Automation and high-throughput for LNP formulation screening

ALiS

The Automated Library Synthesis System (ALiS) is a NEW game-changing automated platform for high-throughput screening of LNP formulations encapsulating genetic material, such as mRNA, for early stage development of genetic medicines and vaccines.

ALiS will significantly accelerate early stage Research and Development/Discovery projects by performing up to 96 unique experiments in under 6 hours. The system works with low reagent volumes, features automatic wash cycles, Anti-dispersion Technology and interchangeable microfluidic chips. It will reduce your hands-on time and your reagent and input costs, and with a 96 well plate format, will ensure upstream and downstream workflow compatibility.

 

Unique benefits

High-throughput

Aspirate from and dispense into covered 96 well plates.

Automation

Walk away during experiments, increasing lab efficiency.

Covered 96 well plates

Reduce evaporation and cross-contamination.

Anti-dispersion Technology

Work with smaller reagent volumes.

Speed

Process up to 96 samples in 6 hours.

Flexibility

Modify both process parameters and formulations between experiments.

Cost saving

Reduced reagent use and reusable microfluidic chips.

Scalability

Scale seamlessly to protocol and process optimization.

Precision and encapsulation efficiency

Accurate control, excellent PDI 90%.

Set up your experiments and walk away

One of ALiS’ key benefits is that you can set up your experiments and walk away.

We designed ALiS to help you: to save you time, money and resource in the lab.  The key to this starts with automation.  ALiS aspirates samples from well plates containing pre-prepared mRNA and lipid formulations, collecting up to 96 nanoparticle samples in a single run, with no human intervention – all in less than a day.  The user can define and validate the experimental parameters at their desk and set ALiS running at the click of a button, leaving researchers free to get on with protocol optimization on our ANP System, using the same process technology. 

This set of experiments, show the changing of input ratios from 4:1 –> 1:4, ran in 5:54 hours, (with no manual intervention during the run)!

Benefits of ALiS

Specification and components

Quad Pump

ALiS uses Quad Pumps to aspirate reagents from well plates, drive fluids through the system flow-path, and dispense collected nanoparticle samples. Each of the three Fluid Handlers requires a Quad Pump in order to function.

Operating Pressure: 0 to 10 bar
Pressure Resolution: 0.1 bar
Flow Rate Range: 50μl to 10ml/min
Fluidic Tubing Output Connections
Input: 3.2mm OD x 1.5 mm ID
Output: 1.6mm OD x 0.8mm ID

Fluid Handler

The Fluid Handler enables the Quad Pump to aspirate/dispense fluid from/to a range of locations, including the individual wells of a 96 well plate, the wash try and wash pot for needle washing, and positioning for needle height setting. In addition, the Fluid Handler houses the distribution valves and sample loop that allow reagents/nanoparticle samples to be stored and transferred during an experiment.

Plate Format: 96 well plate

Max Well Plate Height: 43 mm

Sample Loop Volume: : 2.5 ml

Fluid Store

The Fluid Store houses the driving fluids required to move reagents and samples through the ALiS System flowpath, as well as the waste fluids generated by the system. On the front of the Fluid Store is the chip mounting rail, used to conveniently position the chip between the input Fluid Handlers and the collection Fluid Hander whilst ensuring the minimum necessary flowpath.

Input Fluid Storage: 4x 1000 ml

Waste Storage: 5000 ml

Watch our ALiS Timelapse

(running 96 experiments in 6 hours, unattended)

Let the data speak for itself

High-throughput and consistency

Reproducibility that inspires confidence.

System recovery of ALiS was tested by the addition of six spike sample formulations with no PEGylated lipid. There was a null effect on the reproducibility of subsequent samples demonstrating the efficacy of the automated wash between experiments. 

96 DOTAP LNPs produced on ALiS (FRR = 3:1:0 / TFR = 5ml/min)  

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Efficiency and efficacy

Let the numbers do the talking.

(a) Ten repeats show unprecedented control over the nanoparticle self-assembly process with measured sizes of 121 ± 5 nm and a PDI of 0.05.

(b) Looking at the encapsulation efficiency, the mRNA-LNPs consistently show ~ 90% mRNA encapsulation at N/P ratio of 6.

mRNA stability studies

Integrity of mRNA not compromised.

