Week 3 HW: Lab Automation

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๐Ÿค– Week 3 Homework: Lab Automation

Find and describe a published paper utilizing automation for novel biological applications; describe automation tools for your final project.

๐Ÿ“‹ Overview

     โ•”โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•—
     โ•‘  ๐Ÿค– LAB AUTOMATION: PAPER + PROJECT ๐Ÿค–                         โ•‘
     โ•‘                                                               โ•‘
     โ•‘   Part 1                    Part 2                            โ•‘
     โ•‘      โ”‚                         โ”‚                              โ•‘
     โ•‘      โ–ผ                         โ–ผ                              โ•‘
     โ•‘   [Microfluidics]          [gumol + new-Clara]                 โ•‘
     โ•‘   Synthetic cells          MD โ†’ oxidative surrogate            โ•‘
     โ•‘   (automation tool)        (validation pipeline)               โ•‘
     โ•šโ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•

This week covers:

  • Part 1: Published paper โ€” synthetic cells via droplet-based microfluidics
  • Part 2: Automation project description โ€” gumol + ECSOD/MSC + new-Clara validation pipeline

Part 1: Published Paper โ€” Automation for Novel Biological Applications

Paper Citation

Title: Synthetic cells and droplet-based microfluidics (review)
Journal: Small
DOI: 10.1002/smll.202400086
Year: 2024

Abstract Summary

Synthetic cells function as biological mimics of natural cells by mimicking salient features such as metabolism, response to stimuli, gene expression, direct metabolism, and high stability. Droplet-based microfluidic technology presents the opportunity for encapsulating biological functional components in uni-lamellar liposome or polymer droplets. Verified by its success in the fabrication of synthetic cells, microfluidic technology is widely replacing conventional labor-intensive, expensive, and sophisticated techniques justified by its ability to miniaturize and perform batch production operations.

Automation Tool

Droplet-based microfluidics โ€” lab-on-chip systems that automate encapsulation, mixing, and batch production of synthetic cell constructs. Microfluidics serves as the automation platform: it replaces manual, labor-intensive methods with reproducible, tunable, high-throughput workflows.

    DROPLET MICROFLUIDICS: MANUAL โ†’ AUTOMATED
    
    Before (manual):              After (microfluidic):
    
      ๐Ÿงช Hand pipetting             โ•ญโ”€โ”€โ”€โ”€โ”€โ•ฎ  โ•ญโ”€โ”€โ”€โ”€โ”€โ•ฎ  โ•ญโ”€โ”€โ”€โ”€โ”€โ•ฎ
      tedious, variable             โ”‚ โ—‹ โ—‹ โ”‚  โ”‚ โ—‹ โ—‹ โ”‚  โ”‚ โ—‹ โ—‹ โ”‚  โ† droplets
      batch-to-batch                โ•ฐโ”€โ”€โ”ฌโ”€โ”€โ•ฏ  โ•ฐโ”€โ”€โ”ฌโ”€โ”€โ•ฏ  โ•ฐโ”€โ”€โ”ฌโ”€โ”€โ•ฏ
                                       โ”‚        โ”‚        โ”‚
      "Labor-intensive"                โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”ผโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜
                                               โ”‚
                                               โ–ผ
                                        โ”Œโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”
                                        โ”‚  CHIP       โ”‚  โ† reproducible
                                        โ”‚  (automated)โ”‚     tunable
                                        โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜     batch production

Biological Applications

Synthetic Cell TypeDescription
Lipid vesicles (liposomes)Uni-lamellar lipid bilayers encapsulating biological components
Polymer vesicles (polymersomes)Polymer-based membranes for encapsulation
Coacervate microdropletsLiquid-liquid phase separation compartments
ColloidosomesColloidal particle-stabilized droplets

The review discusses microfluidic chip design for synthetic cell preparation, the combination of microfluidics with bottom-up synthetic biology for reproductive and tunable construction, and advances in biosensors and biomedical applications.

Novel Aspects

  • Reproducible, tunable construction โ€” Batch production from simple structures to higher hierarchical structures
  • Miniaturization โ€” Replaces conventional expensive techniques
  • Integration โ€” Design, assembly, manipulation, and analysis within lab-on-chip devices
  • Biomedical relevance โ€” Biosensors, drug delivery, therapeutic applications

Why This Paper Fits the Assignment

Microfluidics is an automation tool that achieves novel biological applications: it automates the fabrication of synthetic cells at scale, enabling research that would otherwise be labor-intensive and costly. The paper provides an overview of how this automation enables bottom-up synthetic biology and biomedical innovation.

