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Overview

Open a whole new world of bioprocess development when you use LIS to perform automatic feeding in shake flasks. Simply assemble the components, define the experiment parameters, fill the cartridge with the feeding liquid, and start feeding.

Key Features

  • Automated feeding of liquids into shake flask cultures
  • Flexible feeding rates
  • Control and monitor your feeding experiments wirelessly with the DOTS Software

Benefits

  • Introduce bioreactor-like feeding and control options into your shake flask experiments
  • Avoid process interruptions, like stopping your shaker of moving the flask
  • Align feeding and control strategies of your shake flask screening experiments with later bioreactor runs

Current Shake Flask Challenges

Lack of Control
  • Lacks bioreactor control options for e.g., pH control or fed-batch
  • Leads to inconsistencies in scale-up between shake flask and bioreactors
Disadvantageous Manual Feeding
  • Requires hours of manual, hands-on time
  • Causes process interruptions, risk of contamination, and loss of culture volume
  • Limits complex feeding strategies

How It Works

Automation enables standard use of complex feeding schedules.

Liquid Injection System (LIS)

In order to dispense a defined amount of liquid from the cartridge, the drive pumps air through a sterile filter into the cartridge according to the feeding profile. 

Liquid Injection System (LIS)

After the dispense step, the drive rebuilds negative pressure to keep the remaining liquid in the cartridge.

Application Data & Results

Explore applications in real-world situations. Looking for something specific? Contact us to see data for your organism and application.

Enable Fed-batch Cultivations

With LIS, typical bioreactor processes, like fed-batch cultivations, can be recreated in shake flasks. Fed-batch cultures support the growth of S. cerevisiae on potato waste because the concentration of growth inhibitors in the medium can be controlled. With the LIS, these process conditions could be imitated on a shake flask level. 

Read the Success Story →

Batch vs fed-batch growth of Saccharomyces cerevisiae
Saccharomyces cerevisiae,  500 mL Shake Flasks, 50 mL Filling Volume, 25°C, 125 rpm
Promotor Induction in Pichia pastoris with Biomass-based feeding
Pichia pastoris, 250 mL Shake Flasks, 10 mL Filling Volume, 50 mm Throw, 30 °C, 300 rpm

Promotor Induction with Biomass-based feeding

Process control for improved protein production.

Enable feedback-controlled feeding in your shake flask experiments when you connect LIS with reliable biomass monitoring sensors such as the Cell Growth Quantifier (CGQ), or Multiparameter Sensor (MPS), and the DOTS Software. Biomass-based feeding can be used to initiate methanol induction at the optimal time - once cell growth on the primary substrate (glycerol) is complete and sufficient biomass was generated, indicated by a reduction in growth rate.

Read the Success Story →

DO-based Feeding with PID Controller

Bioreactor-like feedback control for Pichia pastoris cultivations in shake flasks.

With a DOTS-integrated controller, the methanol feed (carried out with the Liquid Injection System) was adjusted to start repeatedly, always when the DO level, monitored by DO Sensor Pills, reached a preset threshold. By using this feature, methanol was always fed as soon as the cells recovered from the previous shot, enabling ideal cell viability, while keeping promotor activity constant. Biomass was monitored additionally, with the Multiparameter Sensor (MPS).

DO-based feeding with 40% methanol
Pichia pastoris, 250 mL Shake Flasks, 10 mL Filling Volume, 50 mm Throw, 30 °C, 300 rpm

Want to see data for your organism or application?

We have tested over 100 microorganisms for more than 50 different applications with our technology.

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Hardware & Software Components

LIS Drive

LIS Drive

The drive is a programmable miniature pump that controls when and how much liquid is fed from the cartridge into the flask.

LIS Cartridge

LIS Cartridge

The cartridge is a  pre-sterilized, ready-to-use container that fits on top of the shake flask. It can be filled with up to 25 mL of any type of liquid and acts as a reservoir during the feeding experiment.

DOTS Software

SBI-Icon-dots-software-computer-2

The DOTS Software allows you to wirelessly control and monitor your feeding experiments. Create individual feeding profiles, define feeding parameters, and monitor the expensed liquid volume over time. By combining other DOTS integrated sensors, parameter-based feeding can be realized.

What Our Customers Are Saying

"Overall, the LIS system is easy to assemble, reduces manual work significantly, and allows us to test multiple feeding profiles, including linear and exponential feeding.”

-Prof. Dr. -Ing. Frank Eiden (Westphalian University of Applied Science)
WHS
"LIS- and CGQ-system turns nights and weekends into productive times for the preparation of optimal inocula and for the first time leverages the early stages of culture expansion to a level of bioprocess monitoring and control that has until today only been accessible in later stage stirred tank bioreactors.”

-FermFactory (RWTH Aachen University)
FermFactory (RWTH Aachen University)
"With the DOTS platform I can combine sensors and actuators in a simple way to perform completely new applications like biomass-based feeding in shake flasks. My shake flasks can now operate similar to small-scale bioreactors, keeping the ease and cost-effectiveness of flasks but adding the sensor and control options of bioreactors. This is truly revolutionary for me and my experiments."

