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Hybridoma Monoclonal Antibody Development

Bio-Synthesis's success rate in Custom Hybridoma Development for Monoclonal Antibodies from fused cell line is greater than 95%. Relying on our proprietary Antigen Identifier design tool, flexible peptide synthesis platform and proprietary SP-Max™ adjuvant, we deliver high quality monoclonal antibodies in a short turn-around time at affordable cost.

 
Hybridoma Monoclonal Antibodies
 
Hybridoma Monoclonal Antibodies

Each of our monoclonal antibody development packages include:

  • Immunization of antigen into 5 BALB/c mice
  • Screening of test bleeds against immunizing antigen to isolate a mouse with the highest IgG titer
  • Fusion of one mouse's spleen to the FO myeloma cells
  • Screening of positive wells following fusion for IgG specific clones using immunizing antigen
  • Two sub-cloning steps to ensure a complete monoclonal colony
  • Cell line stabilization of up to 3 cell lines
  • Isotype report on each final clone provided, confirming Ig class
  • Cell line banking of backup vials for 1 year following final clone shipment

Quality Control

The following quality control measurements are employed to create the highest quality monoclonal antibodies commercially available:

  • ELISA against the antigen
  • SDS/PAGE
  • Immunocytochemistry(ICC)
  • HPLC
  • Western Blot

Guarantees

  • Standard Protein mAb (mAb1000) or Standard Peptide mAb (mAb3000) packages: 3 ELISA positive clones
  • Premium Protein mAb Package (mAb2000): up to 3 positive clones for BSI screening method selected (WB or ICC)
  • Premium Peptide mAb Package(mAb4000): 3 ELISA positive clones; no guarantee for WB or ICC reactivity; see Terms and Conditions for more details
  • Client-Provided Peptide Antigens: no guarantee provided.

Protein vs. Peptide Antigens

There has been much discussion about using recombinant or fusion proteins versus peptides as antigens. IgG antibodies work for a wide variety of applications, such as western blot, immunostaining, immunoprecipitation, and more. When obtaining IgG antibodies, a protein antigen works better for custom monoclonal antibody development. The immune system of a mouse responds better to proteins due to the higher number of linear and conformational epitopes. Ultimately, the more diverse of an immune system response usually results in antibodies against multiple locations on the protein. Each of these protein locations has unique properties.

Peptide antigens are usually only linear in nature and also have fewer epitopes. To increase the total number of epitopes available for the mouse immune system to respond to, it is recommended to use peptides of 20-30 residues in length. Increasing the immune response will increase the likelihood of success of your custom monoclonal antibody project. Going with shorter peptide sequences of less than 20 residues in length usually only works for ELISA.

Fusion Partners (protein antigens)

When submitting a protein antigen for monoclonal development, it is highly recommended to cleave all GST tags or other large fusion partners from the protein. Usually, large fusion partners are highly immunogenic. If they are not removed before immunization, a dual ELISA screening process must be performed to ensure positive responses are results of protein and not to the fusion partner. For this process, high ELISA titers are screened against the protein, while low ELISA titers are screened against the fusion partner.

Custom Monoclonal Antibody Development Antigen Requirements:

  • Purity: As pure as possible. A purity of >90% is highly recommended
  • Solubility: The antigens need to be soluble for screening purposes.
  • Types: We can work with peptides, proteins, and enzymes. .
  • Quantities: Around 5 mg of the antigen is needed. Immunization uses 1 mg, while the last 4 mgs are used for screening. The minimum amount needed to start a project is 0.5 mgs if additional amounts will be supplied throughout the project.
  • Conjugation:Smaller antigens that have a molecular weight of 10kDa or less will need to be conjugated to a large carrier protein. This ensures that the conjugate is large enough in size in order to illicit a strong immune response. We would need either 1 mg of the conjugate provided by the researcher or 2-3 mgs of the material to perform the conjugation.

