Catch sticky candidates before PK fails.
Off-target plasma binding sinks bioavailability and drives fast clearance, and it rarely surfaces before the first in vivo PK study. MACS® Matchmaker profiles your candidate panel directly in undiluted human plasma, with full kinetics and within-chip replicates from a single chip in approximately one hour.
Up to 64 Candidates per chip | ~1 hour Plasma SCK run | 100% Undiluted human plasma | DDI Pre-conjugated panel |
Plasma stickiness is the late-stage failure mode that current discovery screens miss.
Why plasma binding drives clinical attritionOff-target plasma binding sequesters dose, accelerates clearance, and inflates required dosing. Serum proteins outnumber the drug target by orders of magnitude in human plasma. Even sub-micromolar affinity for abundant carriers (HSA, α1-acid glycoprotein, immunoglobulins, lipoproteins) therefore measurably reduces the free fraction. The differences that decide PK success are sub-twofold and invisible to screens that only bin candidates as pass or fail. Once a sticky lead enters lead optimization, catching it later is expensive: in pharmacokinetic (PK) studies, in toxicology, in early clinical. The cost can be measured in months and millions. The right place to triage plasma stickiness is at hit-to-lead, before the candidate is committed. | Current methods can't see it in timeEquilibrium dialysis takes 4 to 18 hours per sample and gives only equilibrium fraction unbound, no kinetics. SPR and BLI require plasma dilution or depletion to manage non-specific binding. That introduces matrix artifacts and removes the physiological conditions the assay is meant to read. LC-MS readout still demands sample prep and is blind to the off-target carrier identity. MACS® Matchmaker reads coherent mass density directly. Specific binding stays clean in undiluted human plasma because the chip rejects matrix noise intrinsically. Full kinetics, kon and koff, in approximately one hour, on the same instrument and the same workflow you already use for affinity and effector function. |
Plasma binding belongs IN your discovery cycle, not after IND.
Stickiness to plasma has to be screened during candidate selection, not after. Conventional methods are too slow, demand too much material, or rely on plasma dilution that introduces matrix artifacts. Plasma binding is therefore typically measured only on a short-list, late, when course corrections are expensive. The Plasma Protein Binding Panel uses the same focal molography surface as the target-binding assay. The candidates are immobilized via DNA-directed immobilization (DDI) with a single conjugation chemistry, and the protocol is the same single-cycle kinetics. The panel drops into the same pipeline, the same buffer, the same sample volume, the same instrument.
⏱ Off-instrument dialysis to 1-hour on-instrument SCK Equilibrium dialysis is the textbook reference but takes 4 to 18 hours per sample and gives only equilibrium fraction unbound, no kinetics. MACS® Matchmaker runs the plasma binding panel as a single SCK run on the same chip you use for target binding. It takes approximately one hour per candidate. | ⤆ Plasma dilution to undiluted human plasma SPR and BLI cannot measure binding in undiluted plasma because matrix non-specific binding overwhelms the signal. MACS® Matchmaker reads coherent mass density directly. Specific binding stays clean even at 100% plasma, so the binding constants reflect physiological conditions. |
≈ Single-pair throughput to 64 in parallel Dialysis processes one sample per well, hours apart. SPR cycles through a small handful per run. MACS® Matchmaker resolves up to 64 candidate-plasma interactions in parallel on a single chip, with within-chip replicates for confidence intervals from a single experiment. | ⚙ Late-stage triage to every discovery cycle Off-instrument plasma binding gets measured only on a triaged short-list, after affinity ranking. MACS® Matchmaker lets the plasma panel run on every candidate at every cycle, alongside affinity and effector function. PK liabilities surface at the earliest decision point. |
Where the Plasma Protein Binding Panel delivers value.
The same chip, sample, and protocol address three distinct workflows across antibody discovery and developability.
Discovery Drop sticky candidates before lead optimization Run the panel on every candidate alongside the target affinity measurement. Surface plasma stickiness at the earliest selection point, before resources are committed to lead optimization. The plasma binding readout pairs directly with KD in candidate-ranking tables, scoring each candidate on the developability triad: high KD, low Rmax, fast koff. | Lead Optimization Rank engineered variants on the PK axis Fc engineering, charge-patch removal, and CDR optimization each shift the plasma interaction profile in unintended directions. The panel ranks engineered variants on the plasma binding axis with the same within-chip statistics as the affinity measurement, in the same experiment. | Developability Score every candidate before lead-nomination Build the plasma binding profile into the standard developability data package alongside FcRn, target KD, polyreactivity, and hydrophobic interaction chromatography. The panel returns a calibrated PK-risk score that travels with the candidate into formulation and IND-enabling work. |
One workflow. Two candidate classes.
