CASY Cell Counter + Analyzer

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Comprehensive Cell Status Monitoring label-free, with outstanding precision and reproducibility (Cell Concentration + Cell Number + Cell Viability + Cell Volume )

  • The international Gold Standard* for label-free, non-invasive determination of cell number and viability.
  • CASY® Cell Counter works fully automated. Stains or dyes become obsolete – no  interferences from dyes, combined with minimum work effort.
  • Flexible and reliable cell analyzer, perfect reproducibility and robustness into one instrument, combined with a life time calibration and nearly zero maintenance.
  • Well proven system for fast, cost effective and yet simple to operate multi-parameter analysis of cell cultures.

 

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CASY® system determines the following parameters within seconds only:

  • Cell Number– Total cell count and live cell count
  • Cell Viability– Non-invasive counting, no dyes or stains used
  • Cell Size Distribution– High resolution and large dynamic measuring range
  • Cell Volume– Calculation of the average cell diameter
  • Cell Aggregation– Measure and calculates cell aggregation factor, automatic correction possible
  • Cell Debris– Quality control of cell culture solutions

 

CASY tracks all relevant aspects of the status of your cell cultures:

  • Label-free cell status, instantly.
  • Within seconds, measurement is performed non-invasively without using distorting dyes.
  • Statistically relevant data
  • Analysis of more than 4,000 cells per run enables  statistically significant results.
  • Get the full picture
  • CASY quantifies all relevant parameters of cell cultures including  cell viability and aggregation – at extremely low running costs
Feature Benefit
The sensor is directly immersed into the sample solution Grants no errors, no losses of cell Material by sedimentation , correct analysis of cell aggregates
Dye-free, non-invasive measurement of cell number and viability Accurate results for viability of sensitive and even partially damaged cell suspensions, free nuclei are determined as dead cells
Large dynamic measuring range Every single analysis covers the full range from Debris, to dead and live cells and includes large aggregates of living cells
High resolution size distribution dis-played as histogram with over 400 size channels All results at one single glance
Aggregation factor calculated from particle volume Correct results also from highly aggregative cell types
No single-use counting chambers or dedicated slides necessary Lowest possible cost/analysis ratio
Rapid Measurement – from only 10 sec to 1 min per measurement Immediate results, no risk of measurement artefacts from sedimentation while waiting in an autosampler

 

CASY Cell Counters and Analysers combine all advantages of non-invasive, dye-free cell analysis with an ultra-durable hardware, easy to operate and nearly maintenance free. Inter-system and inter-laboratory reproducibility is guaranteed. By use of three different counting capillaries a size range from as low as 0.8 µm to 120 µm, all cell types from algae, bacteria, yeast to prokaryotic and eukaryotic cells can be analysed with one system only.

  • Certified, traceable life time calibration
  • Automatic electronic surveillance of the counting capillary, no manual control necessary
  • Integrated QA system checks for all possibly critical deviations and measuring errors
  • GLP/GMP compliant: IQ, OQ, PQ (CASY TT and TTC)
  • 21 CFR Part 11 compliant (CASY TTC)
  • Based on reference method ISO 13319
  • No system fan, perfect for clean room installation

Principle of Function

  • The CASY® technology uses the current exclusion method: particles and cells passing through a defined size pore generate a resistance signal varying with their size and conductivity. Live cells with a polarized membrane generate a high resistance signal, whereas dying or dead cells display a much lower resistance due to their depolarized or fully disrupted cell membrane. The signal of one cell passing the pore is resolved with a high frequency of 1 MHz, and hence the area under the curve = the Integral can easily be calculated, the integral being the only parameter directly proportional to the cell size. As the integral is seriously different with live cells, dead cells and debris, the particle sizes and their distribution can be recorded and analyzed very precisely. One additional benefit is the large dynamic measuring range (e.g. 150µ capillary: 3.2 – 120 µm = from debris via dead/live cells to cell aggregates of several 100 cells size), which cannot be reached by any other method of cell size analysis. By limiting the number of count events, CASY® works without any mathematical approximations to deal with multiple particles passing the capillary simultaneously, every cell or particle is analyzed as a single count event.

