Magnetic Bead DNA Extraction Protocol

ENTM201L - General Entomology Laboratory | UC Riverside

Magnetic Bead DNA Extraction Protocol

Protocol Overview

This protocol uses magnetic beads to extract high molecular weight genomic DNA from mosquito specimens. The magnetic bead method is ideal for long-read sequencing applications and produces DNA fragments ranging from 50-150 kb.


Materials and Equipment

Required Equipment

Required Reagents

BioDynami Genomic DNA Extraction Kit (Magnetic Beads) containing:

  • Magnetic beads suspension
  • Lysis Buffer (LB)
  • Proteinase K
  • Binding Buffer (BB)
  • Wash Buffer 1 (W1)
  • Wash Buffer 2 (W2)
  • Elution Buffer (EB)

Sample Requirements

Safety Notes

  • Wear gloves and lab coat at all times
  • Lysis buffer contains guanidine salts - avoid contact with bleach
  • Dispose of mosquito remains in biohazard waste
  • Clean work area with 70% ethanol after completion

Protocol Steps

Part 1: Sample Preparation (15 minutes)

Step 1: Label Tubes

1 Label a 1.5 mL microcentrifuge tube with sample ID

2 Record sample information in lab notebook

Step 2: Prepare Mosquito Sample

1 If preserved in ethanol, air dry for 5 minutes

2 Place single mosquito in labeled tube

3 Add 20 µL of Proteinase K to the tube


Part 2: Tissue Lysis (45 minutes)

Step 3: Add Lysis Buffer

1 Add 200 µL Lysis Buffer (LB)

2 Use clean pestle to grind tissue thoroughly

3 Ensure complete homogenization (no visible tissue pieces)

Pro Tip

Thorough grinding is critical for high DNA yield. Grind until no visible tissue pieces remain.

Step 4: Incubate for Digestion

1 Vortex for 15 seconds

2 Incubate at 56°C for 30 minutes

3 Vortex briefly every 10 minutes during incubation

What's Happening?

Proteinase K digests proteins at 56°C, releasing DNA from cellular structures. Periodic vortexing ensures complete tissue breakdown.


Part 3: DNA Binding to Magnetic Beads (20 minutes)

Step 5: Prepare Magnetic Beads

1 Vortex magnetic bead stock solution for 30 seconds

2 Add 20 µL magnetic beads to the lysate

3 Add 200 µL Binding Buffer (BB)

Important

Always vortex magnetic beads immediately before use. Beads settle quickly and must be evenly suspended.

Step 6: Bind DNA to Beads

1 Vortex thoroughly for 10 seconds

2 Incubate at room temperature for 10 minutes

3 Mix by inverting tube every 2 minutes

What's Happening?

The Binding Buffer creates conditions for DNA to adhere to the magnetic bead surface. Periodic mixing ensures all DNA molecules contact the beads.


Part 4: Magnetic Separation and Washing (30 minutes)

Step 7: First Magnetic Separation

1 Place tube on magnetic rack for 2 minutes

2 Wait until solution clears and beads collect at magnet

3 Carefully pipette off and discard supernatant

Critical

DO NOT disturb the bead pellet when removing supernatant. Keep tube on magnetic rack and pipette from the side opposite the magnet.

Step 8: First Wash

1 Remove tube from magnetic rack

2 Add 500 µL Wash Buffer 1 (W1)

3 Vortex for 5 seconds to resuspend beads

4 Place on magnetic rack for 1 minute

5 Remove and discard supernatant

Purpose

Wash Buffer 1 removes proteins and cellular debris while DNA remains bound to magnetic beads.

Step 9: Second Wash

1 Add 500 µL Wash Buffer 2 (W2)

2 Vortex for 5 seconds

3 Place on magnetic rack for 1 minute

4 Remove and discard supernatant

Step 10: Third Wash

1 Repeat step 9 with fresh Wash Buffer 2

2 After removing supernatant, briefly spin tube

3 Place back on magnetic rack

4 Remove any residual wash buffer with P20 pipette

Pro Tip

Removing all wash buffer is critical. Residual ethanol will inhibit downstream applications. Use a P20 pipette to remove the last few microliters.


Part 5: DNA Elution (15 minutes)

Step 11: Dry Magnetic Beads

1 Keep tube on magnetic rack

2 Air dry beads for 5 minutes (cap open)

3 Beads should appear matte, not shiny

Critical

Do not over-dry beads (>10 minutes). Over-dried beads are difficult to resuspend and reduce DNA recovery.

Step 12: Elute DNA

1 Remove tube from magnetic rack

2 Add 50 µL Elution Buffer (pre-warmed to 65°C)

3 Vortex vigorously for 10 seconds

4 Incubate at 65°C for 5 minutes

What's Happening?

Warm, low-salt Elution Buffer releases DNA from the magnetic beads. Elevated temperature improves DNA recovery.

Step 13: Collect Eluted DNA

1 Place tube on magnetic rack for 2 minutes

2 Transfer clear supernatant (contains DNA) to new labeled tube

3 This is your purified DNA sample

Pro Tip

When transferring eluted DNA, avoid aspirating any magnetic beads. Leave 1-2 µL behind if needed to prevent bead contamination.


Part 6: Quality Assessment (15 minutes)

Step 14: Quantify DNA

1 Measure concentration using NanoDrop or Qubit

2 Record A260/A280 and A260/A230 ratios

3 Expected yield: 1.5-2 ng/µL (typical for mosquito specimens)

Quality Metrics:

  • A260/A280 ratio: 1.8-2.0 (pure DNA)
  • A260/A230 ratio: 2.0-2.2 (no contaminants)
  • Total yield: 75-100 ng DNA (in 50 µL elution)

Step 15: Store DNA

1 Store at -20°C for short term (weeks)

2 Store at -80°C for long term (months/years)

3 Label clearly with date, sample ID, and concentration


Expected Results

Typical Yields (from mosquito specimens)

Parameter Expected Value
Concentration 1.5-2 ng/µL
Total yield 75-100 ng DNA (in 50 µL elution)
A260/A280 ratio 1.8-2.0 (pure DNA)
A260/A230 ratio 2.0-2.2 (no contaminants)

Comparison with Column Method

Parameter Magnetic Beads Spin Columns
Time ~2 hours ~1.5 hours
Yield Higher Moderate
Purity Excellent Good
Hands-on time Less More
Automation Possible Limited
Cost per sample Higher Lower

Troubleshooting

Low DNA Yield

  • Incomplete lysis: Extend incubation time or add more Proteinase K
  • Bead loss during washing: Be more careful when removing supernatant
  • Incomplete elution: Ensure beads are fully resuspended in elution buffer

Poor DNA Quality (Low A260/A280)

  • Protein contamination: Add additional wash steps
  • Incomplete drying: Ensure all ethanol is removed before elution

No DNA Detected

  • Sample degradation: Use fresh samples or properly preserved specimens
  • Beads not functioning: Check expiration date and storage conditions
  • Elution buffer pH: Ensure pH is between 8.0-8.5

Key Takeaways

Summary

  • Magnetic bead extraction produces high molecular weight DNA (50-150 kb)
  • Method is ideal for long-read sequencing applications
  • Critical steps: thorough grinding, complete washing, gentle elution
  • Typical yield from single mosquito: 75-100 ng total DNA
  • DNA quality should be A260/A280 = 1.8-2.0

Notes

  • This protocol is optimized for single mosquito specimens
  • For pooled samples, scale up reagent volumes proportionally
  • Magnetic beads can be regenerated for cost savings (see manufacturer's protocol)