In drug discovery, researchers need efficient and flexible systems that can handle compound screening workflows with precision while adapting to varying throughput demands. The Echo FlexCart system (Fig. 1) represents a breakthrough in acoustic dispensing technology, purpose-built for laboratories requiring rapid turnaround times in low to medium throughput compound screening.
Figure 1. HighRes Compound Screening Echo FlexCart System
Video 1. Demo video of the universal FlexCart.
Designed for Real-World Screening Challenges
The Echo FlexCart system (Fig. 1) addresses a critical need in pharmaceutical research: creating assay-ready plates quickly and accurately. Rather than running assays directly on the platform, the system excels at preparing assay-ready plates for downstream analysis, enabling laboratories to maintain flexible workflows while ensuring consistent, high-quality results.
The system's design centers around acoustic dispensing technology, utilizing the Echo 650T or 655T mounted on a turntable for optimal accessibility. Samples arrive in acoustic tubes, 96 tubes per rack, making them immediately compatible with the Echo's acoustic transfer capabilities. For laboratories with budget constraints or existing sample libraries, the system also supports Echo-compatible 384-well source plates as an alternative to tube-based formats. This plate-based approach eliminates the need for the tube decapper module, offering a more cost-effective entry point while maintaining the precision and walkaway automation advantages of acoustic dispensing.
The featured instruments in this system are:
- Dockable Custom FlexCart
- HighRes Biosolutions ACell 512 Robot
- Labcyte Echo 650T on turntable
- HighRes Biosolutions MicroSpin
- Azenta Automated Plate Peeler (formerly Brooks XPeel) on slide
- Brooks A4S on slide
- Gyger Certus Flex on slide
- HighRes Biosolutions PicoServe
- HighRes Biosolutions LidValet
- HighRes Biosolutions 1D Barcode Scanner
- HighRes Biosolutions PlateOrient
- HighRes Biosolutions 4-Position PlateHotel
- 3x HighRes Biosolutions Static Nests
- Agilent Plate Labeler
- LVL Acoustic Decapper
- Liconic STX44 BT (expansion)
- Revvity Victor Nivo (expansion)
Figure 2. HighRes Compound Screening Echo FlexCart System Design
Flexible Workflow Options for Every Laboratory
One of this system's standout features is its dual-protocol approach, offering laboratories the choice between fixed or variable volume workflows depending on their specific needs.
1. Fixed Protocol: The "Set It and Forget It" Approach
The fixed protocol option is ideal for laboratories running repetitive dose curves with consistent plate layouts (Fig. 3). This source-centric method uses predetermined pick lists that don't require plate barcodes—only well-to-well transfer instructions.
The workflow sequence:
- Compounds transfer from source tubes to intermediate plates
- Compounds transfer from source tubes to assay-ready plates (ARPs)
- Controls are added to ARPs
- Intermediate plate contents transfer to ARPs
This approach requires just one protocol in CellarioScheduler with multiple pick list files associated with it. The pick lists remain fixed and don't change between runs—they simply prescribe which wells transfer to which other wells. Once configured, the same transfers execute in the same order for every run, making it perfect for standardized screening campaigns.
Alternative sequencing: The fixed protocol can also be run destination-centric, processing each assay-ready plate completely (source → ARP, intermediate → ARP, controls → ARP) before moving to the next plate.
Figure 3. Protocol for Fixed Approach
Figure 4. Simulation of Fixed Approach, Sample View
Figure 5. Simulation of Fixed Approach, Resource View
2. Variable Protocol: Maximum Customization
For laboratories requiring enhanced source plate protection, the variable protocol can be implemented using a source-centric workflow architecture. While the destination-centric approach (as designed) is preferred by most users for its efficiency, some applications benefit from minimizing source plate exposure through a two-stage transfer process.
This alternative workflow utilizes two sequential protocols in CellarioScheduler:
- Protocol 1: Source to Intermediate Transfer – Prepares intermediate plates from source materials with minimal handling
- Protocol 2: Intermediate to Destination Assembly – Combines intermediate plates and controls to generate assay-ready plates
This source-centric design reduces the number of times valuable source plates must be accessed, extending their viability for subsequent experiments while maintaining the flexibility advantages of the variable protocol approach (Fig. 6).
Pick lists for this method include plate barcodes and prescribe complete plate-to-plate transfers. This means you can change which specific plates are used and modify transfer orders and volumes between runs. While this approach requires more upfront planning—and ideally integration with a LIMS system for pick list generation—it provides unmatched flexibility for varied screening campaigns.
Figure 6. Protocols for Variable Approach
Key difference: Unlike Option 1 where pick lists are reusable templates, Option 2 requires new pick lists for each order (even if just updating plate barcodes), but the transfer patterns can vary significantly between runs.
