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Oligonucleotide-Antibody Conjugation Service

Custom antibody-oligo conjugates for immunoassays, single-cell and spatial biology, proximity assays, DNA-barcoded antibodies and exploratory AOC delivery programs.

45+ Years of Expertise ISO 9001:2015 / ISO13485:2016 Antibody → Single-Duplex Oligo Fit-for-purpose Q.C U.S.A Facilities - Texas
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Overview Formats Chemistry Selection Guide Engagement QC Applications Quality Related Services FAQ Reading Contact
Overview

Build Antibody-Oligo Conjugates Around Chemistry, Orientation and Analytics

Bio-Synthesis supports end-to-end oligonucleotide-antibody conjugation for research, diagnostic and translational workflows. We help engineer the oligo handle, linker, antibody preparation route, conjugation chemistry, purification method and release testing package.

Capabilities include maleimide-thiol, NHS-amine, SPAAC azide-DBCO, IEDDA TCO-tetrazine, oxime/hydrazone, Fc-glycan remodeling, Sortase A, transglutaminase, engineered cysteine and disulfide re-bridging strategies.

Our team supports antibody-oligo programs from feasibility through scale-up, including antibody buffer exchange, oligo synthesis, barcode design, conjugation cleanup, SEC-HPLC, SDS-PAGE/CE-SDS, A260/A280 OAR estimation, LC-MS oligo identity, packaging and documentation.

Antibody-Oligo Conjugation Workflow
Oligonucleotide strands moving toward antibody attachment sites Oligo barcode Click / linker Purified AOC
Conjugate Formats

Antibody and Oligonucleotide Formats We Support

Use this interactive selector to review antibody formats and oligonucleotide payloads without repeating two separate card-heavy sections.

Antibody Formats at a Glance

Bio-Synthesis can support common antibody formats for antibody-oligonucleotide conjugation, including full-length antibodies, fragments and engineered constructs.

IgG
monoclonal & polyclonal
Fragments
Fab, F(ab′)2, scFv
VHH
nanobody formats
Engineered
cysteine, glycan, tags
Monoclonal IgG
Human, mouse, rabbit and isotype-control IgG formats with lysine, cysteine or glycan-directed routes.
Polyclonal IgG
Antibody-oligo conjugation for assay development, detection workflows and custom reagent preparation.
Fragments
Fab, F(ab′)2 and scFv constructs for reduced steric burden, proximity assays and barcode applications.
Nanobody / VHH
Compact single-domain antibody formats compatible with click, IEDDA and site-directed workflows.
Engineered Antibodies
Engineered cysteine, glyco-engineered clones, Fc-fusions and site-specific antibody formats.
Panel & Kit Formats
Multiple antibodies, normalized concentration, vial or plate formatting, labels and documentation.

Oligonucleotide Payloads at a Glance

Oligo selection depends on the assay, barcode architecture, payload type, handle position, linker and final QC requirements.

DNA
barcode, PLA, immuno-PCR
RNAi
siRNA duplexes
ASO
gapmers & inhibitors
Custom
aptamer, branched, modified
Format Typical Applications Design Focus
DNA Barcodes CITE-seq, Ab-seq, immuno-PCR, PLA, spatial biology Barcode length, UMI, spacer and terminal handle
RNA Oligos Reporter RNA, structured RNA and exploratory RNA conjugates RNase-free handling, folding and stability
siRNA Duplexes Exploratory antibody-guided RNAi delivery Guide/passenger orientation, linker placement and duplex integrity
ASO / Gapmers Antisense research and antibody-guided oligo payload studies Backbone chemistry, terminal attachment and release strategy
miRNA Inhibitors Antagomirs, miRNA inhibitors and modulation studies Modified bases, stability and conjugation position
Aptamers Targeting, recognition and hybrid binding systems Preserve folding and binding after conjugation
Specialty Constructs Branched, dual-function, fluorophore or custom modified oligos Custom purity, identity and conjugate confirmation

Supported handles: amine • thiol • azide • DBCO • alkyne • tetrazine • TCO • biotin • PEG/TEG spacers • custom linkers.

Chemistry Platform

Choose the Right Antibody-Oligo Conjugation Route

Use the tabs to compare broad labeling, site-specific strategies, cleavable linkers and QC-centered route planning.