-Christoph Kutzner (Badische Peptide & Proteine, Heidelberg)
Badische Peptide & Proteine-1
"By using the LIS, I can now continuously feed glucose in shake flasks. This improves the transferability of results from shake flask experiments to bioreactor runs."

-Dr. Kambiz Morabbi Heravi (Project Manager, Strain Engineering, Clariant)
Clariant_Logo-1

Specifications

Compatible Laboratory Infrastructure

The LIS is designed to fit any 38 mm straight neck Erlenmeyer shake flask.

LIS has been successfully tested with a broad variety of liquids. Our team of application scientists will work with you to ensure that the liquid and concentration needed for your particular application can be used with our feeding system. 

  • Sugars

  • Alcohols

  • Glycerol

  • Acids, bases, and inductors (e.g., IPTG)

  • Antifoam

 

Can I feed multiple solutions at the same time with LIS?

No. The LIS is designed to hold one liquid at a time in its single reservoir (cartridge). To switch to a different feeding solution, the cartridge must be replaced, which requires setting up a new LIS assembly (drive + cartridge) and restarting the feeding mid-run. It is not possible to feed two liquids at the same time with LIS.

Does the LIS setup close the shake flask airtight?

No. The LIS setup closes your shake flask in a similar way as an aluminium cap and allows for gas exchange. Check out this data set comparing the evaporation rates of shake flasks with different closing types. It shows that a LIS closing does not limit gas transfer in comparison to conventional shake flask closings.

Can I reuse the cartridges?

The cartridges are single-use products and we do not recommend to reuse them.

How much liquid can I feed per time (rate) and in total?

The LIS offers several different feeding profiles, such as single- or multi-shot injections, constant feeding, or exponential feeding, providing customized solutions for almost any experiment. Learn more on our Application Page. The cartridge has a maximum capacity of 25 mL. For best results, we recommend a filling volume between 8 and 20 mL. The smallest possible feeding volume is 100 µL. Hence, a single shot can range from 100 µL and the maximum feeding rate is 1 mL/ min.

My LIS is dripping. How do I change that?

If the setup is not carried out correctly, it may not be completely sealed, which can result in leaks or dripping. Therefore, it is essential to handle the setup carefully and follow every step in the procedure. For a detailed, step-by-step demonstration, please refer to our How to video under Resources (on this tabber).

Some common mistakes that can lead to leakage include:

1) Forgetting to auto-offset the pressure of the Drive. Always ensure the pressure is auto-offset to 0 before starting the experiment; otherwise, the setup is unlikely to be leak-proof. This auto-offset must be done with the Drive alone, without cartridges or filter added.

2) Omitting the sterile filter. Each cartridge comes with a sterile filter that must be attached. Do not forget to include it.

3) Removing the luer-plug too early. Always prepare the drive and wait for the LIS Drive to stop pumping before removing the luer-plug. This allows the pump to create an underpressure that keeps the liquid in place.

4) Not filling the cartridge nozzle (LIS outlet) completely. Ensure the tip is filled completely with liquid and no air bubble is present at the bottom of the cartridge before starting an experiment.

5) Using the wrong liquid parameters that specify the liquid in use. When using parameters that differ (sometimes even slightly) from the used liquid, dripping is possible.

6) Stating the wrong filling volume: Filling the Cartridge with more or less liquid than stated in the software can lead to dripping.

Which liquid types can I feed?

LIS has been successfully tested with a broad variety of liquids. These include (but are not limited to) a broad range of sugars, alcohols, acids, and bases. The liquid type needs to be specified in the Software- select the option that most closely matches your liquid. If you cannot find your liquid in your list or are unsure if it resembles the liquids from the list sufficiently, please contact our support team.

Can I feed volatile liquids, such as methanol, with the LIS?

Yes, but feeding volatile liquids introduces some challenges. Volatile liquids (e.g., highly concentrated methanol) can evaporate continuously. This causes the Drive to pump more frequently, which may reduce the negative pressure and potentially lead to dripping. There are certain countermeasures that help to prevent these. Please, reach out to our service team for advices.

Can I sample my flasks during the feeding process?

It is not recommended to remove the LIS setup during the experiment. If you plan to sample during the experiment, we recommend to use a 2-neck shake flask and use the second neck to withdraw samples. (Be careful not to tilt the flask excessively, as this may wet the filter.)

How do I clean my system? Can I autoclave it?

The LIS Drive must not be autoclaved, as this will destroy the device. It should also never come into contact with water. If the Drive got dirty, clean it carefully using a slightly wet wipe (avoiding the sensitive white outlet nozzle) and then dry it thoroughly. The cartridges and filters are single-use components. They are pre-sterilized with ethylene oxide, packaged sterile, and therefore do not require any additional cleaning or sterilization.

Vessel Types

Compatible Laboratory Infrastructure

The LIS is designed to fit any 38 mm straight neck Erlenmeyer shake flask.

Liquids

LIS has been successfully tested with a broad variety of liquids. Our team of application scientists will work with you to ensure that the liquid and concentration needed for your particular application can be used with our feeding system. 

