{"id":1867,"date":"2025-11-17T11:34:29","date_gmt":"2025-11-17T11:34:29","guid":{"rendered":"https:\/\/chromocan.test\/technology\/capturesmb\/"},"modified":"2026-05-11T09:36:55","modified_gmt":"2026-05-11T07:36:55","slug":"capturesmb","status":"publish","type":"technology","link":"https:\/\/www.chromacon.com\/en\/technologies\/capturesmb\/","title":{"rendered":"Continuous Capture (CaptureSMB\u00ae)"},"content":{"rendered":"
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\n TWIN-COLUMN CAPTURE <\/p>\n \n

\n Continuous Capture Chromatography with CaptureSMB\u00ae<\/strong>\n <\/h1>\n \n
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Load to Full Capacity.<\/strong> Continuous capture with twin-column periodic countercurrent chromatography. The simplest PCC configuration on the market. Validated by Bristol Myers Squibb from lab to 100\u00d7 scale: 2.5\u00d7<\/strong> Productivity | 92%<\/strong> Resin utilisation (vs. 67% batch) | 50%<\/strong> less buffer | \u226594%<\/strong> Yield maintained<\/p>\n

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Source: Angelo et al., BioProcess International 2018; M\u00fcller-Sp\u00e4th et al., Biotechnol. Bioeng. 2019 (Bristol Myers Squibb)<\/em><\/strong><\/p>\n <\/div>\n <\/div>\n\n

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\n Request a Webinar<\/span><\/a><\/span> <\/div>\n
\n CaptureSMB Scale-Up Paper<\/span><\/a><\/span> <\/div>\n <\/div>\n <\/div>\n <\/div>\n\n
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\n Request a Webinar<\/span><\/a><\/span> <\/div>\n
\n CaptureSMB Scale-Up Paper<\/span><\/a><\/span> <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n
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\n The Capture Bottleneck <\/h2>\n \n
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In batch affinity capture, every loading decision is governed by the same constraint: avoid product break through. The result is a conservative safety margin \u2014 columns loaded to 50\u201370% of their dynamic binding capacity to avoid the risk of any product loss at the column outlet.<\/p>\n

That conservative margin is expensive. Protein A resin costs thousands of dollars per liter \u2014 up to $16,000\/L for premium resins \u2026 and other affinity resins are even more expensive. Loading to 60% of capacity means 40% of your resin is idle every cycle. At the same time, the fastest loading flow rates that maximize productivity produce shallow breakthrough curves \u2014 which force even more conservative loading margins. The harder you push for throughput, the lower your resin utilization becomes.<\/p>\n

For large molecules like monoclonal antibodies and AAV capsids, this tradeoff is especially pronounced. Their low diffusivity means breakthrough curves are inherently shallow at practical flow rates, making high resin utilization and high productivity genuinely incompatible on a single column.<\/p>\n <\/div>\n \n <\/div>\n\n

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CaptureSMB\u00ae Changes the Equation<\/h2>\n\n\n
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CaptureSMB\u00ae<\/strong> removes the constraint that makes the tradeoff unavoidable. Instead of stopping loading when product starts to break through the upstream column, it lets loading continue \u2014 and places a second column immediately downstream to capture whatever breaks through.<\/p>\n

The upstream column is loaded beyond its dynamic binding capacity. Product that would be lost in batch is captured on the downstream column. When the upstream column is fully saturated, it is washed and the product is collected. Then columns switch positions: the former downstream column \u2014 now preloaded with captured product \u2014 becomes the new upstream column, while the former upstream column gets ready to capture the breakthrough from the new upstream column.<\/p>\n\n \n <\/div> \n\n\n

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\n 2.5\u00d7 <\/h2>\n \n

\n Productivity increase vs. batch Protein A <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n 92% <\/h2>\n \n

\n Resin utilization vs. 67% batch <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n 50% \u2193 <\/h2>\n \n

\n Buffer reduction vs. batch process <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n\n\n\n

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\n \u226594% <\/h2>\n \n

\n Yield equivalent to batch <\/p>\n \n \n <\/div>\n\n<\/div>\n\n <\/div><\/section><\/div>\n<\/div>\n\n\n

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BMS-validated at 100\u00d7 scale \u2014 Contichrom\u00ae CUBE to TWIN. Angelo et al., BioProcess International, 2018.<\/em><\/strong><\/a><\/p>\n

Two columns are all it takes. Other periodic counter-current (PCC) systems use three, four, or more columns to achieve high resin utilisation \u2014 adding valve complexity, scheduling constraints, and additional method development effort. CaptureSMB demonstrates that a two-column counter-current design delivers the full performance benefit with the simplest possible hardware and the shortest path from batch method to running process.<\/p>\n\n \n <\/div> <\/div>\n<\/div>\n\n\n

