Viscosizer TD is unique in using Taylor Dispersion Analysis with UV area imaging in microcapillary flow to enable ultra-low volume biophysical characterization of target biomolecules in solution.

Taylor Dispersion Analysis is an inherently simple experimental method, whereby a nanoliter volume sample pulse is injected into a laminar flow of matched buffer. Analysis of the time-evolved concentration profile (or Taylorgram) from UV absorption allows the molecular diffusion coefficient and hence hydrodynamic radius of solute molecules to be determined.

Viscosizer TD uses fully automated methodology to analyze stability of small molecules, peptides and proteins, and samples with mixtures of these species, even in the presence of excipients and surfactants that can be the source of measurement interference in other techniques.

Microcapillary flow methodology also allows complementary relative viscosity measurement on the same sample using Poiseuille’s law.

  • Viscosizer TD is an easy to use system with sample storage and presentation in a temperature-controlled autosampler to ensure sample integrity
  • Flexible and intuitive software interface provides fully automated test schedules and data analyses for walk-away operation
  • 40 nanoliter sample volume for molecular sizing and 6 microliter sample volume for relative viscosity
  • Total sample volume of 35 microliters required for triplicate measurements for both size and relative viscosity on one sample (15 microliter excess is recoverable)
  • UV detection for molecular sizing allows measurements at low concentration down to microgram quantities
  • Relative viscosity measurements with unique dual pass timing provides high resolution measurements with high reproducibility at low concentration and low viscosity
  • Taylor Dispersion Analysis spans an unmatched molecular size range in solution, from small molecule size, peptide size and protein size, and samples with mixtures of these species
  • Orthogonal technique for protein stability assay and protein solubility studies from candidate validation into early stage formulation development
  • Novel technique for biopharmaceutical researchers to assess peptide stability and peptide solubility
  • UV wavelength can be changed to optimize measurement sensitivity and molecular selectivity
  • Using a matched sample buffer effectively renders excipients and surfactants invisible, enabling label-free characterization of target biomolecules in complex solutions
  • Measurements are not adversely affected by the presence of a small amount of aggregates, meaning samples can be run with minimal sample preparation and without dilution or filtration

Viscosizer TD is a biophysical characterization tool that provides unique measurement capabilities for researchers assessing conformational stability, self-association and solubility of target biomolecules in complex solutions. Key application areas include:

  • Screening for developability of mAbs at early stages in the development pipeline, with ultra-low sample volume and low protein concentration
  • Optimization of lead candidates in complex buffers during formulation development
  • Assessment of Critical Quality Attributes (CQA) for biotherapeutics
  • Conducting biophysical studies of peptide-based therapeutics at low concentration
  • Advancing understanding of drug behavior at near in vivo conditions

Malvern Panalytical Viscosizer TD is an automated microcapillary flow-based system with UV area detection, to enable molecular sizing in solution and relative viscosity measurements. The instrument itself comprises three main components

  • Autosampler unit – provides temperature-controlled storage for sample vials (plus buffer, wash and waste vials), and automated sample/buffer/wash reagent delivery into the microcapillary
  • Detector head – incorporated into Autosampler unit as a separate temperature-controlled enclosure, and houses UV imaging sensor and interchangeable capillary assembly (with two detection windows)
  • Control box – houses xenon lamp and interchangeable UV wavelength filter, and electronics to handle system communications, data capture and transfer


Using the same microcapillary set up, two experimental methodologies are used to determine either the hydrodynamic size of molecules in solution, or the relative viscosity of the solution. Automated size and viscosity analyses can be run on the same sample, including replicate measurements.

