DISCOVER 
MOLECULAR
INTERACTIONS

Kinetics – Affinity – Avidity
Conformational Changes
Thermodynamics

heliX®

Scientific discovery is
not a straight line.

Versatility is key

Take advantage of heliX® versatile,
robust and scalable design. 

heliX®

Product portfolio overview.

Measurement
modes.

The switchSENSE® 
principle.

The principal functional elements of switchSENSE® are DNA nanolevers,
which can be electrically actuated to oscillate at high frequencies.

The high frequency dynamic electrical switching mode probes the hydrodynamic friction of analyte molecules and serves to determine the size and shape of biomolecules. When analytes bind to oscillating DNA nanolevers on the sensor spots, the nanolever movement is slowed by the additional friction imposed by the analyte, thereby revealing its size or shape changes.

 

The fluorescence proximity sensing mode detects the binding of molecules in real-time through changes in the dye`s local environment.

The unique use of two different fluorophores makes it possible to monitor two independent signals from two interactions at the same time and on the same sensor spot. It also enables fluorescence resonance energy transfer (FRET) experiments, for binding and conformation analyses that require the resolution of intra-molecular distance changes with sub-nm resolution.

 

Nanolever switching
dynamics
measurements.

Measurement of the electrically actuated DNA nanolever motion. Left: Low alternating voltages repel (attract) the nanolever from (to) the sensor. The fluorescence brightness indicates the nanolever orientation, because energy transfer gradually quenches the fluorescence emission when the dye approaches the gold sensor. Right: Time-resolved nanolever switching dynamics. Analyte molecules binding to the nanolever alter the friction and/or the local chemical environment of the dye, which is detected as changes in the switching speed and/or fluorescence intensity.

Protein friction measurement: 
size and conformation.

switchSENSE® is the only biosensor capable of measuring molecular dynamics on a chip, ideally suited for the analysis of protein sizes and conformations.

The measured instantaneous velocity of the nanolever depends on the hydrodynamic friction of the analyte and hence reveals protein size and conformation.

Unparalled sensitivity and accuracy for protein sizing
switchSENSE® delivers unrivaled accuracy in the size range between 1 and 25 nm, which is crucial when dealing with proteins and macromolecular complexes. Changes in hydrodynamic diameters as small as 0.1 nm can be resolved.

Low Sample Consumption
5 pmol of protein per measurement, i.e., 1/1000th the amount required for a DLS measurement.

Any environment
High or low salt, high or low viscosity, high or low pH.

“Give me a lever long enough […] and I shall move the world.”
Well put, Archimedes!
We designed the Adapter Chip to fit any kind of lever. Short and slender for small proteins, long and rigid for large proteins or protein complexes.

Turnkey conformational
change
analysis.

heliX® measures conformational changes in real-time by directly comparing the hydrodynamic friction (switching speed) of two molecules on two adjacent sensor spots.

Conformational changes are expressed as %-friction-change, which works for any protein or nucleic acid state in almost any environment. Hence, molecular conformations can be investigated early in the discovery process, without previous knowledge about a sample.

Simply define your initial state and measure change.
Anything may serve as a reference, for instance:

  • bare DNA nanolevers without attached proteins
  • the protein conformation before small molecule binding
  • a protein mutant that cannot undergo conformational changes
  • a surrogate protein
  • a particular DNA or RNA fold

Follow the line.

See heliX® in action. 

Schedule a demo today. 

heliX® modular design.

Versatile, robust, scalable.

Combine as many heliX® modules as you require to scale-up throughput to your needs. 

Spacecrafts are built from independent modules, 
because modularity means versatility and reliability.

You don’t need to wear a spacesuit when operating a heliX®,
but you can rely on the same design principles.

Combine as many heliX® units as you like in one heliOS network.

Run different assays simultaneously,
or in parallel for maximal throughput.

Throughput, 
scalable to your needs.

heliX® adapter chip.

heliX® sensor functionalization.

heliX® chip and sensor functionalization must be so routine that your mind is free to focus on your samples

Automated sensor exchange

Load up to 5 chips in one rack and switch automatically between 5 channels and 10 sensor spots.