Biologics Plasma Binding, up to 8-plexThe primary configuration for antibody developability. Candidates (antibodies, VHHs, bispecifics, fusion proteins) are DDI-immobilized on the chip; undiluted human plasma flows over them as the analyte. The readout is the bulk serum-interaction KD, koff, and Rmax per candidate, ranked by the developability triad of high KD, low Rmax, fast koff. Built for the antibody developability workflow at every discovery cycle. Drop sticky leads early without committing material or time to off-instrument PK studies. | Small Molecule Plasma Binding, up to 16-plexThe carrier-protein configuration for medicinal chemistry. Human serum albumin, α1-acid glycoprotein, lipoproteins, and additional plasma carriers are DDI-immobilized as ligands; the drug candidate flows over them as the analyte. The readout is per-protein KD, kinetics, and fraction unbound from the dose-response fit. Down to ~350 Da analyte molecular weight. Built for DMPK and medicinal chemistry workflows. Switch between the biologics and small molecule configurations on the same instrument with the same workflow. |
One injection series. Full kinetics. Approximately one hour.
The chip is loaded once with the pre-conjugated panel via DNA-directed immobilization. Each candidate then runs a single 9-point plasma dilution series (0.39% to 100% undiluted human plasma). The binding response is read simultaneously across all candidates on the chip. Between samples, low-affinity plasma interactions clear with a running buffer wash; higher-affinity binders are removed with a dedicated regeneration step. Either way the candidate chip is reused across the sample series, including successive plasma types for cross-species PK bridging.
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Up to 64 candidates. One hour. One chip.
Run the Plasma Protein Binding Panel on a real candidate. Your candidate. Book a 30-minute discovery call with one of our application scientists.
What makes MACS® Matchmaker the purpose-built solution for this workflow.
Up to 64 Multiplexed candidates per chip Profile a full antibody panel or carrier-protein set on one chip. Within-chip replicates per ligand return mean and confidence interval from a single run, no separate plates and no batched runs. | KD + kinetics Full kinetics, not just equilibrium MACS® Matchmaker returns equilibrium KD plus association and dissociation rates from a single plasma SCK. Fast koff separates reversible binding from sequestration. Dialysis returns only equilibrium fraction unbound and cannot make that call. | Single chemistry Plug-and-play panel Carrier proteins (HSA, α1-AGP, lipoproteins) and Oligo Adapters (Strep-Tactin XT, NeutrAvidin, trisNTA) are pre-conjugated and ready-to-use. DDI loading takes one injection, lot-to-lot reproducibility is designed in. |
~1 hour Same chip as target binding The plasma binding panel runs on the same MACS® Matchmaker chip and the same sample injection used for the target affinity assay. PK liability moves into the discovery cycle instead of running parallel to it. | pg/mm² Direct mass detection Coherent mass density at each ligand spot is a direct physical readout of bound mass, not a refractive-index proxy. KD, koff, and Rmax are therefore quantitative numbers rather than relative semi-quantitative scores. | Built-in QC Reference + replicates Per-chip Oligo reference and non-binding negative control spots deliver per-injection quality control: absence of signal flags candidate or run failure before any KD is computed. Within-chip replicates per ligand provide confidence intervals from a single experiment. |
MACS® Matchmaker vs. plate-based plasma binding methods.
Equilibrium dialysis and dilution-based SPR/BLI are the established plasma-binding methods. The comparison below addresses the developability-screening workflow specifically.
| Parameter | MACS® Matchmaker | Dialysis / SPR / LC-MS |
|---|---|---|
| Time per candidate | ✓ ~1 hour single chip | 4 to 18 hours per dialysis |
| Sample consumption | ✓ μg-scale, shared with target assay | mg-scale per dialysis or SPR run |
| Same workflow as target binding | ✓ Yes, same chip, same sample | No, separate instrument and matrix prep |
| Plasma matrix | ✓ Undiluted human plasma | Diluted, depleted, or buffer-substituted |
| Kinetics resolved | ✓ Full kon, koff, Rmax in one run | None (dialysis), yes (SPR but diluted), none (LC-MS) |
| Replicates per ligand | ✓ Up to 8 within-chip replicates per ligand, or up to 64 candidates at single-mologram density | Single well per condition (dialysis); reference subtraction (SPR) |
| Quantitative score | ✓ KD, koff, Rmax per candidate | Fraction unbound only (dialysis); no carrier identity (LC-MS) |
The full panel composition and benchmark dataset is coming soon.
An Application Note is in preparation. It covers the two-configuration panel design (biologics plasma binding + small-molecule carrier panel), the per-ligand rationale, and the recommended controls. It also includes a public-reference validation dataset of FDA-approved antibodies profiled in undiluted human plasma. Drop us a note to be notified the moment it goes live.