How it Works.

CASY’s measuring principle to discriminate between debris, dead and viable cells – and how it is graphically represented during measurement (Mixture of chondrocyte primary culture).

Viable / dead cells differentiation

  • CASY quantifies cells and particles passing a measuring pore exposed to a low voltage electrical field. Based on a cells size and conductivity, a resistance signal is generated and recorded. Living cells generate high resistance signals due to their intact membrane structure. Dying or dead cells cause much lower resistance due to their increased membrane permeability: they are measured by the size of their cell nuclei.

Cell viability

  • Furthermore, cell viability is determined by automatically quantitatively comparing viable cells with dead cells, the latter being represented by the size of their nuclei in the measurement chart.

Maximum information from flow-through measurement

  • Objects passing the measuring pore are scanned with a high frequency of 1 MHz. This allows a precise recording of cell number and cell volume.

Huge dynamic measuring range

  • 1 MHz sampled Pulse Area Analysis leads to an unsurpassed dynamic measuring range visualizing the whole range of particles from cell debris to large cellular aggregates in a single measurement

Get the full picture of your cells

  • In a simple, fast and dye-free measurement, the huge dynamic measuring range provides you with all aspects of the current status of your cell culture: Monitor cell debris, distinguish viable cells from dead cells, and readily observe cell clusters/ aggregates – all at a single glance.

Biomass-determination or aggregates? CASY delivers accurate volumes

  • High-frequency scanning of objects and the high dynamic measuring range, enable CASY to precisely measure volumes of cells or objects. Thus, cell aggregates and the entire biomass content of each sample are immediately available.

Accurate total cell count includes aggregates

  • Mathematically breaking down aggregates into single cells, CASY optionally counts all cells hidden in aggregates – and thus provides an accurate total cell count.

No limits. CASY measures cell lines, primary cells, bacteria, yeast, algae, parasites … – you name it

  • With a detection range of 0.7 – 120 µm, CASY measures all types of mammalian cells and stem cells, as well as bacteria, yeast, algae, parasites, pollen, sperm and more. Any particle in the size range might be measurable – and a lot of various samples have been readily measured.

All Important Markers of Cell Condition + In a Single Measurement + In Seconds

Counting Cells in just Seconds

  • Cells suspended in CASYton, a conductive isotonic buffer solution, are drawn through a measuring pore. This pore is defined in size and housed inside the capillary which separates two platinum electrodes, the inner and outer electrode. Here, a low voltage field is cycling with 1 MHz. Each cell or particle passing the measuring pore generates an individual electrical pulse by displacing buffer electrolyte in the measuring pore. This pulse is measured as a cell count.

Cell Viability

  • Keep Tabs on Membrane Degradation As CASY takes the whole pulse area into account, including amplitude and pulse width, high resolution measurements are enabled, allowing to detect slightest changes of the cell membrane’s electrical properties. The permeable membrane of dying and dead cells thus allows to identify dead cells by a change in electrical resistance, finally indicating the size of the nucleus.

Accurate Cell Volume

  • The combination of amplitude and width of the electrical pulse is proportional to the individual volume of the cell or particle passing the pore. Thus, cell volume can be directly deduced from the change in electrical resistance.

Biomass & Cell Aggregation

  • The True Cell Count Biomass concentration and cell aggregation are essential parameters in any cell culture- and fermentation setting. CASY’s measuring principle, including accurate cell volume determination, enables CASY to calculate aggregate volumes. This delivers extremely precise and reliable information on biomass content and aggregation status of your cells in culture. Furthermore, by taking account of cells hidden in aggregates, the true cell count is determined. Thereby drastically improving the accuracy of counting results.

