In life science experiments, there is a seemingly simple yet crucial operation: transferring a barely visible bacterial colony from the agar surface of a petri dish precisely into a liquid culture medium in another container.

This action is repeated hundreds or thousands of times daily by microbiologists. Over seventy years, the tools and methods used have undergone six major evolutions — each addressing the same core challenge: How to sample and transfer colonies faster, more accurately, and more cleanly.

In this article, we attempt to trace the origins and developments of these six generations of technology. No judgments, just documentation. Let us begin with a toothpick.

Manual Picking Era: Toothpicks, Inoculation Loops, and Human Hands

1950s - Present (still widely used)

The most primitive and classic method. A technician sits at a laminar flow hood, holding a sterilized toothpick or platinum inoculation loop in one hand and stabilizing the petri dish with the other, carefully picking individual colonies near an alcohol lamp and transferring them to test tubes or well plates.

Platinum loops can be sterilized by flaming and reused; disposable plastic loops and sterile toothpicks are discarded after use. Some labs even drop the toothpick directly into the liquid culture tube, leaving both the toothpick and colony in the medium — this is the earliest prototype of the "sampling tool transfers with sample" concept.

Speed: ~300/hour (skilled operator)
Highly manual, prone to fatigue errors

Representative tools: Platinum inoculation loop, disposable plastic loops, sterile toothpicks, sterile bamboo sticks

Reusable Metal Needle Era: The Dawn of Robotic Picking

1990s - Present

With the advancement of the Human Genome Project (HGP), throughput demands for colony picking exploded. Manual operations could no longer meet the need for picking tens of thousands of colonies daily, giving rise to automated colony pickers.

The core idea of this generation: Replace human hands with robots, replace toothpicks with metal needles. Equipment captures images of petri dishes via CCD cameras, software automatically identifies colony positions, then robotic arms drive metal needles (typically tungsten alloy, 96 in parallel) to precisely dip colonies and transfer them to 96-well target plates.

To address cross-contamination, metal needles undergo a complete cleaning and disinfection process after each pick: multiple ethanol soaks → halogen lamp high-temperature drying → cooling wait. While ensuring safe reuse, this disinfection process became a speed bottleneck — approximately 62% of each cycle was spent on cleaning.

Nominal speed: ~3,000/hour
Cleaning: 6 ethanol washes + halogen lamp
Actual throughput significantly lower than nominal

Representative product: Molecular Devices QPix series (1990s-present, over 600 installations worldwide)

Disposable Needle/Tip Era: Sterility Through Discarding

2000s - Present

While effective, the second generation's cleaning process always carried risks: incomplete cleaning leads to cross-contamination. Thus another school of thought emerged in the industry — Simply don't clean, discard after use.

This generation uses disposable needles or plastic tips instead of reusable metal pins. A new needle is used for each colony pick, eliminating cross-contamination at its source. SCARA robots with automatic tip ejection mechanisms can eject old tips and install new ones after each pick.

The tradeoff is significantly higher consumable costs, and the mechanical action of tip ejection/replacement also takes time. Some equipment uses pipette tips to aspirate bacterial suspensions directly, but with lower throughput.

Zero cross-contamination (disposable)
High consumable costs
Tip ejection/replacement time consuming

Representative products/solutions: Chinese Patent CN213529686U (disposable needle + SCARA robot), Hudson RapidPick Harvester (pipette tip style), Sartorius PrecisionTips

Continuous Polymer Wire Cutting Era: Always a New Tip

2010s - Present

UK-based Singer Instruments proposed an ingenious compromise: instead of repeatedly cleaning the same needle or replacing individual disposable needles, use a continuous spool of polymer wire, cutting a new surface each time.

This consumable, called PickupLine™, is a 1mm diameter specially formulated polymer extruded wire, loaded into the device as a 200-meter spool. Before each pick, precision blades inside the device cut a brand new clean surface, which is then used to dip and transfer the colony. A 200-meter spool can produce over 33,000 disposable sampling surfaces.

This design cleverly balances cost and sterility — consumable costs are far lower than individual disposable needles, while always using a fresh surface eliminates cleaning needs. However, it fundamentally remains a "point contact + contact transfer" mode.

Speed: ~3,000/hour
Disposable new surface, no cleaning required
Low consumable cost (33,000 picks per spool)
Still point contact, still requires "separation" step

Representative product: Singer Instruments PIXL / PIXL Max (over 1,000 installations worldwide, covering 60 countries)

Non-Contact Laser Microfluidic Era: Picking Without Touching

2020s - Cutting Edge Research

While the first four generations focused on "what tool to use to touch the colony," the fifth generation completely breaks this framework — it doesn't touch the colony at all.