    โ•”โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•—
    โ•‘  SYNTHETIC CELLS: MICROFLUIDICS AS AUTOMATION                 โ•‘
    โ•‘                                                               โ•‘
    โ•‘   [Droplet microfluidics]  โ”€โ”€โ–บ  Liposome | Polymersome |      โ•‘
    โ•‘   (automation tool)              Coacervate | Colloidosome     โ•‘
    โ•‘                    โ”‚                      โ”‚                    โ•‘
    โ•‘                    โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜                    โ•‘
    โ•‘                               โ”‚                               โ•‘
    โ•‘                               โ–ผ                               โ•‘
    โ•‘              Biosensors & biomedical applications             โ•‘
    โ•šโ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•

Part 2: Automation Tools for Final Project โ€” gumol + ECSOD + new-Clara

Project Overview

Project in development: A combined computationalโ€“experimental pipeline to study ECSOD (extracellular superoxide dismutase) overexpression from mesenchymal stem cells (MSCs) in acute radiation environments, with microfluidic validation serving as a surrogate for radiation exposure.

     โ•”โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•—
     โ•‘  ๐Ÿ”ฌ GUMOL + ECSOD + new-Clara PIPELINE ๐Ÿ”ฌ                     โ•‘
     โ•‘                                                               โ•‘
     โ•‘   Rust MD engine          Microfluidic validation             โ•‘
     โ•‘   (radiation sim)         (oxidative surrogate)               โ•‘
     โ•‘        โ”‚                           โ”‚                          โ•‘
     โ•‘        โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”ฌโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜                          โ•‘
     โ•‘                    โ–ผ                                          โ•‘
     โ•‘            ECSOD from MSC  โ”€โ”€โ–บ  Correlation & validation      โ•‘
     โ•šโ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•

Pipeline Components

ComponentRole
gumolCustom MD simulation engine in Rust for molecular dynamics in acute radiation environments
ECSOD / MSCSimulated overexpression of extracellular superoxide dismutase from MSC cells (mechanism still being refined)
new-ClaraMicrofluidic system for controlled validation runs
Surrogate modelMicrofluidic oxidative stress used as a surrogate for radioactive conditions

Workflow: Simulation โ†’ Validation โ†’ Correlation

โ”Œโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”
โ”‚  COMPUTATIONAL ARM                    โ”‚  EXPERIMENTAL ARM (AUTOMATION)       โ”‚
โ”‚                                       โ”‚                                       โ”‚
โ”‚  gumol (Rust MD engine)               โ”‚  new-Clara microfluidic system        โ”‚
โ”‚       โ”‚                                โ”‚       โ”‚                               โ”‚
โ”‚       โ–ผ                                โ”‚       โ–ผ                               โ”‚
โ”‚  Acute radiation environment          โ”‚  Simulated oxidative environment      โ”‚
โ”‚  simulations                          โ”‚  (surrogate for radiation)            โ”‚
โ”‚       โ”‚                                โ”‚       โ”‚                               โ”‚
โ”‚       โ–ผ                                โ”‚       โ–ผ                               โ”‚
โ”‚  ECSOD overexpression from MSC      โ”‚  Validation runs: controlled           โ”‚
โ”‚  (mechanism in refinement)            โ”‚  oxidative stress delivery            โ”‚
โ”‚       โ”‚                                โ”‚       โ”‚                               โ”‚
โ”‚       โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”ผโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜                               โ”‚
โ”‚                                        โ–ผ                                       โ”‚
โ”‚                              CORRELATION & VALIDATION                          โ”‚
โ”‚                              (MD predictions โ†” microfluidic data)              โ”‚
โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜

Automation Tool: new-Clara Microfluidic System

new-Clara is the primary automation tool in this project. It provides:

  • Controlled oxidative stress โ€” Reproducible delivery of oxidative conditions as a surrogate for radiation
  • Precision and throughput โ€” Automated, repeatable runs instead of manual handling
  • Data alignment โ€” Outputs that can be directly compared with gumol MD results

Because radiation experiments are costly and regulated, the microfluidic oxidative environment acts as a surrogate for acute radiation, enabling validation of computational predictions under safer, more accessible conditions.