Broad Labeling at a Glance

Best for
Assay barcoding
Common use
IgG • DNA barcode
Design focus
Handle + spacer
QC focus
SEC + OAR
Modification Structure / Class Mechanism & Notes Stability Impact Typical Use
2′-O-Methyl (2′-OMe) 2′-O substitution Reduces RNase access; maintains A-form geometry and improves duplex stability. Moderate nuclease resistance; increased Tm. ASO wings, probes, siRNA, aptamers
2′-Fluoro (2′-F) 2′-F substitution Electronegative fluorine biases C3′-endo sugar pucker; tightens duplex and reduces RNase susceptibility. High resistance; increased Tm. siRNA, ASO, aptamers
2′-MOE 2′-O-methoxyethyl Bulky ethoxy group blocks nucleases; widely used in ASO gapmer wing designs. Strong resistance; increased Tm. ASO gapmer wings, steric-blocking ASO
LNA / BNA / cEt Bridged / constrained sugar Preorganizes sugar geometry for very strong binding and exonuclease resistance. Very high resistance; large Tm increase. ASO, probes, short high-affinity oligos
ENA / AmNA bridge Alternative bridged sugars Balance affinity, toxicity and stability for newer antisense designs. High resistance; increased Tm. ASO and RNA-targeting designs
UNA Unlocked acyclic sugar Increases flexibility; can reduce Tm and tune local structure. Context-dependent resistance; lower binding. Structure tuning, siRNA fine-tuning
GNA / TNA / HNA XNA artificial sugars Artificial sugar frameworks resist biological enzymes and enable specialized duplexing. Excellent resistance; variable Tm. Diagnostics and specialty research

Site-Specific Routes at a Glance

Best for
Orientation control
Common use
therapeutic R&D
Design focus
antigen binding
QC focus
homogeneity
Route Conjugation Site Primary Advantage Best Fit Notes
Fc-Glycan Remodeling Fc glycan region Orientation-preserving conjugation Antigen-binding preservation Strong option when Fab binding should remain unobstructed.
Sortase A LPXTG motif Defined enzymatic ligation Engineered antibodies and fragments Requires compatible engineered motif.
Transglutaminase Q-tag / glutamine sites Site-selective enzymatic coupling Homogeneous AOC development Route depends on accessible engineered site.
Engineered Cysteine Defined cysteine site Controlled thiol-directed coupling Site-specific AOC payloads Requires compatible engineered antibody and reduction control.
Disulfide Re-Bridging Reduced disulfide region Re-stabilized antibody linkage Controlled loading with antibody integrity focus Useful where hinge chemistry and stability are critical.

Linkers & Release at a Glance

Best for
spacing + release
Common use
AOC payloads
Design focus
sterics + trigger
QC focus
linker stability
Linker Function Common Application Design Note Code
PEG / TEG Spacer and solubility support Barcode, PLA, CITE-seq, AOC delivery Reduces steric interference near antibody surface. [PEG]/[TEG]
Disulfide Redox-sensitive release Exploratory oligo payload release Useful when cytosolic release is part of design. [SS]
Hydrazone / Oxime Aldehyde-directed or pH-sensitive linkage Glycan-directed or release-focused designs Requires route-specific stability review. [Hyd]
Val-Cit-PAB Enzyme-sensitive release Payload-style AOC design Useful for cathepsin-cleavable systems. [VC-PAB]

QC-Led Route Planning at a Glance

Best for
release confidence
Common use
translational lots
Design focus
OAR + aggregate
QC focus
orthogonal methods
Assay Purpose Why It Matters Typical Output
SEC-HPLC Monomer, aggregate and cleanup profile Confirms conjugation quality and aggregate control. Chromatogram, monomer % and aggregate %.
SDS-PAGE / CE-SDS Intactness and heavy/light-chain profile Supports reducing and non-reducing AOC review. Gel or electropherogram.
A260/A280 Oligo-antibody ratio estimation Estimates loading and helps compare lots. OAR estimate and concentration.
LC-MS Oligo Oligonucleotide identity Confirms oligo component before or after workflow as appropriate. Mass identity report.
Chemistry Selection Guide

Match the Conjugation Route to the Program Goal

Antibody-oligonucleotide conjugation can be achieved through multiple chemical and enzymatic routes. Selection depends on the antibody format, oligonucleotide payload, desired oligo-to-antibody ratio (OAR), conjugation site and downstream application.

Route Selection Logic

Start with the antibody format and available oligo handle, then select a chemistry that fits the desired OAR, binding sensitivity, purification strategy and downstream assay or delivery application.

Fast feasibility Bioorthogonal click Site-specific Cleavable linker Barcode panel
01

Fast Feasibility

NHS-Amine or Maleimide-Thiol

Best when speed and initial conjugation feasibility matter more than full homogeneity.

