Newsletter #16

We are pleased to present the 16th edition of the Sapidyne Newsletter. In this issue, our Publication Spotlight examines pioneering research from A-Alpha Bio, highlighting their application of KinExA technology in measuring tight binders that are beyond the limit of detection for other technologies. The Future of Solid Phase addresses the transition from microplastic-based beads to glass beads, outlining the environmental and regulatory imperatives driving this shift. For researchers seeking actionable insights, the Solid Phase Selection Guide provides expert recommendations to identify the optimal solid phase for your experiments. Additionally, we invite you to explore Touring Idaho, where we share notable experiences from the Gem State, and introduce the beloved companions in Sapidyne Office Dogs, who bring joy to our workplace. Enjoy the read!

    Publication Spotlight

    AlphaBind, a Domain-Specific Model to Predict & Optimize Antibody-Antigen Binding Affinity

    A-Alpha Bio, Seattle, WA • Nvidia Corporation, Santa Clara, CA
    Aditya A. Agarwal, James Harrang, David Noble, Kerry L. McGowan, Adrian W. Lange, Emily Engelhart, Miranda C. Lahman, Jeffrey Adamo, Xin Yu, Oliver Serang, Kyle J. Minch, Kimberly Y. Wellman, David A. Younger, Randolph M. Lopez, Ryan O. Emerson

    In 2024, A-Alpha Bio released a study showing their use of KinExA to measure tight binders that were beyond the limit of detection for BLI.

    “Several AAB-PP489 candidates had binding affinities outside the accurate range of BLI and failed to generate a reliable off-rate (i.e., reported as < 1.0E-4/s).”

    The sensitivity of KinExA played an important role in characterizing candidates with superior binding affinity.

    “KinExA was used to confirm affinities for the top candidate from each optimization strategy…”

    The range of affinities measured by KinExA was 310 fM to 56.5 pM whereas the range of BLI measurements was from 211 pM to 54.5 nM.

    A-Alpha’s use of AlphaBind, an artificial intelligence (AI) model, helped determine the specific sequences responsible for producing the antibodies. The model uses protein language model embeddings and pre-training on large antibody-antigen binding data sets to optimize antibody affinity with high accuracy.

    FULL ARTICLE

      The Future of Solid Phase

      For years, Sapidyne has supported a plastic bead solid phase for use in adsorption coating. While they have worked well for a long time, they will no longer be available once our current stock has run out.

      Why switch from plastic? In a word – Microplastics. Microplastics are coming under increasing regulations and bans. New in 2025, sales of plastic beads will have to be accompanied by the EU statement:

      “The synthetic polymer microparticles supplied is subject to conditions laid down by entry 78 of Annex XVII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council”.

      The US, and especially California, are also working on tighter regulations and some bans. Because of the tightening regulations, sourcing plastic beads is getting more difficult and expensive. We have had to switch sources twice already, and when our current supply of Polystyrene beads are gone, we will be discontinuing plastic beads completely.

      The benefits of switching to glass beads include:

      • Not an environmental concern for our customers.
      • No concern of future supply chain difficulties or bans.
      • Easier to work with, both for us in manufacturing and for users when coating.

      Glass Adsorption beads are currently available for purchase in 10 pack aliquots ready for coating (440425), or in 25 gram quantities (440428). Ideal coating concentrations fall between 20-30 ug/ml. Increasing the coating concentration can lead to a stronger signal, but there will be diminishing returns so the signal boost achieved may not justify the additional material used.

      Glass Beads will only work with a KinExA 4000 instrument and will need to be used with Red Propellers (483816), a Bead Retriever (880350), Modified Wash Station (830580), and software version 4.7.6 or newer. If you do not have these parts or are unsure if you can use Glass Beads, please contact Sapidyne.

       

      Join Us

      Antibody Engineering & Therapeutics — December 14-17, 2025, San Diego. The #1 Antibody & Protein Conference: Your Path to Commercial Success.

      Solid Phase Selection Guide

      Selection of an optimal solid phase can increase measurement sensitivity and decrease background noise. Choosing which one will depend on the characteristics of the coating molecule that captures the constant partner in solution. Use the information below to decide what type of solid phase to try; There are a variety that can be used on the KinExA® instrument.

      See Table 1 for more information on common solid phases and their requirements.

      Solid Phase Considerations

      The size of the coating molecule is the first thing to consider for bead selection.

      • Large molecules (>~20 kDa) and small molecules conjugated to larger proteins, such as BSA, typically adsorption coat well to hard beads (e.g. Glass and Polystyrene).
      • Small, unconjugated, molecules (<~20 kDa) work best covalently coupled to soft beads (e.g. Azlactone and Sepharose).
      • Another consideration is if the molecule has been coupled to a plate or beads using another platform.
        • Often a molecule can be coupled to the appropriate solid phase using the same immobilization chemistry as an ELISA plate or SPR surface.
        • If pre-coated beads for an affinity column are at hand, they can be used for a KinExA experiment. Bead requirements can be read in the self-titled section on Page 5.

