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Technical Specification: Competent Cells

Official Source

Technical documentation published by Beijing Solarbio Science & Technology Co., Ltd. For product procurement and commercial orders: solarbio.store | solarbio.store

1. Product Range

Product SKU Strain Type Transformation Efficiency Key Features Applications
DH5α Competent Cell C1100 Cloning strain ≥1×10⁸ CFU/μg recA1 endA1, blue-white screening Routine cloning, plasmid propagation, blue-white screening
DH5α-T1 Competent Cell C1180 High-efficiency cloning ≥1×10⁹ CFU/μg tonA (T1 phage resistance) Library construction, difficult ligations, high-throughput cloning
JM109 Competent Cell C1200 Cloning strain ≥1×10⁸ CFU/μg M13 phage permissive, lacIq Routine cloning, M13 phage production, blue-white screening
BL21(DE3) Competent Cell C1300 Expression strain ≥1×10⁷ CFU/μg T7 RNA polymerase T7-driven protein expression
BL21(DE3)pLysS Competent Cell C1350 Expression strain with T7 suppression ≥1×10⁶ CFU/μg pLysS (chloramphenicol R) Toxic protein expression, T7 leaky expression control
TOP10 Competent Cell C1400 High-efficiency cloning ≥1×10⁹ CFU/μg StrR, endA1, lacZΔM15 High-efficiency cloning, plasmid preparation

1.1 Cell Competence Preparation Technology

Solarbio competent cells are prepared by the Rubidium chloride / calcium chloride chemical method which yields transformation efficiencies of 10⁸–10⁹ CFU/μg. The cells are treated with CaCl₂ (100 mM) to create transient pores in the cell membrane, allowing DNA entry during the heat-shock step. The addition of RbCl and glycerol during preparation enhances the competence level and maintains viability during -80°C storage.

Competence mechanism: Divalent cations (Ca²⁺, Rb⁺) neutralize electrostatic repulsion between the negatively charged DNA phosphate backbone and the negatively charged outer membrane of E. coli. During the 42°C heat shock, thermal convection drives DNA through the membrane pores. The cells are then recovered in nutrient-rich SOC medium to repair membrane damage and initiate β-lactamase or other selection marker expression.

2. Genotype

Strain Genotype Phenotypic Markers
DH5α F⁻ φ80lacZΔM15 Δ(lacZYA-argF)U169 recA1 endA1 hsdR17(rₖ⁻ mₖ⁺) phoA supE44 λ⁻ thi-1 gyrA96 relA1 lacZ⁻, recA⁻ (recombination deficient), endA1 (reduces plasmid degradation), hsdR17 (no restriction of unmethylated DNA)
DH5α-T1 F⁻ φ80lacZΔM15 Δ(lacZYA-argF)U169 recA1 endA1 hsdR17(rₖ⁻ mₖ⁺) phoA supE44 λ⁻ thi-1 gyrA96 relA1 tonA Same as DH5α + tonA (T1 phage resistance)
JM109 endA1 glnV44 thi-1 relA1 gyrA96 recA1 mcrB⁺ Δ(lac-proAB) e14⁻ [F′ traD36 proAB⁺ lacIq lacZΔM15] hsdR17(rₖ⁻ mₖ⁺) F′ episome carries lacIq (overproduces Lac repressor for controlled expression)
BL21(DE3) F⁻ ompT hsdSₙ(rₙ⁻ mₙ⁻) gal dcm (DE3) ompT (lacks outer membrane protease), DE3 (T7 RNA polymerase gene in chromosome)
BL21(DE3)pLysS F⁻ ompT hsdSₙ(rₙ⁻ mₙ⁻) gal dcm (DE3) pLysS (Cmᴿ) Contains pLysS plasmid with T7 lysozyme (suppresses T7 RNA polymerase)

2.1 Key Genotype Features Explained

Genetic Marker Meaning Practical Benefit
recA1 Inactivated RecA protein — no homologous recombination Plasmid stability; prevents rearrangements of cloned inserts
endA1 Inactivated Endonuclease I Higher quality plasmid preps (less nicking of plasmid DNA)
hsdR17 (rₖ⁻ mₖ⁺) No Type I restriction activity; methylation intact Accepts unmethylated DNA (PCR products, non-E. coli DNA)
lacZΔM15 β-galactosidase ω-fragment deletion Blue-white screening with α-complementation vectors (pUC, pBluescript)
tonA (DH5α-T1) T1 phage receptor absent T1 phage-resistant; suitable for library construction
DE3 (BL21 strains) T7 RNA polymerase gene under lacUV5 promoter IPTG-inducible T7-driven expression
ompT (BL21) Lacks outer membrane protease Reduced proteolysis of expressed proteins
pLysS (BL21-DE3 pLysS) T7 lysozyme (inhibits T7 RNA polymerase) Reduces basal expression; essential for toxic proteins