02

Bioorthogonal Coupling

SPAAC or IEDDA

Useful when clean, orthogonal reactive pairs are preferred for antibody-oligo ligation.

03

Binding Preservation

Fc-Glycan Remodeling

SKeeps conjugation away from Fab binding regions when antigen recognition is sensitive.

04

Controlled OAR

Sortase A, TGase, or Engineered Cysteine

Better for defined attachment sites, controlled loading and development-stage programs.

05

Payload Release

Cleavable Linkers

Use for exploratory AOC payloads where intracellular or triggered release is part of the design.

06

Barcode Panels

DNA Barcode Workflow

Recommended for CITE-seq, Ab-seq, PLA, immuno-PCR and multiplex antibody panel builds.

Final selection depends on: antibody source and buffer, available modification sites, oligo handle, desired OAR, linker length, purification method, aggregation risk, binding assay and release documentation.

Engagement Models

Flexible AOC Engagement Models

Choose the right level of support based on whether you need early feasibility, site-specific development, or production-ready antibody-oligo conjugates.

01

Discovery & Feasibility

Small-scale conjugation to evaluate antibody compatibility, oligo handle, linker performance, loading range, cleanup strategy and early analytical feasibility.

  • Proof-of-concept conjugation
  • Handle and linker screening
  • Preliminary SEC/OAR review
02

Development & Optimization

Advanced development support for site-specific conjugation, glycan remodeling, enzymatic routes, controlled OAR and enhanced analytical characterization.

  • Site-specific route development
  • OAR and aggregation optimization
  • Expanded QC packages
03

Production, Panels & Kitting

RUO production, DNA-barcoded antibody panels, normalized formats, custom packaging, labels, plates and project-specific documentation.

  • RUO conjugate lots
  • Barcode panels and assay kits
  • Packaging and documentation
Production Workflow

Integrated Workflow for Antibody-Oligo Conjugates

AOC production should feel like a controlled forward process: design input, antibody preparation, oligo build, conjugation, purification and release. The moving line below now belongs here because it visually represents the production path.

01
Scope & Design

Define antibody format, oligo payload, handle, linker, OAR target and application.

02
Antibody Prep

Buffer exchange, reduction, glycan remodeling or enzyme-compatible preparation.

03
Oligo Build

Synthesize DNA/RNA barcode, siRNA, ASO, aptamer or functionalized oligo handle.

04
Conjugation

Perform maleimide, NHS, click, IEDDA, glycan or enzymatic coupling.

05
Purification

SEC-HPLC, desalting, Protein A/G capture or route-specific cleanup.

06
QC & Package

Release with OAR, purity, identity, documentation, labels and packaging.

Analytical QC & Release

Orthogonal QC Package for AOC Release

Bio-Synthesis supports analytical characterization strategies for antibody-oligonucleotide conjugates using orthogonal methods that evaluate antibody quality, oligonucleotide identity, conjugation performance, purity and release-critical attributes.

Release Control Matrix

Use orthogonal assays to evaluate the antibody, oligonucleotide and final conjugate from different analytical angles.

SEC-HPLC

Monomer, aggregate, free antibody and conjugate cleanup profile.

CE-SDS / SDS-PAGE

Reducing and non-reducing heavy/light-chain profile and conjugate integrity.

A260/A280 OAR

Oligo-antibody ratio estimate, concentration and lot comparison.

LC-MS Oligo

Oligonucleotide mass identity confirmation and sequence-specific support.

Optional Binding

ELISA or application-specific binding check after conjugation.

Safety / Cleanliness

Endotoxin, bioburden, residual reagent or process impurity testing when needed.

Stability

Defined storage, freeze-thaw or application-specific stability studies.

Antibody Integrity
Oligo Identity
Conjugate Ratio
Aggregate Profile
Release Documentation
Applications

Application-Centered AOC Design

The right AOC design depends on whether the antibody is used as a detection reagent, proximity probe, barcode carrier or exploratory delivery vehicle.

PCR

Immuno-PCR / Digital ELISA

DNA-barcoded antibodies for amplified readout, low-abundance detection and ultra-sensitive assay development.

PLA

Proximity Ligation Assay

Paired antibody-oligo probes with complementary sequences for proximity-dependent ligation.

SC

CITE-seq / Ab-seq

Antibody barcode conjugates for single-cell proteogenomics, sample tags and UMI-containing workflows.

Tx

Exploratory AOC Delivery

Antibody-guided ASO, siRNA or oligo payload designs with cleavable or spacing linkers.