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\n How CaptureSMB\u00ae Works <\/h2>\n \n
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Each CaptureSMB\u00ae cycle consists of two switches, one elution from each column per cycle. Within each switch, three phases run in sequence:<\/p>\n\n\n\n\n\n\n\n
Phase<\/th>\nUpstream column<\/th>\nDownstream column<\/th>\n<\/tr>\n<\/thead>\n
Interconnected Loading<\/strong><\/td>\nFeed loaded at high flow rate beyond DBC \u2014 breakthrough flows through to downstream column<\/td>\nReceives breakthrough from upstream column; product captured (preload)<\/td>\n<\/tr>\n
Interconnected Wash<\/strong><\/td>\nEquilibration buffer flushes the liquid phase from upstream column through to downstream column \u2014 remaining product captured<\/td>\nCaptures product flushed from upstream column void volume<\/td>\n<\/tr>\n
Batch Phase<\/strong><\/td>\nFormer downstream column loaded at lower batch flow rate \u2014 regenerated column not yet ready<\/td>\nFormer upstream column: washed, eluted (product collected), CIP, re-equilibrated in parallel<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
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At the end of the batch phase, the columns switch positions by valve \u2014 the former downstream column (now preloaded and freshly loaded in batch) becomes the upstream column for the next switch. The cycle repeats indefinitely until the feed is consumed or the process is stopped.<\/p>\n

A short Startup<\/strong> phase precedes the cyclic stage: both columns are loaded together to the DBC with columns interconnected, ensuring the downstream column carries a preload equivalent to a steady-state cycle before the first switch. This means cyclic steady state is reached immediately \u2014 typically by cycle 2.<\/p>\n

The Shutdown<\/strong> stage elutes the former downstream column that was not fully processed in the last batch phase, recovering the remaining product.<\/p>\n<\/div>\n <\/div>\n \n <\/div>\n\n

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The CaptureSMB Process Principle (.pptx)<\/p>\n <\/div>\n <\/div>\n <\/section>\n\n<\/section>\n\n

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Method Design with the CaptureSMB\u00ae Wizard<\/h2>\n

CaptureSMB methods are designed in the CaptureSMB\u00ae Wizard<\/strong> in ChromIQ\u00ae 9 \u2014 a tab-based interface that takes breakthrough curve data from the Contichrom\u00ae CUBE and generates a complete, ready-to-run method. The CaptureSMB Wizard starts from breakthrough curve (BTC) data<\/strong> \u2014 the measured column outlet concentration as the column is loaded to saturation.<\/p>\n <\/div>\n \n

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\n Step 1 \u2014 Run a breakthrough curve experiment on the CUBE <\/h3>\n
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Before opening the wizard, run a single-column breakthrough curve experiment on the Contichrom\u00ae CUBE at the target residence time. Load the column to at least 70% breakthrough, collecting 10\u201315 fractions for offline concentration analysis.<\/p>\n

The single run data is the main input required \u2013 no additional experimental batch runs are needed.\u00a0The Tutorial tab in the wizard summarises the BTC requirements and recommended residence times for your resin particle size.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n

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\n Step 2 \u2014 Enter column and BTC data in the Loading tab <\/h3>\n
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In the Loading<\/strong> tab, enter feed titer, column dimensions, and loading velocity. Enter the BTC data points (loaded volume in mL vs. breakthrough concentration in g\/L) from your offline fraction analysis. Select the appropriate BTC correlation function (e.g., Monoclonal Antibody for Protein A processes) \u2014 the wizard fits the curve and displays the estimated static binding capacity and projected capacity utilisation. All subsequent calculations to determine loading parameters and simulate process performance are derived from this fitted curve.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n

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\n Step 3 \u2014 Configure washing, elution, and regeneration <\/h3>\n
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In the Recovery & Regeneration<\/strong> tab, enter the steps for your post-load wash, elution, CIP, and re-equilibration protocol \u2014 the same sequence used in your existing batch process. Volume, flow rate, and buffer assignment per pump inlet are set here. The wizard uses these durations to calculate the batch loading flow rate, ensuring the downstream column completes loading within the available regeneration window.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n

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\n Step 4 \u2014 Review performance prediction, activate AutomAb\u00ae, and generate <\/h3>\n
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The Method Settings & Performance<\/strong> tab shows predicted process performance before a single CaptureSMB\u00ae run: productivity (g\/L\/h), buffer consumption (L\/g), capacity utilisation (%), pool concentration (g\/L), cycle time, and switch time. Activate AutomAb\u00ae dynamic process control here (see below). Set the number of cycles, then hit Save<\/strong> \u2014 the wizard generates Startup, Main, Shutdown, and procedure files, ready to run from the ChromIQ\u00ae Procedure tab.<\/p>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n\n \n

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