Monoclonal Antibody Related Services

Go-Monoclonal Antibodies

Bio-synthesis provides a broad range of high-quality ready to go polyclonal and monoclonal antibodies in the area of: Apoptosis & Cancer; Neuroscience; Cell Structure; Epigenetics & Nuclear Function; Epitope Tags & General Use; Infectious Diseases; Inflammation & Immunology; Cell Signaling; Stem Cell Research; Protein Trafficking Secondary Antibodies; and Metabolism. See details

Ascites Production

This is done by injecting the hybridoma cell line into the primed peritoneal cavity of BALB/c mice and harvesting the resulting fluid that contains antibodies secreted by the hybridoma. See details

In vitro Production

Monoclonal antibody production by in-vitro cell culture. Serum and serum-free medium formulation are available upon request. See details

Monoclonal Antibody Purification

Bio-Synthesis can purify your monoclonal antibodies utilizing a wide array of protein purification methods; from research (mg) to scale-up (grams) quantity. See details

Monoclonal Antibody Labeling

Broad range of fluorescent or nonfluorescent labels can be conjugate to monoclonal antibody produce at Bio-Synthesis or supplied by customers. See details

Monoclonal Antibody Bioconjugation

Bio-synthesis can conjugate your monoclonal antibody with oligonucleotide, fluorescent labels, enzymes, solid surfaces, visit our monoclonal bioconjugation services See details

Endotoxin Testing and Removal Services

Take advantage of our low cost and expertise in endotoxin removal services for your antibodies, proteins, and nucleic acids. See details

Peptide Hybridoma Monoclonal Antibody Development

Bio-Synthesis offers a variety of Hybridoma Development Monoclonal Antibody Production Services. Customer personalized packages are also available. To initiate a custom contract monoclonal antibody service project, please contact our Technical Service Department at: (800) 227.0627 or contact us online. A project manager will be assigned to help you select or design the best service for your specific needs.

Standard Peptide Monoclonal Antibody Packages: Cat No. mAb3000

Hybridoma Monoclonal Antibody Development Cycles Deliverable
Phase I Antigen Processing (1-2 weeks)
Synthesis: up to 25 aa peptide >90% pure 5 mgs of unconjugated peptides
Conjugation: KLH with 5-10 mg of peptide via cysteine Mass spec and HPLC reports
Phase II Immunization and Screening of Antibody Titer (10-16 weeks)
Immunization: 5 Balb/c mice using standard immunization protocols ELISA evaluation of titer
Screening: Tail bleed IgG Ab titer by ELISA  
Phase III Fusion, Plating and Screening (2-3 weeks)
Fusion: Fusion on best mice, potential parental clones will be expanded into 24-well plates ready to harvest relatively large amount of tissue culture supernatant for further antibody screening by ELISA. ~1 ml of culture supernatant
Screening: ELISA assay on fused cell clone ELISA evaluation of titer
Feedback from customer is required within 1 week to ensure viability of clones
Phase IV Subcloning, Expansion and Stabilization (4-6 weeks)
Subcloning: Two rounds of sub-cloning steps from parental clone to ensure full monoclonal colony ~1 ml of culture supernatant
Screening: The hybridoma cells are screened by ELISA during each subcloning step. ELISA evaluation of titer
Stabilization and Expansion: Up to 3 positive cells are stabilized and expanded in T25 flask. Two vials of cell culture
Cryopreservation: Cell line banking of backup vials for 1 year. Cryopreserve hybridoma cell up to 1 year
Isotyping: Isotyped on final clone to confirm lg class Isotyping report
Feedback from customer is required within 1 week to ensure viability of clones

Premium Peptide Monoclonal Antibody Packages: Cat No. mAb4000

Hybridoma Monoclonal Antibody Development Cycles Deliverable
Phase I Antigen Processing (1-2 weeks)
Synthesis: up to 25 aa peptide >90% pure 5 mgs of unconjugated peptides
Conjugation: KLH with 5-10 mg of peptide via cysteine Mass spec and HPLC reports
Phase II Immunization and Screening of Antibody Titer (10-16 weeks)
Immunization: 5 Balb/c mice using standard immunization protocols ELISA evaluation of titer
Screening: Tail bleed IgG Ab titer by ELISA  
Phase III Fusion, Plating and Screening (2-3 weeks)
Fusion: Fusion on best mice, potential parental clones will be expanded into 24-well plates ready to harvest relatively large amount of tissue culture supernatant for further antibody screening by ELISA. ~1 ml of culture supernatant
Screening: ELISA assay on fused cell clone ELISA evaluation of titer
Feedback from customer is required within 1 week to ensure viability of clones
Phase IV Subcloning, Expansion and Stabilization (4-6 weeks)
Subcloning: Two rounds of sub-cloning steps from parental clone to ensure full monoclonal colony ~1 ml of culture supernatant
Screening: The hybridoma cells are screened by ELISA during each subcloning step. ELISA evaluation of titer
ELISA Assay and Western Blot with cell or tissue lysate or Immunochemistry (ICC) Western Blot (WB) or ICC reports
Stabilization and Expansion: Up to 3 positive cells are stabilized and expanded in T25 flask. Two vials of cell culture
Cryopreservation: Cell line banking of backup vials for 1 year. Cryopreserve hybridoma cell up to 1 year
Isotyping: Isotyped on final clone to confirm lg class Isotyping report
Feedback from customer is required within 1 week to ensure viability of clones

