The ActiPix™ TDA200 HT Nano-Sizing System

 

INTRODUCTION

The ActiPix™ TDA200 is a benchtop high throughput nano-sizing system which enables the rapid determination of size and purity for a range of molecules including proteins, antibodies, nanoparticles and quantum dots. It measures the hydrodynamic radius and diffusion coefficient for species in solution.

Key features and benefits include:

· Low sample requirement - between 10 to 100 nL of sample are injected into the system for each measurement. Low volume sample vials ensure no wastage of precious sample.

· Measures hydrodynamic radius for concentration range from 0.1 to 100 mg/mL. No dilution or sample preparation required.

· Fast - Most runs completed in less than five minutes, enabling faster decision making and less system downtime.

· Sample held in a temperature controlled environment from 4-40 oC during analysis. This ensures samples are held at optimum conditions for a variety of studies.

· Automated run lists allow multiple samples to be run overnight.

· Ideal for membrane proteins where surfactants are used. The TDA200 uses UV absorbance of the species to determine hydrodynamic radius. As detergents are typically invisible to UV light, difficult samples such as membrane proteins are easy to characterise without interference from surfactant micelles.

Overview of the ActiPix™ TDA200 Nano-Sizing System

DESCRIPTION OF TECHNIQUE

The TDA200 Nano-Sizing System uses a novel approach to measure the hydrodynamic radius for proteins, antibodies and nanoparticles. It utilises Paraytec’s award winning UV area imaging technology to capture high resolution absorbance data of the sample as it moves through a capillary . The technique allows analyses to be performed with up to 10 buffer samples in a sequence, enabling size measurements to be made for the samples in their native, aggregated or denatured forms.

Using a high precision injection system, a 10 to 100 nL slug of sample is introduced into the flowing stream contained in a looped capillary represented in Figure 1.  The capillary, internal diameter typically 75 µm,  has 2 detection windows along its length which enable absorbance measurements of the sample to be recorded at two different times using the ActiPix™ area imaging detector. 

Figure 1. Illustration of an open ActiPix™ Nano-Sizing cartridge. The capillary loop can clearly be seen to the right of the picture.  The two detection windows are labelled.

Figure 1. Illustration of an open ActiPix™ Nano-Sizing cartridge. The capillary loop can clearly be seen to the right of the picture. The two detection windows are labelled.

Whilst peak areas are the same, since area is proportional to the amount of sample injected, the widths of both peaks are different due to Taylor dispersion. The signal from the second window has a greater width and lower amplitude than the first window as shown in Figure 2.  The data are automatically processed using Equation 1 below to provide absolute values of diffusion coefficient and hydrodynamic radius.

Figure 2. Illustration of the change in peak profile as due to Taylor Dispersion as a slug of sample is pushed through a capillary.

Figure 2. Illustration of the change in peak profile as due to Taylor Dispersion as a slug of sample is pushed through a capillary.

Taylor dispersion analysis (TDA) provides an absolute, simple and rapid method for determining diffusion coefficients and hydrodynamic radii.

In the TDA200 Nano-Sizing System, UV area imaging with two measurement points allow all data to be collected extremely quickly in a single experiment. The peaks are automatically fitted with a fitting function using Paraytec’s ActiPix™ TDA200 HT Nano-Sizing Software.

The area under the peak corresponds to the amount of sample injected. The times and variances of the two peaks are used to calculate the hydrodynamic radius of the sample.  The ActiPix™ Nano-Sizing software presents the data in a convenient format.

This technique can also be used determining the radii of multiple components of different sizes in the same sample, as shown in Figure 3. Paraytec’s fitting functions deconvolute multiple  Gaussian peak functions until the best quality of fit data is reported.

Example results from the TDA200

Example results from the TDA200

Table 1 shows typical results obtained from the TDA 200 Nano-Sizing System.  The system can be used to precisely size a range of species with hydrodynamic radii from 0.3 nm to >20 nm.

*   Multi-Component Fit, # Approximate diameter determined by  TEM

SAMPLE REPORT

Powerful ActiPix™ software automatically generates detailed reports for each sample analysed. An example of a  report is shown below. The software also enables the user to manually process data if required.

SYSTEM REPEATABILITY

The TDA200 Nano-Sizing System ensures data quality remains consistent from one day to the next.

SPECIFICATION

Controller

Light source                                                                  Pulsed xenon lamp, nominal rate 20 Hz

Wavelengths                                                                190 - 1100 nm, filter selectable

Filter bandpass                                                            10 nm

Measurement range: caffeine                                      1 ppm (5 µM) to 5000 ppm (26 mM) at 254 nm

Measurement range: protein                                        0.1 mg/ml to 150 mg/ml at 214 nm

Baseline noise                                                              10 µAU RMS

 

Imager properties

Spatial resolution                                                          7 µm x 70 µm

Pixel size                                                                      7 x 7 µm

Imager area                                                                  9 x 7 mm (W x H)

Remote sensor head size                                            6 x 6.5 x 11 cm (H x W x L)

 

Sizing cartridge

Detection pathlength                                                    75 µm

Capillary length                                                            150 cm

 

Autosampler and pressure drive

Linear flow rate                                                             1 mm/s to 20 mm/s selectable

Injection volume                                                           10 - 100 nL selectable

Temperature Range                                                     4 - 40 oC

Vials                                                                              300 µL or 4 mL glass

                                                                                      Adaptors for 250µl centrifuge tubes available

 

PC

                                                                                      High specification desktop PC with 22" monitor

                                                                                      Software for multi-component sizing analysis

 

Power

                                                                                      110 – 240 V AC 50/60 Hz

                                                                                      (4) power receptacles required as below:

                                                                                      (1) controller, (1) autosampler, (1) monitor, (1) PC

 
Bench space required

                                                                                      1 m x 1 m (Autosampler)

                                                                                      1 m x 1 m (PC)

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