The Digital Colony Picker developed by the Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, uses microfluidic chips instead of traditional petri dishes, isolating single microbial cells in 16,000 picoliter microchambers. After AI image recognition locks onto targets, laser-induced bubble technology "retrieves objects remotely," exporting target microbes as microdroplets.

This is currently the most cutting-edge technological approach, offering single-cell resolution and zero contamination. However, it requires specialized microfluidic chips (high cost), is incompatible with traditional petri dishes, and has relatively limited throughput — currently better suited for research than industrial production.

Zero contamination (non-contact)
Speed: ~1,000/hour
Incompatible with traditional petri dishes
High chip cost

Representative product: Digital Colony Picker (Qingdao Institute of Bioenergy/CAS / Qingdao Starsay Biotech, published in Nature Communications 2025)

Sampling Ball Drop Era: No Separation, No Cleaning, No Waiting

2023 - Present

Reviewing the first five generations reveals an interesting pattern: they all struggled to varying degrees with the same problem — "Separation of sampling tool from colony".

The first generation pulled out the toothpick by hand, the second cleaned away residues, the third ejected the needle, the fourth cut away the old surface, and the fifth eliminated physical tools entirely. Regardless of approach, the "separation" step consumed time or cost.

The sixth generation takes a completely different path: No separation.

The sampling ball drop transfer technology uses a tiny sphere (~2mm diameter) sterilized through 8 processes. After being picked up by a pneumatic pen, the sphere's surface dips the colony from the petri dish, then the sampling ball along with the colony is dropped directly into the target liquid medium. The ball stays in the liquid — no removal, no cleaning, no post-processing required. Release one ball, immediately pick up the next new ball, zero waiting in between.

This idea seems simple even "brutal" at first — but it fundamentally eliminates the speed bottleneck that plagued the first five generations. When 62% of cycle time (cleaning and disinfection) is reduced to zero, an order-of-magnitude speed leap naturally occurs.

The accompanying rapid imaging inspection system performs four quality checks on each sampling ball before picking (pickup confirmation, integrity check, cleanliness check, image traceability), and a dual QR code matching system enables precise sampling tracking — all completely new requirements that didn't exist in previous generations.

Sampling balls have evolved into multiple materials: glass balls (frosted surface for increased bacterial adhesion), steel balls (high density for stable sinking), dissolvable balls (leave no residue after dissolution), allowing different customers to choose based on biological requirements.

Actual throughput: ≥3,000/hour (SAT verified)
Disposable, zero cross-contamination
Extremely low consumable cost

Representative product: Qingdao Gongfa Intelligent Generation II Colony Sampling Workstation (purchased by multiple leading gene synthesis companies, passed SAT verification, applied for domestic invention patent and PCT international patent)

Across all six generations, a clear evolutionary thread emerges: the industry has continuously sought better ways to solve the "post-processing of sampling tools" problem.

Gen I: Manual flame sterilization → Gen II: Machine automatic cleaning → Gen III: Stop cleaning, replace entirely → Gen IV: Replace wire segment instead of whole needle → Gen V: Eliminate physical tools → Gen VI: Use physical tool, but don't retrieve it.

Each generation attempted to reduce "post-processing" time. The sixth generation's breakthrough lies not in making post-processing faster, but in making the concept of post-processing disappear entirely.

Looking back at seventy years of technological evolution, perhaps the most striking observation is: Change is never driven by complex theoretical breakthroughs, but by repeatedly asking a simple question — "Can it be simpler?"

In the first generation's toothpick method, some technicians habitually dropped the colony-dipped toothpick directly into the culture tube — this most "lazy" approach unintentionally became the conceptual prototype for the sixth generation's sampling ball technology. Yet, from "manual toothpick tossing" to "robotic automatic deployment of 8-step sterilized sampling balls," seventy years and five generations of technology lay in between.

"The best tool is the one you forget exists. The moment the sampling ball enters the culture medium, the tool disappears. Disappearance is its perfect state."

The evolution of colony sampling technology continues. Perhaps there will be seventh and eighth generations in the future. But regardless of technological advancements, the core goal remains unchanged: moving one colony from here to there — faster, more accurately, more cleanly.

Six generations, seventy years of pursuit — all for this one small thing.

Product information and parameter data for each generation in this article are sourced from publicly available product manuals, academic papers, and patent documents, including but not limited to: Molecular Devices QPix Colony Picking Series Brochure, Singer Instruments PIXL Specifications, Nature Communications (2025) AI-powered Digital Colony Picker, Chinese Patent CN213529686U, Chinese Patent CN117305088A, etc. This article aims to objectively document the industry's technological evolution and does not represent evaluation of any specific product.