 

RFID near field communication

between instrument and chip for seamless traceability of chip status and usage history.
Ideal for quality-controlled GxP environments and consistent, error-free results.


Download the heliX app to read-out the status and usage history of any heliX® chip with your mobile device.

 

Robust microfluidics

Simplistic single-channel design, made from durable glass, withstanding highest flow rates and corrosive chemicals, disposable.

 

2 detection spots x 2 colors

For real-time referenced measurements of 2 interactions, or monitoring of up to 4 interactions simultaneously.

Use the heliX® chip app to read 
the status of your biochips.

Scan biochips with your smartphone.

The heliX chip app allows you to read out the status and usage history of any heliX® chip with your mobile device.

Chip Scanner

Identify the chip type and ID.
Check the date of first use and the status of your chip.
Verify the expiration date.
How many hours has the chip been in use?
How many times has it been regenerated?
What temperatures had the chip been exposed to?

Specification Sheet

Download the spec sheet for more information.

Compatible Kits

Directly access a list of compatible coupling and adapter kits.

Contact Us

Contact a specialist for technical support and assay development. 

Order Chip

Conveniently place an order.

 

heliX® chip functionalization.

A robust way of tethering molecules to a surface sensor.

DNA duplexes are forming, separating, and re-forming successfully since first life forms appeared on earth. 3.7 billion years later we are using DNA helix formation to zip molecules onto sensor spots. Sorry for taking so long, but we wanted to be sure it works just fine.

heliX® chip with DNA anchors

The heliX® chip surface is modified with covalently attached single stranded DNA anchor sequences, which have been optimized to bind adapters with ultimate specificity and stability. The 48-mers are carefully selected and remain double-stranded up to 80°C.

 

Ligand (capture) strand, exchangeable

Your molecule of interest (the ligand) is immobilized onto the surface by the DNA nanolever, either by direct covalent coupling or by tag-capturing methods. Coupling of proteins or small molecules to ligand-strands is readily performed using easy-to-use coupling kits.

 

Adapter strand, exchangeable

Adapters give you maximal experimental flexibility: use a standard adapter for most binding and conformation applications, or pick a long DNA-origami nanostructure to size the largest molecular complexes. Dyes are exchangeable, too.

Molecular lego, basically.

Working with adapter strands.

Reporter fluorophore

Our standard red and green fluorophores work for almost any application, reporting slightest changes in its molecular environment with high sensitivity. But experimental creativity cannot be predicted, so pick your optimal probe from a wide range of chemically diverse dyes. Rhodamines, cyanines, oxazines, acrinidines and others are available on stock and custom synthesis is supported, too… your choice. heliOS software supports pre-configured screening workflows to identify your preference in green and red with little effort.

Easy to adapt

Kits with ready-to-use solutions and pre-configured heliOS software workflows.

Standard adapter

A single-stranded sequence with 96 bases, modified with a reporter dye in green or red. The upper 48 bases bind the ligand strand. Sequence information is openly available, in case you’d like to custom-make your ligand strands instead of using a DBS coupling kit.

 
DNA nanostructures: Think big or small. Flexible or rigid. Mono or bi-specific.

Standard heliX® chips can be combined with DNA nanostructures such as flexible, antibody-like Y-structures presenting two ligands. Or rigid 50 or 100 nm long DNA-origami nanolevers to actuate and size large molecular complexes.

Ligand strands are compatible with standard adapters as well as with DNA nanostructures. Couple ligands just once and run assays with different adapters without additional effort.

 

Sensor functionalizing through standard,
automated workflows

Sensor functionalization must be so routine that your mind is free to focus on your samples.
The switchSENSE®  workflow is simple, reliable, and effective:

Ligand immobilization
Ligand coupling is carried out in-vitro for superior purity.

Low sample consumption
5 pmol in 20 µL adapter-ligand conjugate per immobilization.

Fast
Wash off analyte/ligand within 1 second.
Immobilize fresh ligand within 1 to 5 minutes.