Protein Hybridoma Monoclonal Antibody Development

Available service for pre-immunization antigen processing and modification

  • Homogenization of antigen in Gels or nitrocellulose slices
  • Conjugation of antigen for immunization (KLH or other carrier)
  • Conjugation of antigen to BSA for screening hybridomas
Antigen requirements:
  • Protein: 5mgs soluble protein; 1mg for immunization and 4mgs for ELISA screening; recommend removing large fusion partners from protein
  • Peptide or small antigens: small antigens (with a molecular weight of <10kDa) are recommended to be conjugated to a carrier protein to initiate a strong immune response. Biosyn requires 3mgs conjugate, or 4mgs unconjugated peptide/small antigen for conjugation, and 4mgs unconjugated peptide/small antigen for ELISA screening, antigen purity of >90% recommended for hybridoma development

Standard Protein Monoclonal Antibody Packages: Cat No. mAb1000

Hybridoma Monoclonal Antibody Development Cycles Deliverable
Phase I Immunization and Screening of Antibody Titer (10-16 weeks)
Immunization: 5 Balb/c mice using standard immunization protocols ELISA evaluation of titer
Screening: Tail bleed IgG Ab titer by ELISA  
Phase II Fusion, Plating and Screening (2-3 weeks)
Fusion: Fusion on best mice, potential parental clones will be expanded into 24-well plates ready to harvest relatively large amount of tissue culture supernatant for further antibody screening by ELISA. ~1 ml of culture supernatant
Screening: ELISA assay on fused cell clone ELISA evaluation of titer
Feedback from customer is required within 1 week to ensure viability of clones
Phase III Subcloning, Expansion and Stabilization (4-6 weeks)
Subcloning: Two rounds of sub-cloning steps from parental clone to ensure full monoclonal colony ~2 ml of culture supernatant
Screening: The hybridoma cells are screened by ELISA during each subcloning step. ELISA evaluation of titer
Stabilization and Expansion: Up to 3 positive cells are stabilized and expanded in T25 flask. Two vials of cell culture
Cryopreservation: Cell line banking of backup vials for 1 year. Cryopreserve hybridoma cell up to 1 year

Premium Protein Monoclonal Antibody Packages: Cat No. mAb2000

Hybridoma Monoclonal Antibody Development Cycles Deliverable
Phase I Immunization and Screening of Antibody Titer (10-16 weeks)
Immunization: 5 Balb/c mice using standard immunization protocols ELISA evaluation of titer
Screening: Tail bleed IgG Ab titer by ELISA  
Phase II Fusion, Plating and Screening (2-3 weeks)
Fusion: Fusion on best mice, potential parental clones will be expanded into 24-well plates ready to harvest relatively large amount of tissue culture supernatant for further antibody screening by ELISA. ~1 ml of culture supernatant
Screening: ELISA assay on fused cell clone ELISA evaluation of titer
Feedback from customer is required within 1 week to ensure viability of clones
Phase III Subcloning, Expansion and Stabilization (4-6 weeks)
Subcloning: Two rounds of sub-cloning steps from parental clone to ensure full monoclonal colony ~2 ml of culture supernatant
Screening: The hybridoma cells are screened by ELISA during each subcloning step. ELISA evaluation of titer
ELISA Assay and Western Blot with cell or tissue lysate or Immunochemistry (ICC) Western Blot (WB) or ICC reports
Stabilization and Expansion: Up to 3 positive cells are stabilized and expanded in T25 flask. Two vials of cell culture
Cryopreservation: Cell line banking of backup vials for 1 year. Cryopreserve hybridoma cell up to 1 year
Isotyping: Isotyped on final clone to confirm lg class Isotyping report
Feedback from customer is required within 1 week to ensure viability of clones

Links and Resources

Useful Links

Hybridoma Development Terms and Conditions

Guarantees:

Standard Protein (mAb1000) or Standard Peptide mAb (mAb3000) packages : Bio-Synthesis, Inc. will guarantee up to three (3) ELISA positive hybridomas to the immunogen with 1 x 105 cells of each clone to either a protein antigen or a peptide antigen BSI selected and synthesized. Because of the nature of hybridomas, and antibodies in general, it is not possible to guarantee that the clones will work for applications other than ELISA, or that a clone will work for multiple applications.