      If the coating material is expensive or limiting, try reversing the assay first. If it cannot be reversed, search for a biotinylated version of the molecule.

      • Biotinylated molecules can be coated onto “hard” beads that have first been coated with Streptavidin.
      • For more information on this coating procedure see How to Guide 208 Biotinylated Coating.

      In some cases, adsorption coating and/or covalent coupling through primary amines can mask the binding site of interest. In that case, check if there are different functional groups available on the molecule.

      • If there are free functional groups available for coupling, that won’t interfere with the binding site/epitope, they can be used to covalently couple the molecule to soft beads or biotin.
      • There are various types of soft beads that can bind different functional groups. For example, CM Sepharose couples via carboxymethyl group.
      • There are a wide range of biotinylation reagents available to target specific functional groups. For more information on biotinylation reagents go to LifeTechnologies.com and search “Thermo Scientific Avidin-Biotin Technical Handbook”.

      This article is also available on our website as Technology Note 222: Solid Phase Selection Guide.

      Bead Requirements

      Beads other than the ones listed in Table 1 can be used. Consider the following:

      • The beads must be >20 micron or they will not be retained in the flow cell.
      • Avoid fluorescent beads as they will affect the measurement.
      • Avoid magnetic beads as they absorb light and affect the measurement.
      Table 1: Commonly used solid phases and their requirements for KinExA instruments
      Solid Phase Type Particle Size Coating Method Molecule Quantity Molecule Requirements Instrument Sample Limits Coating Procedure
      Polystyrene Hard 98 µm Adsorption 30 µg >20 kDa ≤3 mL/min sample flow rate; ≤5 mL sample volume HG207
      Glass Hard 53-63 µm Adsorption 30 µg >20 kDa ≤3 mL/min sample flow rate; ≤5 mL sample volume HG207
      Streptavidin Coated Polystyrene Hard 98 µm Adsorption 15-30 µg Biotinylation ≤3 mL/min sample flow rate; ≤5 mL sample volume HG208
      Azlactone Soft 50-80 µm Covalent 10-20 µg Primary Amine (-NH2) ≤1 mL/min sample flow rate; ≤4 mL sample volume HG209
      Sepharose Soft 45-165 µm Covalent 10-20 µg Primary Amine (-NH2) ≤1 mL/min sample flow rate; ≤4 mL sample volume HG210
      CNBr-activated Sepharose Soft 45-165 µm Covalent 10-20 µg Primary Amine (-NH2) ≤1 mL/min sample flow rate; ≤4 mL sample volume Manufacturers Instructions
      CM Sepharose Soft 45-165 µm Covalent 10-20 µg Carboxymethyl (-CH2-COOH) ≤1 mL/min sample flow rate; ≤4 mL sample volume Manufacturers Instructions
      SulfoLink Soft 45-165 µm Covalent 10-20 µg Sulfhydryl (-SH) ≤1 mL/min sample flow rate; ≤4 mL sample volume Manufacturers Instructions

       

      Touring Idaho: Shoshone Falls

      Tucked away in Twin Falls, Idaho, Shoshone Falls—often called the “Niagara of the West”—is a breathtaking natural wonder. Towering at 212 feet and stretching 900 feet wide, it surpasses Niagara Falls in height, making it one of the largest natural waterfalls in the U.S. The falls, carved by the mighty Snake River through a striking basalt canyon on its journey to the Columbia River, offer a mesmerizing display of nature’s power. Plan your visit at 4155 Shoshone Falls Grade Road, Twin Falls, ID 83301, and prepare to be awestruck.

      The falls’ flow shifts dramatically with the seasons. Winter can bring a roaring 20,000 CFS (cubic feet per second) during heavy snowfall years, while spring—the ideal time to visit—delivers a steady 10,000 to 12,000 CFS as snowmelt surges through. In summer and fall, flows often decrease as water is diverted for irrigation, nourishing over 500,000 acres of farmland upstream. This vital water supports crops valued at $62 million annually, underscoring the Snake River’s role as a lifeline for the region’s economy. Whether you catch the falls at their thunderous peak or in quieter moments, Shoshone Falls promises an unforgettable experience. Add this gem to your travel list!

      Sapidyne Office Dogs: Scooby

      Meet Scooby, this playful corgi bounds into the office daily, wagging his tail and sparking joy. With zoomies down the hall and a love for naps, he’s a bundle of fun. His lovable charm shines through soulful eyes, making him the ultimate stress-buster. Scooby is a little dog with a big dog personality and he is happiest when he is doted on by his many fans.