Figure 7. Simulation of Variable Approach, Sample View
Figure 8. Simulation of Variable Approach, Resource View
Table 1. Features of each workflow option for automating compound screening that one should consider.
|
Option 1 - Fixed |
Option 2 - Variable |
|
Very easy to run if doing the same dose curve and plate layout repeatedly |
Preferred option if transfers will vary |
|
One CellarioScheduler protocol |
Two CellarioScheduler protocols, can link/schedule them together |
|
Pick list files can be associated with the protocol and don’t need to be selected for each order |
New pick lists will be needed for each order, even if it’s just the rack/plate barcodes |
|
Pick lists only prescribe well-to-well transfers and do not include barcodes |
Pick lists prescribe plate-to-plate transfers and must include barcodes for source plates |
|
The same transfers will happen in the same order, based on plate number |
Transfers can be highly variable in different orders, if desired |
|
Order of operations is determined by the CellarioScheduler protocol |
Order of operations primarily is determined by the pick list |
|
Can have a small library of grouped lists that are tied to different protocols |
May need informatics support to dynamically generate pick lists |
|
Set it and forget it |
Attention needed to manage protocol variability |
Solving the Dilution Challenge
A key technical consideration in any compound screening workflow is achieving the correct final concentrations. The Echo system's minimum transfer volume of 2.5 nanoliters, while remarkably precise, isn't always small enough for certain dilutions. This is where intermediate plates become essential.
The workflow creates intermediate dilution plates by transferring small volumes of stock solution (as little as 2.5 nL) into larger diluent volumes (typically 30-60 µL), then transferring defined amounts from these intermediates to assay-ready plates. This two-step process ensures accurate final concentrations across a wide range of doses, supporting complex dose-response curves.
Optimized System Capacity
The Echo FlexCart's PicoServe storage system features four stackers with 12 positions each, accommodating plates up to 30.64mm in height. This 48-position capacity supports complete screening batches:
- Single batch with replicates: 4 tube racks, 4 intermediate plates, 12 ARPs
- Two batches without replicates: 8 tube racks, 8 intermediate plates, 24 ARPs
Integrated Automation for Complete Workflows
Beyond the Echo 655 acoustic dispenser, the system integrates numerous automated components:
- ACell Robot: Handles plate movement throughout the workflow and features Robotic Vision, which allows you to AutoTeach your robot in minutes, not hours.
- PlateLoc, Plate Peeler (formerly XPeel), and Certus Flex: Manage plate sealing and desealing operations
- MicroSpin: Ensures proper sample mixing when needed
- LVL Acoustic Decapper: Automated tube decapping on an adjacent table
- Agilent Labeller (VCode): Tracks samples throughout processing
- PlateOrient and Barcode Scanner: Ensure proper plate positioning and identification
This comprehensive integration minimizes manual intervention while maintaining full traceability throughout the screening process.
Echo Integration Modes
The system offers multiple integration modes with CellarioScheduler software to match your laboratory's sophistication:
- Echo Liquid Handling Software Only: Simple, repetitive patterns defined in Echo's base software
- Map Files: More complex repetitive patterns defined in CSV format; you can vary map files using scripting or parameters
- Cherry Picking: Complete batch transfers defined in a single CSV list with plate barcodes (using the CP/IC50 operation).
Most dose-response workflows use the Cherry Picking mode (Mode 3), which provides the flexibility needed for both fixed and variable protocols.
Future-Ready Design
The system's modular design enables expansion as laboratory needs evolve. Available deck space accommodates future integration of an incubator and plate reader, allowing the platform to execute complete assays rather than just preparing plates. This upgrade path lets laboratories begin with plate preparation and seamlessly scale to full screening workflows without system replacement. For instance, adding these modules would enable direct execution of mix-and-read assays such as CellTiter-Glo, transforming the system from a prep station into a complete screening solution (Fig. 9).
Figure 9. Expansion opportunity to add incubator and plate reader to the system to automate compound screening, allowing them to also perform mix-and-read assays such as CellTiter-Glo.
Operational Flexibility
The Echo FlexCart operates through HighRes Biosolutions' CellarioScheduler software, which can be controlled via remote desktop when properly configured behind a company firewall. While manual startup is currently required, this remote access capability enables researchers to initiate runs outside normal working hours, maximizing system utilization.
The Bottom Line
The Echo FlexCart system represents a thoughtful balance of automation, flexibility, and throughput for compound screening laboratories. Whether your lab runs identical dose-response curves daily (Option 1 - Fixed) or requires the flexibility to adapt protocols for different screening campaigns (Option 2 - Variable), the system's dual-protocol approach ensures you're never locked into a one-size-fits-all solution.
By combining acoustic dispensing precision with intelligent workflow design and comprehensive automation, the Echo FlexCart helps laboratories achieve faster turnaround times while maintaining the accuracy essential for drug discovery. It's not just about speed—it's about delivering reliable, reproducible results that advance your research from compound to candidate more efficiently than ever before.
Interested in learning how the Echo FlexCart system can enhance your compound screening workflows? Tell us about your project and explore customization options for your laboratory.