Hydrodynamic size – Taylor Dispersion Analysis

  • UV wavelength filter is selected to detect sample UV-absorbing chromophores
  • Sample measurement temperature is set
  • Automatic procedures are used to clean the microcapillary and fill it with matched sample buffer
  • A sample pulse of several nanoliters is injected into the buffer
  • Sample pulse flows along the capillary under constant drive pressure, and broadens due to Taylor Dispersion
  • UV absorbance profiles of sample pulse (or Taylorgrams) are detected at two fixed windows
  • Automated data analysis of the Taylorgrams enables determination of molecular diffusion coefficient (D) and hydrodynamic radius (Rh)
  • Automatic procedures are used to clean the microcapillary ready for repeat measurements

Relative viscosity – Poiseuille’s law

  • Sample measurement temperature is set
  • Automatic procedures are used to clean the microcapillary and purge with air
  • A sample plug of several microliters is injected into the capillary under constant drive pressure
  • The sample plug edges are detected at two fixed windows along the capillary (simply by Refractive Index change) and the time between windows is measured (Δts)
  • The sample time is then referenced against the time taken for a solvent or buffer of known viscosity (e.g. water) to travel between the windows (Δtr) to enable the viscosity of the sample to be calculated
  • Automatic procedures are used to clean the microcapillary ready for repeat measurements

Parameters measured

Размер молекул (частиц):
Taylor Dispersion Analysis using UV Area Imaging
Относительная вязкость:
Poiseuille's law

General

Диапазон температур измерения образца:
4°C - 40°C(1)
Диапазон температур хранения образца:
4°C - 40°C(1)
Минимальная температура измерения и хранения:
20°C below ambient(2)
Диапазон давления:
0 - 3000mbar
Максимальное количество пробирок для образцов на цикл:
50
Примечания:

(1) Specified under NTP conditions (ambient of 20°C)
(2) Note that minimum sample measurement and storage temperature achievable is dependent upon ambient temperature

Optics

Длина волны регистрации:
200nm - 325nm
Выбираемый пользователем фильтр:
214nm; 254nm or 280nm

Parameter - size

Диапазон размеров (гидродинамический радиус):
0.2nm - 50nm
Точность::
Better than 5%(3)
Повторяемость:
Better than 2.5% RSD (within vial)
Воспроизводимость:
Better than 2.5% RSD (across vials)
Воспроизводимость:
Better than 2.5% RSD (across systems)
Объем образца:
40nl per measurement consumed (typical) plus sample residual volume of 15µl required in sample vial (recoverable)(4)
Примечания:

(3) % difference between mean result and reference result
(4) Total sample volume of 35µl required for triplicate measurements for both size and relative viscosity on one sample (with residual volume of 15µl recoverable)

Parameter - viscosity

Диапазон вязкости:
0.9cP - 50cP (or mPas)
Точность::
Better than 5.5% RSD(5)
Повторяемость:
Better than 1% RSD (within vial)
Воспроизводимость:
Better than 2.5% RSD (across vials)
Воспроизводимость:
Better than 2.5% RSD (across systems)
Объем образца:
6µl per measurement consumed plus sample residual volume of 15µl required in sample vial (recoverable)(4)
Примечания:
(5) % difference between mean result and reference viscosity

Autosampler unit (incorporates detector head)

Габариты (Ш, Г, В):
480mm x 660mm x 430mm
Вес:
43kg

Control box

Габариты (Ш, Г, В):
121mm x 315mm x 331mm
Вес:
7kg

Operating environment

Номинальное рабочее напряжение:
100/240V; 50/60 Hz
Диапазон температуры окружающей среды:
16°C - 30°C

A range of accessories are available to add versatility and application specificity to the Viscosizer TD

Viscosizer TD

Microcapillary Cartridges - Uncoated and Coated

Dual-pass microcapillary cartridges for accurate size and viscosity analysis

Image

Microcapillary cartridges comprise the capillary itself which is assembled into a plastic insert with two precision windows, to allow easy and direct mounting into the detector head. Two types of microcapillary are available: both are lengths of fused silica capillary externally coated with polyimide, and with two windows at fixed positions. Capillaries are supplied uncoated internally for general use. An alternative is with an internal coating of hydroxypropylcellulose, for samples where sticking to the capillary wall may be an intractable experimental issue.

Vials and vial caps

Sample handling and introduction

Image

Two types of vials are available for use with Viscosizer TD: small vials containing up to 250µl of sample, and large vials accommodating up to 2ml (for buffers, cleaning solutions and waste). Specific vial caps are used for inlet vials and outlet (waste) vials; inlet vial caps have an additional pressure seal to ensure that the required injection pressure can be achieved and to reduce sample evaporation.

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