Fresh ligand, every time
For reproducible results, every time. DNA-mediated functionalization eliminates the need to scout for regeneration conditions.
Why not have a coffee instead?

Repeated chip regeneration
Confidence in chip quality over more than 50 cycles*.

Economics
Less than $2 per datapoint for chip and reagent costs*.

* Numbers reflect typical workflows and can vary depending on experimental conditions.

heliX® chip.

Exchangeable ligand / capture strand. 

MIX and RUN!

Ligand density control made easy on a heliX® chip.

Adjusting different ligand densities on a heliX® Adapter Chip is easier than preparing a decent Vodka Martini:

  1. Mix ligand and adapter strands at the desired ratio.
  2. Shake or stir, it doesn’t really matter. Place vial in autosampler.

Follow the line.

See heliX® in action. 

Schedule a demo today. 

heliX® Instrument and Software.

Unique design features.

modular connection to heliOS network

Autonomous device operation with embedded control system.
Stable data transfer to control PC.

 

optics

4 single photon fluorescence counters.
Cell imaging.

 

microfluidics

Advanced fluidics for rapid liquid exchange.
Separate line for in-run washing.

 

autosampler

384 and 96 well plates.
Temperature controlled sample compartment.

 

automatic
chip loader

Automatic exchange of 5 chips.
RFID tags for seamless traceability.

 

temperature control

Sample temperatures range from 10°-70°C.
Measurement in temperature gradient 10°C / min.

 

When it comes to fluidics
don´t compromise. 

Conclusive results come from quantifyable measurements.

Measure real-time kinetics without cross contamination, mass-transport limitations, or rebinding artefacts.

The heliX® fluidic system has been designed as best-in-class to enable the quantitation of fast and slow kinetics (10+1 – 10-6 s-1) with confidence.

  • Advanced fluidics design for rapid solution exchange.
  • Precision valves and flow sensors for feedback controlled flow.
  • High flow rates up to 2000 µL/min for artefact-free
    measurements of rapid kinetics.
  • 3 separate flow lines for immaculate results:
    sample line, buffer line, wash line.
  • In-run washing of sample line during dissociation phase.
  • 3 pumps per module for maximal precision and in-run wash steps.
  • Disposable chip with integrated micro-fluidic channel.
  • Low maintenance, no expensive integrated flow cartridge (IFC).
  • LC-grade durable tubing materials for the use of most effective cleaning solutions.
  • Compatible with single-use technologies for GxP environments.

heliX®optical detection system.

For sensing and molecular dynamics measurements. 

Fluorescence is the most sensitive and most versatile method to probe molecular processes.

Combine fluorescence sensing with time-resolved single-photon counting technology to get superior performance that is applicable to almost any molecular experiment.

  • Epi-fluorescence set-up with high-numerical aperture for optimal photon collection.
  • Simultaneous detection of four signals (2 x 2) by four single-photon detectors.Two-color dection, red and green, from each sensor spot.
  • Two detection spots in each flow channel for real-time referencing of two colors or multiplexing of four interactions.
  • Proprietary E-TCSPC electronics (Electrically-triggered Time Correlated Single Photon Counting) for nanolever switching speed measurements with 0.1 µs resolution.
  •  

Measurement Modes

  • Detection of molecular binding via fluorescence proximity sensing.
  • Analysis of molecular friction (conformational) changes by E-TCSPC nanolever switching speed measurements.
  • Analysis of binding and conformational changes via two-color FRET.
  • Cell imaging with CCD camera.
  • Integrated reflected light microscope with high contrast.
  • Capable of automated recording of z-stacks.

heliX® temperature control. 

Accurate temperature control is a pre-requisite to any meaningful biophysical experiment with proteins or nucleic acids.

heliX® pushes the boundaries of what has been possible with state-of-the-art biosensors by making a temperature range from 10°C to 70°C accessible for measurements of affinities, kinetics, and conformational changes at constant temperatures or in temperature gradients.

This is feasible because switchSENSE®, unlike other biosensors, utilizes a robust fluorescence measurement rather than a refractive index readout, which is  notoriously temperature-sensitive.