Premium Protein mAb packages (mAb2000): Bio-Synthesis, Inc. will guarantee up to three (3) positive hybridomas for the screening application (western blot or immunocytochemistry) selected by the client with 1 x 105 cells of each clone.

Premium Peptide mAb packages (mAb4000): Bio-Synthesis, Inc. will guarantee up to three (3) ELISA positive hybridomas to the peptide antigen with 1 x 105 cells of each clone. Bio-Synthesis cannot guarantee reactivity for a specific application with peptide antigens; if the first fusion does not yield clones that are positive for the screening application chosen by the client (western blot or immunocytochemistry), a second fusion will be performed at no charge. Bio-Synthesis can terminate the project if the second fusion is not successful in yielding clones for the selected screening application and will not invoice phase III or will refund phase III if paid and client will only pay for peptide synthesis, conjugation, immunization, and one fusion.

Researcher Screening of Positive Wells: In order to improve the chances of obtaining antibodies suitable to your needs, clients have the option of screening the cultured supernatants from up to 100 positive wells following fusion. If this option is ordered, client results must be forwarded to Bio-Synthesis within 5 days of shipping of the supernatant samples. After this time a non-refundable per diem maintenance fee will be charged to your account. Because of the time critical nature of cloning, selections received after the 5day period will void any expressed or implied guarantees. Please note Bio-Synthesis cannot guarantee the continued reactivity seen in supernatants throughout sub-cloning.

Additional Information:

Antibodies that work well in one application may not work in another. We can, however, guarantee that each clone will recognize the immunogen in ELISA as this is our primary method of screening. The success of a project is dependent upon the immunogen, screening methods for hybridomas, etc. We highly recommend screening positive wells, especially if a peptide immunogen is used as this will increase the chances of developing a cell line that produces monoclonal antibodies that work in your target application. Additional positive clones may be available at additional cost.

We cannot guarantee the success of a project where the customer provides the antigen; however it is our experience that monoclonal projects using a recombinant protein yield monoclonal antibodies that have a higher recognition rate to the native protein than by using a peptide immunogen. The customer must also be aware that a customer-provided immunogen may not yield the immune response required for fusion. If the customer provides the immunogen there will not be a refund for phase one if there is insufficient titer for fusion following the 6th test-bleed in the immunization protocol.

If there is a successful fusion with no resulting ELISA-positive clones, phase one will not be refunded, although we will perform a second fusion at no charge. If the customer is not satisfied with the positive wells at screening or final clones they may opt to pay for another round of fusion and/or sub-cloning at additional cost.

Reference/Citing:

1.
K Terasawa et al. " Synthetic Pre-miRNA-Based shRNA as Potent RNAi Triggers." Journal of Nucleic Acids, Volume 2011 (2011), article ID131479
2.
B. Wang et al. "Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example." Virology Journal 2011, 8:405
3.
F. Yang et al. "Long non-coding RNA high expressed in hepatocellular carcinoma (lncRNA-HEIH) facilitates tumor growth through enhancer of zeste homolog 2. " Hepatology, 2011.
4.
C. Braconi et al. " MicroRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. " Oncogene. 2011, 1-7
Ordering Services
To place an order or request a quotation, please proceed to our custom Order/Quote page or Contact Us for any other questions.
Order can be placed with either a PO (Purchase Order) or credit card. You may place order online using our secure online ordering system. Our customer service representatives are available 24 hours a day, Monday through Friday, to assist you.
   
We accept POs and major credit cards ( ). Your credit card will be billed under "Bio-Synthesis, Inc." Please complete and return our Business Credit Application. For international orders, we must apply the full charge at the time of the order is placed. In the unlikely event that any given order cannot be filled, our guarantee will take the form of a full refund.