Cell Debris and the »Comfort Zone« of Your Cells

  • Cellular debris may dramatically influence cell-based assays and its absence is an excellent indicator verifying that your cells are in the »comfort zone«. The huge dynamic size range of each CASY measurement provides you with a significant criterion for the usability of the cells in any critical follow-up experiment – at a single glance. And it does so quickly: typical measurement time of mammalian cells is around 10 seconds.

CASY® Modell TTC – Cell Counter and Analyzer System with “embedded” Computer System (21 CFR 11/GXP)

Cell Counter + Analyzer for the high end research lab with extended demand for reproducibility, sample throughput, documentation of results and for research areas that work under GLP/GMP regulations.

Areas of Application

  • Reliable multi-parameter QA on cell cultures at lowest cost
  • Simultaneous determination of cell count, size distribution, cell volume, aggregation and cell debris in less than 10 seconds, avoiding any dyes
  • Need for highest accuracy and reproducibility, which dye-based methods and systems with autosampler (= longer waiting times) cannot achieve
  • Laboratories with several users and different applications
  • Need for highest quality documentation and evaluation of results
  • Controlled work environment and SOPs that require compliance with GLP/GMP

 

Three different capillary sizes enable a measuring range reaching from 0.7 µm up to 120 µm:

Capillary     Ø [µm] Size Range   [µm] Application Areas
45 0.7 – 30 Debris, Bacteria, Spores
60 1.2 – 40 Yeast, Algae, Erythrocytes, Pollen, Plankton, Parasites, Sperms
150 3.2 – 120 Cell lines, Primary mammalian cells, white blood cells, stem cells, fish cells, large algae and protozoa, plant cells and protoplasts

For CASY TTC a large and continuously growing library of reference data is available. The required software CASY®datadoc comes with every system.

 

CASY: Budget-friendly Benefits to Your Cell Analysis

  • Dye-free, non-invasive determination of the cell activity via ECE® (electric current exclusion method): produces correct data on viability and vitality even for very sensitive cells and partly damaged cells
  • Aggregation factor calculation based on particle volume: Correct cell count even if large cell clusters are present
  • No single use consumables like counting slides or counting capillaries: very low cost per count

 

Designed for the Demanding Quality Control

CASY TTC was developed especially to meet the requirements in QA of cell culture in research labs as well as in process development and production control. It fulfills the high standards of documentation quality and comprehensive data evaluation needs and was designed to meet the special requirements of labs with a very high number of users and many different applications.

  • A very comfortable windows-based user interface, menus driven and equipped with a full size computer monitor for displaying results and the high res size distribution histograms (1024 size channels)
  • Unlimited storage of cell line/application -specific set-ups
  • LAN interface to connect the systems to data storage and network printers
  • Full flexibility for data evaluation: either directly on the embedded PC or externally using CASY®datadoc software
  • Full GLP/GMP/21 CFR 11 compliance, 3 user levels (guest, user, admin), checksum-secured file formats, electronic signatures and audit trails
  • Simple validation of Analyzer system and embedded PC (IQ/OQ)
  • Dimensions (HxWxD): 65 cm x 41 cm x 39 cm – w/o keyboard and mouse

 

CASY® – Technical Overview

Measuring Technique CASY TT CASY TTC
measuring principle capillary particle counter with pulse area analysis
Parameters determined Cell size distribution, cell count, cell concentration, cell viability, cell aggregation, cell debris, cell volume (peak), average cell diameter
Determination of size dsitribution Digital pulse count/area analysis, 1 Million data points per second, equals several 100 data points per cell
Viability measurement Electrical Current Exclusion (ECE®)
Dye-free, non-invasive determination of the membrane permeability
Aggregation factor determination Based on the volume of the single free cell, resolves clusters from 2 up to several hundred cells
Concentration determination Counting volume controlled opto-electronically, maintenance free, calibrated for life time

 

