Transforming Tangential Flow Filtration with Microfluidic Precision

Ultrafiltration is essential in processing biomolecules for sample concentration and buffer exchange. Dead-end filtration (DEF), the traditional ultrafiltration method at lab-scale, suffers from membrane clogging, low filtration efficiency, and high sample loss.

 

Tangential Flow Filtration (TFF) overcomes these limitations by continuously sweeping fluid across the membrane surface, preventing buildup and enabling higher yields with greater reproducibility and efficiency. However, conventional TFF systems have drawbacks such as large footprints, high hold-up volumes, and labor-intensive operation, making them inefficient for lab-scale workflows.

 

The µPulse® - TFF system addresses the above limitations with a miniaturized design by combining TFF with microfluidic pumping technology. At its core is the filter chip, which integrates the membrane, diaphragm pump, and regulatory valves into a compact design. This innovation has drastically reduced the fluid path, minimizing the hold-up volume to just 0.65 mL - making the µPulse well suited for lab-scale applications.

Pulse RC Chip.1078
uPULSE v3 Final

TFF Miniaturization on a Chip

The filter chip consists of 4 plastic layers bonded together. Among the layers are air actuation channels, liquid channels, a diaphragm pump, a cluster of valves (e.g. diaphragm valve and return valve), and the membrane. The diaphragm pump switches between vacuum and air pressure to circulate the feed over the membrane.  The chip connects to the sample tube via transfer tubing, and the air supply is supplied with a silicone gasket.

upulse chip (1)

Precise Transmembrane Pressure (TMP) Control

Electronically regulated valves create a customizable TMP gradient across the membrane, optimizing filtration performance without compromising sample integrity or risking membrane fouling.

 

The customizable parameters allow users to optimize sample processing, similar to an industrial TFF system. To streamline method development, this predictive tool helps fine-tune workflows for maximum efficiency, reproducibility, and sample recovery, ensuring optimal performance across various applications.

Valves and Diaphragm

Faster, Cleaner, and More Versatile Sample Processing

With the µPulse chips, the concentration process is continuous and gradual, allowing samples to be concentrated up to 4x faster than using DEF. The chip utilizes a filtration membrane that is 50 - 75% larger than traditional DEF systems. The larger membrane, tangential velocity, and turbulence across the membrane ensure higher flux rates.

 

The filter chips are designed for both single-use and reusable applications. For workflows where purity and consistency are critical, they can be used as disposables to prevent cross-contamination. For less sensitive applications, an automated cleaning-in-place (CIP) process allows for effective cleaning and reuse with gradual performance decline.

Versatile Membrane Compatibility & Wide MWCO Range

The filter chips are designed to handle a broad range of buffers and solvents, making them suitable for diverse applications. The modified polyethersulfone (mPES) and regenerated cellulose (RC) membranes offer excellent resistance to harsh chemicals while ensuring high recovery rates. Additionally, the filter chips support a variety of molecular weight cutoffs (MWCOs). mPES and RC membranes are offered in pore sizes from 5 to 300 kDa, ensuring flexibility across various experimental needs.

Feature RC mPES
Pore StructureSymmetricAsymmetric
Temperature ToleranceLow to ModerateHigh
pH ResistanceModerate Tolerance to Extreme pHsHigh Tolerance to Extreme pHs
Chemical CompatibilityHighModerate
ChargeUnchargedThe Sulfone Group is Negatively Charged at pH 7.0
HydrophilicityHighModerate
Thermal StabilityLower Compared to PESHigh Thermal Resistance
FoulingVery LowLow
Protein BindingVery LowLow
ExtractablesVery LowLow
Flux RateModerateHigh
SuitabilityPreferred for Charged Proteins, Nucleic Acids, and LNPsPreferred for Uncharged Biomolecules

Versatile for a Broad Range of Scientific Workflows

Efficiently process lipid nanoparticles, liposomes, and polymeric nanoparticles for drug delivery and therapeutic efficacy

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Optimize the protein preparative workflow, enabling fast and gentle processes, including concentration, formulation, desalting, and refolding

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Ensure gentle and efficient removal of small unconjugated molecules from a variety of crude biomolecular labeling reactions

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Simplify in vitro synthesis of RNA, and linear or plasmid DNA, by efficient concentration and buffer exchange using our user-friendly system

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Streamline the fast harvesting of cells, extracellular vesicles, enzymes, and Virus-Like Particles (VLPs) while ensuring high product yields and quality

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Gently concentrate and exchange buffers for Adeno-associated Virus Vectors (AAVs), bacteriophages, and lentiviruses, preserving their structure for effective applications

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Optimize the formulation of DNA, RNA, and polysaccharide vaccines for optimal, stable, and cost-efficient results

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FAQs

System Selection & Comparison

What is the best small-scale tangential flow filtration (TFF) system for protein purification and concentration?

Both the µPulse and the aµtoPulse TFF systems are excellent small-scale solutions for protein purification and concentration workflows. The µPulse offers gentle, walk-away operation with a hold-up volume of 0.65 mL, making it ideal for single-sample processing. The aµtoPulse increases throughput with high-throughput automation—processing up to 54 samples per run and 4 samples in parallel—while delivering an industry-leading hold-up volume of ~0.25 mL (250 µL). Both systems provide efficient, reproducible protein concentration and buffer exchange with minimal sample loss.

 

What’s the difference between centrifugal filters and automated small-scale TFF systems?

Centrifugal filters rely on dead-end filtration, where the sample is forced directly through the membrane, often leading to clogging, uneven concentration, and material loss. In contrast, automated small-scale TFF systems like the µPulse and the aµtoPulse use tangential flow to continuously recirculate the sample across the membrane surface, preventing fouling and enabling faster, more uniform concentration. They also automate pressure control and endpoint detection, offering higher recovery, reproducibility, and true walk-away operation compared to manual centrifugation.

Sample Volumes, Hold-Up, and Recovery
Performance, Shear, and Fouling
Membranes, Compatibility & Reuse
Applications