No negative impact on Size, PDI or Encapsulation Efficiency is observed for mRNA-LNPs stored in well plates at Room Temperature or +4 °C for 6 hours.

See our platforms in action

Would you like to see how our technology can help you with your drug development pipeline?

We would love to show you in person. Simply click on the button below to arrange a demonstration with one of our scientists and we will be in touch very soon!

Essential Documents

ALiS

Flyer

ALiS

Datasheet

Accelerate your screening

Recorded Webinar

Particle Works

Company brand brochure

Develop and produce LNPs

Scientific Poster

LNPs for Gene Delivery

Recorded Webinar

FAQ

How quickly can ALiS run 96 experiments?

This will depend on what your experiment flow rates and experiment volumes are – but as an example, running a set of 96 experiments at a total flow rate of 15 ml/min will complete in around 6-8 hours. These can of course be run in smaller blocks with a changover of well plates between experiment sets.

Is there a risk of cross-contamination between wells?

The needle of each fluid handler is washed both internally and externally after aspirating/dispensing from/to the well plates. All system tubing is also washed between experiment rows.

What is the minimum volume of input reagent that the system can handle?

The recommended minimum volume is 100 uL per input. The minimum total experiment volume would therefore be 200 uL (or 300 uL if dilution is used).

How many times can I use each microfluidic chip?

Our glass microfluidic chips are chemically robust, and can be cleaned with acids/bases/detergents to remove internal contamination. With good care and cleaning procedures, the chips can be used indefinitely. Due to the flow restrictions within the channel, a likely cause of failure may be a channel blockage that cannot be removed.

What types of particles can I make with ALiS?

ALiS is ideal for the synthesis of nanoparticles which can be produced by an experiment that mixes 2 fluids at room temperature. Prominent examples of particles that can be made using this process include Liposomes, lipid nanoparticles, polymer nanoparticles (such as PLGA or PCL). There are a number of other material types with published literature using this type of process – if you are unsure whether your particles can be made with ALiS, our team can offer you advice on this, so please get in touch!

Do I have to run all 96 experiments in a row?

No, you can choose to run as many or as few experiments as you would like. Depending on the stability of reagents, some users will prefer to run a smaller number of experiements before taking the collected product for downstream processing.

Can I use ALiS for process optimisation and pre-clinical manufacturing?

ALiS is intended for high throughput screening of a large number of sample formulations. Process parameters can also be screened using ALiS, as well as exploring a range of chip geometries (though the chip has to be changed in between experiment sets). ALiS does not have a continuous mode of operation, and therefore is not suitable for the generation of larger samples or production runs – the maximum collection volume is limited to 2 ml, where the ANP System can produce larger test samples up to 8 ml, as well as run in continuous production mode.

What is the maximum flow rate for ALiS?

ALiS uses 3 of its pumping channels for fluid handling, and 3 of its pump channels for running experiments. Each channel can pump at up to 10 ml/min, so the maximum flow rate is 30 ml/min, including dilution. At such high flow rates, larger input volumes are advised to ensure high quality samples can still be collected.

How does the automated experiment protocol work?

A table of experimental conditions (where each row is a single experiment) can be imported into the system control software (FCC 7). Each experiment row will refer to a specific well plate position on each of the 2 input Fluid Handlers. When the system runs, it will aspirate the required volume of sample from each of these wells, and load the fluid into sample loops. When the system is ready to run an experiment, these loaded fluid samples are released into the system flow path with precise timing, so that they converge on the microfluidic chip. The collection of the particles produced is managed by the collection fluid handler, which traps the particles in a 3rd sample loop, and then dispenses the particles into a designated well on the collection well plate. The system then washes, and the process repeats for each line in the imported experiment table.

What if my collected particles aren’t stable for the time it takes to complete 96 experiments?

ALiS has an in-line dilution capability to reduce the proportion of Ethanol ALiS can be paused during an experiment set to allow the collection well plate to be removed for the downstream processing of a number of samples. Replace the wellplate with an empty one, and click resume for the remaining experiments to continue.

How can I protect my well plates from environmental contamination / evaporation?

ALiS is compatible with a number of well plate covers, including heat sealed foil covers and pre-scored plate covers, which prevent ingress of environmental contaminants as well as reducing the evaporation of solvents from well plates. ALiS is not compatible with septum seals/airtight plate seals, or self-adhesive plate seals.