    SURROGATE VALIDATION: Radiation โ†” Oxidative stress
    
    Radiation (expensive, regulated)     Oxidative stress (accessible)
              โ”‚                                    โ”‚
              โ”‚    "Same downstream damage         โ”‚
              โ”‚     pathways (ROS, etc.)"          โ”‚
              โ”‚                                    โ”‚
              โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”ฌโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜
                             โ”‚
                             โ–ผ
                    โ”Œโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”
                    โ”‚  new-Clara      โ”‚  โ† controlled, reproducible
                    โ”‚  microfluidic   โ”‚     surrogate runs
                    โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜

What Will Be Automated

  1. Microfluidic runs โ€” new-Clara controls flow, dosing, and timing of oxidative stress
  2. Data collection โ€” Automated or semi-automated readouts (e.g., fluorescence, viability) for correlation with MD
  3. Parameter sweeps โ€” Systematic variation of oxidative stress levels to map doseโ€“response and compare with simulation

Connection to Part 1 (Synthetic Cells Paper)

The synthetic cells / droplet microfluidics review supports this project by demonstrating how microfluidics enables:

  • Reproducible, tunable conditions โ€” Aligned with the need for controlled oxidative stress
  • Lab-on-chip workflows โ€” Similar to new-Clara’s role in validation
  • Biosensor and biomedical applications โ€” Relevant to ECSOD and MSC-based therapies for radiation injury

Current Status & Next Steps

  • gumol โ€” MD engine in Rust, in development
  • ECSOD/MSC mechanism โ€” Still being refined
  • new-Clara โ€” Microfluidic system for validation runs
  • Surrogate design โ€” Oxidative stress protocol as radiation surrogate

Example Pseudocode (Conceptual)

# Pseudocode: new-Clara validation run aligned with gumol MD output
# Input: MD simulation predicts ECSOD protection at oxidative stress level X
# Output: Microfluidic validation at equivalent oxidative dose

def run_validation(md_stress_level, n_replicates=3):
    """
    Map MD-predicted stress to microfluidic oxidative surrogate.
    Run n_replicates for statistical correlation.
    """
    oxidative_dose = map_md_to_oxidative_surrogate(md_stress_level)
    
    for rep in range(n_replicates):
        new_clara.set_oxidative_conditions(oxidative_dose)
        new_clara.run_flow_protocol()
        data = new_clara.collect_readouts()  # e.g., viability, ROS markers
        log_for_correlation(md_stress_level, oxidative_dose, data)
    
    return correlate_with_md_predictions()

Summary

    โ•”โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•—
    โ•‘  WEEK 3 HOMEWORK SUMMARY                                      โ•‘
    โ•‘                                                               โ•‘
    โ•‘   Part 1: Paper                                               โ•‘
    โ•‘   โ”Œโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”    โ•‘
    โ•‘   โ”‚ Microfluidics โ†’ synthetic cells (liposomes, etc.)     โ”‚    โ•‘
    โ•‘   โ”‚ Automation for reproducible, tunable fabrication    โ”‚    โ•‘
    โ•‘   โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜    โ•‘
    โ•‘                                                               โ•‘
    โ•‘   Part 2: Project                                             โ•‘
    โ•‘   โ”Œโ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”    โ•‘
    โ•‘   โ”‚ gumol (MD) โ”€โ”€โ–บ new-Clara (microfluidic) โ”€โ”€โ–บ validate โ”‚    โ•‘
    โ•‘   โ”‚ Oxidative surrogate for radiation; ECSOD/MSC focus    โ”‚    โ•‘
    โ•‘   โ””โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”€โ”˜    โ•‘
    โ•šโ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•โ•
PartContent
Part 1Synthetic cells via droplet microfluidics โ€” microfluidics as automation for reproducible, tunable biological fabrication
Part 2gumol (Rust MD) + ECSOD/MSC + new-Clara microfluidic validation โ€” oxidative surrogate for radiation, MDโ€“experiment correlation

This homework does not need to be tested on the Opentrons yet; it describes the intended automation workflow for the final project.