Quality Systems

Quality Support for Antibody-Oligo Programs

Delivery, diagnostic and translational AOC programs require traceable materials, defined process conditions, orthogonal analytics and documentation.

QMS

ISO-Supported AOC Manufacturing Platform

Bio-Synthesis supports custom antibody-oligonucleotide conjugation, purification, analytical characterization and documentation across feasibility, assay-development and translational workflows.

ISO 9001:2015 Quality management system
ISO 13485:2016 Medical-device quality framework
Full Analytics SEC-HPLC, CE-SDS, OAR, LC-MS
Scale-Up Support Feasibility through production lots

FAQ

Which antibody and oligo formats can Bio-Synthesis conjugate?
Bio-Synthesis supports monoclonal IgG, antibody fragments, VHH/nanobody formats, engineered antibodies and polyclonal IgG with DNA barcodes, RNA oligos, siRNA, ASO, antagomir, aptamer and functionalized oligonucleotides depending on handle, linker and QC requirements.
How should I choose a conjugation chemistry?
Use NHS-amine for broad lysine labeling, maleimide-thiol for cysteine-directed workflows, SPAAC for copper-free click chemistry, IEDDA for fast orthogonal ligation and glycan or enzymatic routes when orientation and homogeneity are priorities.
Can you support site-specific AOC conjugation?
Yes. Options can include Fc-glycan remodeling, Sortase A, transglutaminase, engineered cysteine and disulfide re-bridging routes, depending on the antibody format and project goals.
What QC is recommended for AOC release?
Typical QC includes SEC-HPLC, SDS-PAGE or CE-SDS, A260/A280 OAR estimation, LC-MS for the oligo component and optional binding ELISA, endotoxin, bioburden, residuals and stability testing.
Can you make DNA-barcoded antibodies for single-cell or spatial workflows?
Yes. Bio-Synthesis can support oligo barcode synthesis, handle selection, antibody conjugation, cleanup, normalization, labeling and packaging for DNA-barcoded antibody workflows.
What information is needed for a quote?
 Provide antibody format and amount, oligo sequence and handle, desired chemistry, target OAR, application, purification preference, QC requirements, buffer constraints, scale and packaging format.
More FAQ'sAll FAQ's
Before Requesting a Quote

Information Helpful for an AOC Quote

Antibody IgG, Fab, VHH, clone, amount
Oligo Sequence, length, handle
Chemistry NHS, maleimide, click, glycan
OAR Target loading or range
QC SEC, CE-SDS, OAR, LC-MS
Format Tube, vial, plate, barcode
Contact & Quote Request

Need help designing or manufacturing an antibody-oligo conjugate?

Share your antibody format, oligo sequence, handle, linker preference, conjugation route, target OAR, application, purification, QC and packaging requirements. Bio-Synthesis can help evaluate the conjugation route and build a practical AOC workflow around your program.
Request a Quote Speak to a Scientist

Need help before quoting?

Email: info@biosyn.com
Phone: 800-227-0627 (US/CAN)
Phone: +001-972-420-8505 (INT)
AOC

Route Selection

Choose broad labeling, site-specific chemistry, glycan-directed conjugation or cleavable linker design.

NHS Maleimide SPAAC IEDDA
QC

Release Package

SEC-HPLC, SDS-PAGE/CE-SDS, A260/A280 OAR, LC-MS, optional binding and safety assays.

SEC CE-SDS OAR LC-MS
Recommended Reading

Recommended Reading & Literature References

Use this section to support scientific credibility while keeping the page focused on AOC design, conjugation chemistry and analytical release.

  1. Fredriksson S, et al. Protein detection using proximity-dependent DNA ligation assays. Nature Biotechnology. 2002.
  2. Sano T, Smith CL, Cantor CR. Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates. Science. 1992.
  3. Stoeckius M, et al. Simultaneous epitope and transcriptome measurement in single cells. Nature Methods. 2017.
  4. Peterson VM, et al. Multiplexed quantification of proteins and transcripts in single cells. Nature Biotechnology. 2017.
  5. Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angewandte Chemie International Edition. 2001.
  6. Blackman ML, Royzen M, Fox JM. Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity. Journal of the American Chemical Society. 2008.
  7. Agarwal P, Bertozzi CR. Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development. Bioconjugate Chemistry. 2015.

Suggested page note: Literature references are provided for scientific background. Final AOC design should be evaluated within the antibody format, oligonucleotide handle, conjugation route, linker, OAR target, purification method and analytical release plan.

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 45+ years of delivering high quality, fast and scalable synthetic biology solutions.

Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

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