  • Sugars

  • Alcohols

  • Glycerol

  • Acids, bases, and inductors (e.g., IPTG)

  • Antifoam

 

Resources
FAQs
Can I feed multiple solutions at the same time with LIS?

No. The LIS is designed to hold one liquid at a time in its single reservoir (cartridge). To switch to a different feeding solution, the cartridge must be replaced, which requires setting up a new LIS assembly (drive + cartridge) and restarting the feeding mid-run. It is not possible to feed two liquids at the same time with LIS.

Does the LIS setup close the shake flask airtight?

No. The LIS setup closes your shake flask in a similar way as an aluminium cap and allows for gas exchange. Check out this data set comparing the evaporation rates of shake flasks with different closing types. It shows that a LIS closing does not limit gas transfer in comparison to conventional shake flask closings.

Can I reuse the cartridges?

The cartridges are single-use products and we do not recommend to reuse them.

How much liquid can I feed per time (rate) and in total?

The LIS offers several different feeding profiles, such as single- or multi-shot injections, constant feeding, or exponential feeding, providing customized solutions for almost any experiment. Learn more on our Application Page. The cartridge has a maximum capacity of 25 mL. For best results, we recommend a filling volume between 8 and 20 mL. The smallest possible feeding volume is 100 µL. Hence, a single shot can range from 100 µL and the maximum feeding rate is 1 mL/ min.

My LIS is dripping. How do I change that?

If the setup is not carried out correctly, it may not be completely sealed, which can result in leaks or dripping. Therefore, it is essential to handle the setup carefully and follow every step in the procedure. For a detailed, step-by-step demonstration, please refer to our How to video under Resources (on this tabber).

Some common mistakes that can lead to leakage include:

1) Forgetting to auto-offset the pressure of the Drive. Always ensure the pressure is auto-offset to 0 before starting the experiment; otherwise, the setup is unlikely to be leak-proof. This auto-offset must be done with the Drive alone, without cartridges or filter added.

2) Omitting the sterile filter. Each cartridge comes with a sterile filter that must be attached. Do not forget to include it.

3) Removing the luer-plug too early. Always prepare the drive and wait for the LIS Drive to stop pumping before removing the luer-plug. This allows the pump to create an underpressure that keeps the liquid in place.

4) Not filling the cartridge nozzle (LIS outlet) completely. Ensure the tip is filled completely with liquid and no air bubble is present at the bottom of the cartridge before starting an experiment.

5) Using the wrong liquid parameters that specify the liquid in use. When using parameters that differ (sometimes even slightly) from the used liquid, dripping is possible.

6) Stating the wrong filling volume: Filling the Cartridge with more or less liquid than stated in the software can lead to dripping.

Which liquid types can I feed?

LIS has been successfully tested with a broad variety of liquids. These include (but are not limited to) a broad range of sugars, alcohols, acids, and bases. The liquid type needs to be specified in the Software- select the option that most closely matches your liquid. If you cannot find your liquid in your list or are unsure if it resembles the liquids from the list sufficiently, please contact our support team.

Can I feed volatile liquids, such as methanol, with the LIS?

Yes, but feeding volatile liquids introduces some challenges. Volatile liquids (e.g., highly concentrated methanol) can evaporate continuously. This causes the Drive to pump more frequently, which may reduce the negative pressure and potentially lead to dripping. There are certain countermeasures that help to prevent these. Please, reach out to our service team for advices.

Can I sample my flasks during the feeding process?

It is not recommended to remove the LIS setup during the experiment. If you plan to sample during the experiment, we recommend to use a 2-neck shake flask and use the second neck to withdraw samples. (Be careful not to tilt the flask excessively, as this may wet the filter.)

How do I clean my system? Can I autoclave it?

The LIS Drive must not be autoclaved, as this will destroy the device. It should also never come into contact with water. If the Drive got dirty, clean it carefully using a slightly wet wipe (avoiding the sensitive white outlet nozzle) and then dry it thoroughly. The cartridges and filters are single-use components. They are pre-sterilized with ethylene oxide, packaged sterile, and therefore do not require any additional cleaning or sterilization.

Customer Success Stories

SBI-Success-Table-6

How to optimize bioreactor inoculum in shake flasks?

This application note illustrates the use of LIS in conjunction with the yeast S. cerevisiae to optimize bioreactor inoculum in shake flasks. After a period of preconditioning, the LIS automatically injects different seed biomass concentrations into a shake flask containing fresh YEPD. Cell growth is monitored in real-time to assess the reproducibility of environmental and growth phase conditions.

SBI-Success-Table-8-1

LIS WIDENS THE APPLICATION AREA FOR SHAKE FLASKS, E.G., TO DETERMINE THE BEST  PRODUCTION STRAIN.

The batch condition has a great impact on the cell's metabolism which overshadows the strain's characteristic protein production behavior. A LIS facilitated fed-batch process showed a significant increase (30%) in active protein yields, compared to a batch process and is better suited to screen for the best production strain. 

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