Performance Data CASY TT CASY TTC
Reproducibility Typical Std. Deviation = +/- square root (number of counted particles) e.g.: 10 000 cells = +/- 2%
Sensitivity >= 100 Particles/ml
Measuring Range 0,7 – 120µm (with all 3 capillaries)
Dynamic Ranges 1 : 70 000 in volume corresponding to 1 : 40 in diameter
Resolution of
size distribution
512 000 channels, linearized by volume
Resolution of
size distribution display
400 channels, linearized by volume 1024 channels, linearized by diameter
Typical measuring times 150µm capillary: 10 sec., 60µm capillary: 25 sec, 45µm capillary: 45sec
Typical sample volume required 5 – 100µl
Storage capacity of cell specific setups 20 unlimited
Cleanroom Qualification No fan, certified for cleanroom class A

 

Quality Assurance CASY TT CASY TTC
Self-Test Checks all relevant parameters upon power-on (POST) and before every measurement
Sensor control Continuous electronic monitoring of capillary
System Self-Protect Automatic recognition of operating errors, error message display
Calibration Calibration certified ex works, life time calibration,
guarantees identical results from all CASY systems
QC Standards GLP/GMP compliant, signature required GLP/GMP compliant and meeting 21 CFR 11 (electronic signature)
Audit Trails no yes – full independent audit trails recorded for: System-, File- and Error events

 

Communication CASY TT CASY TTC
Data Entry –
Results display
Separate keypad with graphical display and 13 keys Menu driven software, Win CE®, color screen and embedded PC
Data format ASCII Binary, checksum protection
Data export Structured ASCII text, for import into any other software (e. g. MS Excel)
Interfaces Data: 2 x RS 232 (DB9),
Printer: Parallel Centronics (DB25)
Raw data: 2 x RS 232 (DB9)
Mouse, Keyboard: USB
Printer: USB, LAN
File storage: CF-Card, LAN
PC-Software CASYexcell (Viewer) CASYdatadoc (Editor)

CASY® Modell TT – Cell Counter and Analyzer System

Cell Counter + Analyzer for research labs with high sample throughput and/or GLP certification demanding highest degree of reproducibility

Areas of Application

  • Reliable multi-parameter QA on cell cultures at lowest cost
  • Simultaneous determination of cell count, size distribution, cell volume, aggregation and cell debris in less than 10 seconds, no dyes used
  • Need for highest accuracy and reproducibility, which dye-based methods and systems with autosampler = longer waiting times cannot achieve

 

Three different capillary sizes enable a measuring range reaching from 0.7 µm up to 120 µm:

Capillary Ø [µm] Size range [µm] Application areas
45 0,7 – 30 Debris, Bacteria, Spores
60 1,2 – 40 Yeast, Algae, Erythrocytes, Pollen, Plankton, Parasites, Sperms
150 3,2 – 120 Cell lines, Primary mammalian cells, white blood cells, stem cells, fish cells, large algae and protozoa, plant cells and protoplasts

For the CASY® TT a large and continuously growing library of reference data is available. The required software CASY®excell comes with every system.

 

CASY: Budget-friendly Benefits to Your Cell Analysis

  • Dye-free, non-invasive determination of the cell activity via ECE® (electric current exclusion method): produces correct data on viability and vitality even for very sensitive cells and partly damaged cells
  • Aggregation factor calculation based on particle volume: Correct cell count even if large cell clusters are present
  • No single use consumables like counting slides or counting capillaries: very low cost per single count experiment

 

Designed for the Demanding Quality Control

The CASY TT was developed primarily for use in cell culture research in universities and in pharmaceutical and biotech research companies and comes as a stand-alone unit. As such the space requirements are very small and it fits into even the smallest lab. It offers the following key features:

  • Very easy to operate, separate control panel with graphical display and plastic foil keypad
  • Display of size distribution histogram and key results on the same screen mask
  • Stores up to 20 parameter sets for different cell types
  • Dimensions (HxWxD): 39 cm x 31 cm x 39 cm, excl. keypad
  • Results can be stored externally by using the CASYworX software; requires MS Excel

 