Biochips

Sensor chip temperatures are adjusted by high-power feedback controlled thermoelectric elements between 10°C and 70°C. Measurements in temperature gradients can be performed at ramp speeds of up to ±10°C/min.

Only the measurement chip is subjected to the adjusted temperature, while other chips in the rack are kept at room temperature for optimal long-term stability.

Autosampler

Samples are kept at constant temperatures in a thermally isolated, closed compartment.

Normally operated as a refrigerator to extend sample lifetime, any temperature from 4°C to 40°C may be adjusted according to experimental requirements.

heliOS software.

Intuitive and powerful.

A powerful software package to plan, perform and analyze your switchSENSE® experiments.

ASSAYS & WORKFLOWS

Choose from a variety of optimized workflows to quickly design your optimal assay, or define new workflows from scratch and add them to your library for customized applications.

Quick-start assays with a few clicks using intuitive experiment planning modules. Get suggestions for best-practice parameter values. Build fully customized assays from workflows simply by drag-and-drop.

DATA ANALYSIS

Powerful data analysis modules are designed for versatility and efficient batch processing of large datasets. Extract kinetic rate constants, affinity, avidity, conformation, and thermodynamic information with confidence. Take advantage of a number of graph templates to render data display comprehensible and meaningful. Export graphs and data for further processing, or save time using pre-defined quick reports.

DEVICES

Manage the utilization of heliX® modules in your network and send assays to available modules.
Each heliX® unit features an embedded PC to run measurements autonomously, for uninterrupterd operation.

Rate-scale plot to illustrate the individual and conjoint actions of two arms of a bispecific antibody.

Real-time sensorgram of a 9 base-pair DNA interaction.
Grey lines are baseline-subtracted, unreferenced experimental data.
Binding rate constants are analyzed  from single exponential fits (pink and blue lines), without the need to apply MTL models.

Conformational change analysis of a small molecule screen. Blue are inducers of extended protein conformations, pink are inducers of protein compaction. Right: histogram of binned data for cluster identification.

Follow the line.

See heliX® in action. 

Schedule a demo today. 

Applications.

switchSENSE® in the drug discovery process.

The high information content provided by switchSENSE® lowers attrition rates of drug candidates in late, expensive stages of drug development. 

switchSENSE®

for nucleic acid binding molecules

DNA/RNA Binder Kinetics

Association and dissociation rates.
Real-time target specificity control.
Aptamer folding induced by small molecules.

DNA/RNA binding molecules:

  • DNA damage repair
  • Transcription factors
  • Translation initiation
  • Splicing factors
  • Charged peptides

Enzymatic Activity

Separate binding from catalytic activity.
Incorporation rate of modified nucleotides.
Dose Response of small molecules.

DNA/RNA modifying enzymes:

  • Polymerases
  • Reverse Transcriptases
  • Helicases
  • Nucleases
  • Ligases, etc. 

switchSENSE® FEATURES

  • Rapid DNA/RNA target exchange
  • Temperature control 8 – 70°C
  • Low sample consumption

  • Native binding setup (protein in solution)

switchSENSE®

for the analysis of multi-specific antibodies

switchSENSE® FEATURES

  • Straightforward sensor functionalization with two different antigens.

  • Variable ligand density to control interlinking when multivalent binders are measured.

  • Easily adjustable antigen surface ratios to mimic cell surface abundances.

  • Two-color detection to monitor each interaction individually.

  • Stable signals for long dissociations to measure slow avidity off-rates.

  • heliOS software with multi-phasic fitting algorithms to differentiate affinity from avidity.

switchSENSE®

for the analysis of protein diameters 
and 
conformational changes

switchSENSE® FEATURES

  • Low sample consumption of only 5 pmol protein per measurement (i.e., 1/1000th of a DLS measurement).

  • Straightforward interpretation of results: compaction or extension in % friction change.

  • Unrivaled accuracy in the size range important for protein (complexes), i.e. 1 – 25 nm.

  • Fully automated throughput using 384/96 well plates.

  • Works in almost any environment.

Follow the line.

See heliX® in action. 

Schedule a demo today. 

heliX®

System comparison.

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