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ELISA Detection of HBsAg


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Introduction

Hepatitis B or Serum Hepatitis is one of the most common infectious diseases in the world and has become a global public health problem. It is caused by Hepatitis B virus (HBV), which is a prototype of Hepadnaviridae family. The complete virus particle known as Dane particle has an outer envelope composed of HBsAg that surrounds a nucleocapsid or core.

The inner core of HBV contains a single molecule of partially double stranded DNA, core protein (HBcAg), HBeAg and DNA dependent polymerase. HBV is transmitted by infected blood, blood products, body fluids (viz.semen, vaginal fluid) and from infected mother to offsprings. A variety of tests are available for detection of viral antigen or host anti-viral antibodies eg. HBsAg, anti-HBsAg antibodies, anti-HBc antibodies.


Amongst these, HBsAg is most reliable marker, as it appears first usually 6-8 weeks after infection with HBV and before any change in ALT level. In 1965, Blumberg and his associates discovered Hepatitis B surface antigen (HBsAg) which was a significant breakthrough in understanding of Serum Hepatitis.  

Principle

The test is based on solid phase microplate direct ELISA (sandwich ELISA) technique


The Microwells are coated with mouse monoclonal anti-HBsAg antibodies [ |-( ].

When patient’s sample is added, if HBsAg [ O ] is present in the sample, it gets bound to    immobilized anti-HBsAg antibodies. 

After removal of non-specific antibodies, peroxidase labelled anti-HBsAg antibodies [ )-HPR] are added, which binds with immobilised antibody-antigen complex. 


After incubation and washing, TMB substrate is added, which gives blue coloured product due to enzymatic activity. In absence of HBsAg, the colour will not change from its original pink colour.                  

The reaction is stopped by addition of stopping reagent, which turns the blue colour to end point yellow colour. In negative test, original pink colour as seen in the above step will now become colourless.

The absorbance of yellow colour is directly proportional to the concentration of HBsAg present in patient sample. It is measured by microwell plate reader having 450 nm as primary filter and 630 nm as reference filter. 

Requirements

  1. Reagent 1 (Sample Diluent)
  2. Reagent 2 (Conjugate)
  3. Reagent 2A (Conjugate stabilizer)
  4. Reagent 3 (Washing Buffer) 
  5. Reagent 4 (Negative Control)
  6. Reagent 5 (Positive Control)
  7. Reagent 6 (Colour Reagent) 
  8. Reagent 7 (Stopping Solution)
  9. Reagent 8 (Microwell Strips)
  10. Distilled or deionized water
  11. Variable micropipettes and multichannel pipette with appropriate disposable tips
  12. Measuring cylinder 100 mL
  13. Timer
  14. 37oC incubator
  15. Disposable absorbent pads or towels
  16. Device for rapid delivery of washing solution automatic dispensing syringe or equivalent
  17. Biochromatic microwell plates reader with 450nm and 630nm filter .
  18. ELISA shaker (optional)      

Procedure

Bring all the reagents of the kit to room temperature except Colour reagent and Conjugate. Dilute the concentrated Wash buffer.

  1. Dispense 100 µL of reagent 1 (Sample Diluent) to all the required number of wells except, 1A (blank well). 
  2. Add 10 µL of reagent 4 (Negative Control) reagent 5 (Positive Control) and samples to the respective wells.
  3. Incubate for 60 minutes at room temperature (37oC).
  4. Decant & wash the wells 5 times with diluted reagent 3 (Wash Buffer).
  5. Add 50 µL of reagent 2A (Conjugate stabiliser) and then 100 µL of reagent 2 (Conjugate) to all the wells except1A. 
  6. Incubate for 30 minutes at (37oC).
  7. Repeat the washing step no 4.
  8. Add 100 µL of reagent 6 (Colour Reagent) to each well.
  9. Incubate for 30 minutes at room temperature in dark.
  10. Add 100 µL of reagent 7 (Stopping Solution) to each well.
  11. Read the absorbance at 450+630 nm within 30 minutes after blanking with 1A well


Result


Reference

HEPALISA Test Kit: Microwell ELISA Test for the Detection of Hepatitis B Surface Antigen (HBsAg) in Human Serum/ Plasma

Shah, K., & Maghsoudlou, P. (2016). Enzyme-linked immunosorbent assay (ELISA): the basics. British journal of hospital medicine, 77(7), C98-C101.

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