,*. (n.d.). National Center for Biotechnology Information. //www.ncbi.nlm.nih.gov/pmc/articles/PMC7459612/pdf/diagnostics-10-00509.pdf
  • Shaun Berry and Jakub Kedzierski. (n.d.). MIT Lincoln Laboratory. //www.ll.mit.edu/sites/default/files/page/doc/2019-02/17_2_4Berry.pdf
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