1. the perfect ESR system

2. What is ESR?
The Erythrocyte Sedimentation Rate (ESR) is an easy, inexpensive, nonspecific laboratory test that in conjunction with the patient’s clinical history and physical examination findings, serves as a very useful “sickness index”.
Has been often referred to as “the laboratory equivalent to taking the temperature or measuring the blood pressure”.
Helpful in revealing inflammatory activity and in monitoring the progress of conditions associated with acute and chronic inflammation, including infections, cancers, and autoimmune diseases.
Useful in evaluating patients with unexplained symptoms, when infectious diseases are suspected and when a specific diagnosis is not available effectively using other tests.
Provides particularly valuable information in conditions such as temporal arteritis, polymyalgia rheumatica, giant cells arteritis, inflammatory arthropaties etc.

3. How the ESR test is performed
Since it was introduced at the beginning of the 20th century1 the ESR test has been performed in essentially the same way - measuring the distance at which the red cells, under the effect of gravity, will sediment over a certain period of time.
The principle of the test is that red blood cells or erythrocytes in the presence of inflammation tend to aggregate and to form clumps and to settle more quickly.
1Biernacki 1897; Fahraeus 1918

4. Physiology of ESR
In response to inflammatory states occurring during infection, injury, surgery, trauma, and all causes of tissue necrosis, there is a marked increase in the level of acute phase reactant proteins. These proteins include α1-acid glycoprotein, haptoglobin, α1-antitrypsin, ceruloplasmin, complement proteins, fibrinogen, C-reactive protein (CRP), and immunoglobulins. The increased level of the acute phase proteins alter the electrical balance between red cells and proteins which results in the aggregation of erythrocytes in a process called rouleaux formation. This phase of “rouleaux formation” is the first and most critical phase of the ESR. Rouleaux formation_video

5. Physiology of ESR
In fact, the faster and more intense is the aggregation of the red cells, the bigger are the rouleaux and, consequently, according to Stokes’ laws, the faster the sedimentation
This is best illustrated by plotting the descent of the red cells during the performance of the ESR according to the traditional methods such as the Westergren. The plot will show that the sedimentation of the red cells takes place according to a sigmoid curve with three distinct phases:
Phase 1: Lag Phase
This is the initial phase during which individual erythrocytes aggregate to form rouleaux and the sedimentation begins
Phase 2: Decantation Phase
The plasma /erythrocyte interface falls more rapidly and the settling rate is more constant
Phase 3: Packing Phase
The red cells aggregates pile up at the bottom of the tube or container. The sedimentation slows down as a result of the interference of the accumulated red blood cells

6. Physiology of ESR (cont.)
The phase of red cell aggregation or “rouleaux formation”, therefore, is the most critical phase of the sedimentation.
The distance that the red cells travel downward while settling (mm/hr) is dependent upon the intensity of the aggregation and the size of the aggregates.
In essence, then, the ESR test as performed with the traditional manual and automated methods, is an indirect way to measure the “red cell aggregation”.

7. Current ESR testing methods
Through the years, there have been many manual, automated and semi-automated methods which have been utilized to measure the ESR. All these methods consist of visually or electronically recording the distance at which red cells, under the effect of gravity, sediment in a certain period of time in a particular testing environment. In general, all gravitation-based methods, are “critically” affected by a multiplicity of factors and testing variables which need to be strictly controlled to avoid unreliable results. In an effort to standardize the ESR testing procedure, International Committee for Standards in Hematology (ICSH) and the Clinical Laboratory Standards Institute (CLSI) have defined an “Approved Standard” which should serve as guideline for the proper performance of the test.

8. Limitations of Manual methods
Manual systems consist of transferring the blood specimen from a primary collection tube into a calibrated pipette and of visually recording the distance at which the red cells sediment. These systems have the following limitations:
They are cumbersome to perform
They require handling of large blood samples
They are subject to a variety of technical limitation such as: subjective reading of the sedimentation level, environmental variables, improper mixing of the sample, possibility of mislabeling the test pipette with consequent confusion on the identity of the patient, need to read exactly at the precise moment (after 1hour) the level of sedimentation of the red cell, errors in the transcription of the test results, inadequate quality control

9. Limitations of Semi-automated methods
Automated Systems essentially consist of either (a) Transferring the blood specimen collected in a primary tube into a special ESR cuvette; or (b) Utilizing the special cuvette as the primary collection tube. The current automated systems have the following limitations:
Transfer of blood is required into the test ESR cuvette
The ESR cuvette can be utilized as a primary collection tube, in which case the phlebotomist is required to draw an additional blood collection tube - an obvious inconvenience for the patient and for the laboratory
Inadequate and/or not-uniform mixing of the blood sample
Batch testing of samples - does not provide the necessary flexibility in a normal hospital testing
Blood sample required for testing is large (1mL- 1.2mL volume of blood) and the testing time is still long (30+ minutes)
They utilize “multiple testing sensors” which in effect represent “multiple analyzers” with consequent invalid and inadequate Quality Control procedures. Verifying the function of each sensor with every QC run would be cost and time prohibitive for labs.

10. Perfect ESR results in seconds
The iSED® Automated Sedimentation Rate analyzer has been developed:
To offer the clinician an ESR test which is consistently accurate and precise
To offer the clinician the possibility of testing with micro-volumes of blood
To transform the most cumbersome lab test into the simplest and easiest to perform
To offer the technologist a fully automated, random-access and walk-away solution which is easily integrated into the routine of the lab

11. Perfect ESR results in seconds
The technical innovation of iSED® consists of measuring directly the intensity of the red cell aggregation which is responsible for the ESR.
In essence, while the traditional ESR methodologies measure the aggregation of the red blood cells indirectly, the iSED measures it directly and expresses the values in mm/hr.
By virtue of its technology, the iSED produces ESR results within 20 seconds without the variables which are commonly associated with traditional ESR testing, the most important of which is the hematocrit.

12. Increased Productivity
Works directly off the primary EDTA tube
No disposables
No sample splitting
No more duplicate tubes
Minimal sample requirement
100 microliters aspirated for testing
500 microliters volume requirement in standard tubes
250 microliters sample in BD MAP Microtainers
No more QNS!
Continuous Feed
No batching required
Random access
Immediate tube return

13. Increased Efficiency Fully Automated Reliable and Accurate
Internal barcode reader
On-board automated mixer
Internal printer
LIS capability
Reliable and Accurate
Single reading cell
100% QC of analyzer
Barcoded Seditrol® Quality Control for ESR
Online QC Data Management and peer data

14. Improved ESR testing with iSED®
Problem
iSED® Solution
Sample Contamination
Direct, through-stopper reading from EDTA tube
Patient Identification
Internal barcode reader positively identifies the patient sample for analysis
QNS
Min. tube volume 500μL; requires only 100μL for analysis; compatible with BD MAP Microtainer
Temperature Variation
Automated temperature correction
Timing of Reading
Automated reading by analyzer
Sample Positioning
All readings done in a controlled chamber
Improper Mixing
Automated mixing according to CLSI standard
Falsely elevated results due to low HCT
Rate and severity of aggregation being measured directly – less affected by variations in hematocrit and MCV

15. No more QNS Continuous operation On-board mixing Fully Automated
PRIMARY
Internal barcode reader
EDTA
Internal printer
Tube
Random access
On-board mixing
Continuous operation
100 microliter sample
No more QNS
20 second results

16. ALCOR Scientific Inc.
20 Thurber Boulevard
Smithfield, RI 02917