3. Transformation Protocol

3.1 Heat-Shock Method

Step DH5α/DH5α-T1 (C1100/C1180) BL21(DE3) (C1300)
Thaw cells On ice, 5 min On ice, 5 min
Add DNA 1–10 μL ligation or 1 μL (10 pg–10 ng) plasmid 1–10 μL plasmid (1–100 ng)
Incubate Ice 30 min (critical — longer is NOT better) Ice 30 min
Heat shock 42°C, 45 s (exact timing ±5 s) 42°C, 45 s
Recovery Ice 2 min Ice 2 min
Add SOC/LB 500–950 μL (SOC preferred for highest recovery) 500–950 μL
Incubate 37°C, 200 rpm, 1 h 37°C, 200 rpm, 1 h
Plate 50–200 μL on LB+antibiotic (use 100 μL for ligations) 50–200 μL on LB+antibiotic

3.2 Efficiency Calculation

[ \text{Efficiency (CFU/μg)} = \frac{\text{Colony count} \times \text{Dilution factor} \times 1000}{\text{ng DNA plated}} ]

Example: 200 colonies from 100 μL of a 1:10 dilution of 1 ng pUC19 transformation plated: - Total cells: 200 × 10 × (950 μL / 100 μL) = 19,000 CFU - Efficiency: 19,000 / 1 ng × 1000 = 1.9×10⁷ CFU/μg

3.3 Quality Control Specification

QC Parameter DH5α (C1100) DH5α-T1 (C1180) BL21(DE3) (C1300)
Minimum efficiency (pUC19) 1×10⁸ CFU/μg 1×10⁹ CFU/μg 1×10⁷ CFU/μg
Freeze-thaw stability ≤ 1 cycle ≤ 1 cycle ≤ 1 cycle
Viability at -80°C (12 months) ≥ 80% ≥ 80% ≥ 80%
Contamination (non-E. coli) None None None
Blue-white screening > 98% blue colonies with intact lacZ > 98% N/A
Expression induction (BL21) N/A N/A > 90% induced cultures show target protein

4. Blue-White Screening Procedure

4.1 Required Materials

Item Specification
LB agar plates Containing 100 μg/mL ampicillin (or other selection antibiotic)
IPTG 0.1 M stock; add 40 μL per plate (final 0.4 mM)
X-gal 20 mg/mL in DMF; add 40 μL per plate (final 80 μg/mL)
Spread on LB agar plates 15 min drying at 37°C before use

4.2 Interpretation

Colony Color Interpretation
Blue Vector re-ligated without insert (intact lacZ)
White Insert successfully cloned (disrupted lacZ)
Pale blue Small insert may not fully disrupt lacZ; sequence-confirm
Mixed blue/white sectors Colony derived from multiple cells; re-streak

5. Storage and Handling

Parameter Requirement
Storage temperature -80°C (constant)
Shipping Dry ice (≤ 48 h transit)
Freeze-thaw Do NOT re-freeze (single-use aliquots: 50–100 μL)
Thawing On ice only (5–10 min); never warm to RT
Handling Use cold pipette tips; work quickly on ice; minimize handling
Shelf life 12 months from manufacture (if stored continuously at -80°C)

6. Troubleshooting

Issue Cause Solution
Few or no transformants Cells thawed incorrectly Always thaw on ice; never warm to RT
Heat-shock temperature/timing wrong Calibrate water bath to exactly 42°C; do not exceed 45 s
DNA amount too high (> 50 ng) Use 1–10 ng per 50 μL cells (plasmid) or 5–10 μL ligation
Antibiotic concentration too high Verify working concentration (e.g., ampicillin 100 μg/mL, kanamycin 50 μg/mL)
SOC/LB too cold after heat shock Use pre-warmed SOC (37°C)
Ligase salts inhibit transformation Purify ligation (ethanol precipitation or column clean-up) before transforming
Too many blue colonies (white screening) Incomplete X-gal/IPTG spread Spread fresh; use foil-wrapped X-gal (light-sensitive)
Vector lacZ intact (re-ligation) CIP-treat vector after linearization; use gel-purified vector
All white colonies (no blue control) No IPTG/X-gal added Always include pUC19 + X-gal/IPTG positive control
lacZΔM15 strain mixed up Verify strain genotype
Cells clump or precipitate Improper thawing Discard and use fresh aliquot
Multiple freeze-thaw cycles Aliquot at first use; never re-freeze
Low transformation with ligation Insert-to-vector ratio wrong Use 3:1 molar ratio (sticky) or 5:1 (blunt)
Insert contains secondary structures Linearize insert; use gel-purified DNA

▶ Related Protocol: Competent Cell Transformation Protocol ▶ See also: Cloning & Ligation Reagents

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