CASY – Technical Overview

Measuring Technique CASY TT CASY TTC
measuring principle capillary particle counter with pulse area analysis
Parameters determined Cell size distribution, cell count, cell concentration, cell viability, cell aggregation, cell debris, cell volume (peak), average cell diameter
Determination of size dsitribution Digital pulse count/area analysis, 1 Million data points per second, equals several 100 data points per cell
Viability measurement Electrical Current Exclusion (ECE®)
Dye-free, non-invasive determination of the membrane permeability
Aggregation factor determination Based on the volume of the single free cell, resolves clusters from 2 up to several hundred cells
Concentration determination Counting volume controlled opto-electronically, maintenance free, calibrated for life time

 

Performance Data CASY TT CASY TTC
Reproducibility Typical Std. Deviation = +/- square root (number of counted particles) e.g.: 10 000 cells = +/- 2%
Sensitivity >= 100 Particles/ml
Measuring Range 0,7 – 120µm (with all 3 capillaries)
Dynamic Ranges 1 : 70 000 in volume corresponding to 1 : 40 in diameter
Resolution of
size distribution
512 000 channels, linearized by volume
Resolution of
size distribution display
400 channels, linearized by volume 1024 channels, linearized by diameter
Typical measuring times 150µm capillary: 10 sec., 60µm capillary: 25 sec, 45µm capillary: 45sec
Typical sample volume required 5 – 100µl
Storage capacity of cell specific setups 20 unlimited
Cleanroom Qualification No fan, certified for cleanroom class A

 

Quality Assurance CASY TT CASY TTC
Self-Test Checks all relevant parameters upon power-on (POST) and before every measurement
Sensor control Continuous electronic monitoring of capillary
System Self-Protect Automatic recognition of operating errors, error message display
Calibration Calibration certified ex works, life time calibration,
guarantees identical results from all CASY systems
QC Standards GLP/GMP compliant, signature required GLP/GMP compliant and meeting 21 CFR 11 (electronic signature)
Audit Trails no yes – full independent audit trails recorded for: System-, File- and Error events

 

Communication CASY TT CASY TTC
Data Entry –
Results display
Separate keypad with graphical display and 13 keys Menu driven software, Win CE®, color screen and embedded PC
Data format ASCII Binary, checksum protection
Data export Structured ASCII text, for import into any other software (e. g. MS Excel)
Interfaces Data: 2 x RS 232 (DB9),
Printer: Parallel Centronics (DB25)
Raw data: 2 x RS 232 (DB9)
Mouse, Keyboard: USB
Printer: USB, LAN
File storage: CF-Card, LAN
PC-Software CASYexcell (Viewer)

CASYworX (View & Edit)

CASYdatadoc (Editor)

 

Measurement principle Electronic pulse area analysis with 1 million measurements   per second acc. to ISO 13319
Viability determination Electrical Current Exclusion (ECE)
Dynamic range in volume > 1:70,000

in diameter > 1:40

Measured size channels 512,000
Displayed size channels 1,024 (TTC); 400 (TT)
Measurement range 0.7–120 μm
Volume Resolution 1 in 512,000
Typical analysis time 10 seconds
Typical sample volume 5 –100 μl
Interfaces TT: RS 232 (2xDB9), Parallel (DB25),

TTC: RS 232 (2xDB9),   TCP/IP (RJ45), USB (3x),Compact flash memory card

 

CASY TTC

Cell count, cell volume, cell debris, cell viability and aggregation in less than 10 second

  • unlimited cell specific setups
  • menu-driven software, Win CE embedded PC, color screen, keypad & mouse
  • binary data format with checksum protection
  • CASYdatadoc PC software
  • GLP/GMP compliant
  • 21 CFR Part 11 compliant
  • full audit trails
  • 3 different user levels
  • electronic signature

 

CASY TT

Cell count, cell volume, cell debris, cell viability and aggregation in less than 10 seconds

  • 20 cell specific setups
  • separate control panel  with graphical display
  • ASCII data format
  • CASYworX PC software
  • GLP compliant