Ion Torrent Sequencing: The DNA Reader That Skips Light

 

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Picture a DNA sequencer with no lasers.

No cameras.

No fluorescent dyes lighting up under a lens.

Sounds impossible, doesn't it?

After all, every sequencing platform we've covered so far has depended on light in one form or another.

Sanger sequencing detects fluorescently labelled fragments as they pass a laser near the end of a capillary.

Illumina images fluorescent nucleotides lighting up across the flow cell, one base at a time.

Pacific Biosciences captures flashes of light through a microscope as polymerase copies DNA inside microscopic wells.

Light, it seemed, was simply the price of admission.

But one team of engineers looked at that assumption and asked a different question.

Not "how do we build a better camera?"

But "do we even need one?"

What if, instead of watching DNA synthesis happen, we could listen to it instead?

Not with light.

With chemistry itself.

That question led to one of the strangest, most elegant DNA sequencers ever built.

Instead of detecting photons, it detects protons.

Welcome to the fascinating world of Ion Torrent sequencing.

Every DNA Polymerase Performs the Same Chemical Reaction

Before we can understand Ion Torrent sequencing, we first need to understand something DNA polymerase has been doing for billions of years.

DNA polymerase is the enzyme responsible for copying DNA.

As it moves along a DNA template, it adds complementary nucleotides to the growing strand.

A pairs with T.

G pairs with C.

Each incoming nucleotide arrives as a deoxyribonucleoside triphosphate (dNTP).

As we've discussed before, every dNTP consists of three parts:

• a nitrogenous base

• a deoxyribose sugar

• three phosphate groups

When DNA polymerase adds a nucleotide to the growing strand, a chemical reaction occurs.

The 3'-hydroxyl (3'-OH) group at the end of the strand attacks the α-phosphate of the incoming dNTP.

This forms the phosphodiester bond that joins the new nucleotide to the DNA.

Two phosphate groups leave together as pyrophosphate (PPi).

And one more thing happens.

A hydrogen ion (H⁺) is released.

That tiny ion slightly increases the acidity of the surrounding solution.

Normally, nobody pays attention to this proton. It's just a by-product.

The engineers behind Ion Torrent looked at it differently.

Instead of asking,

"How can we detect fluorescent light?"

they asked,

"Can we detect the proton instead?"

That single question changed everything.

Measuring Chemistry Instead of Light

Imagine watching DNA polymerase copy a molecule of DNA.

Suppose the next nucleotide the template calls for is A.

Supply DNA polymerase with dATP, and it's incorporated into the growing strand.

A hydrogen ion is released immediately after.

If the nucleotide doesn't match the template, nothing happens.

No nucleotide is added.

No proton is released.

No signal.

Every successful incorporation produces a tiny burst of acidity — and that burst is the signal.

Instead of watching for a flash of fluorescent light, Ion Torrent simply measures this tiny shift in pH.

The sequencing chemistry itself becomes the readout.

No dyes.

No lasers.

No cameras.

Just chemistry.

But There Was a Problem

The idea sounded elegant.

Unfortunately, there was one enormous obstacle.

One DNA molecule produces only one hydrogen ion per nucleotide incorporated.

That signal is incredibly small — far too small to measure reliably.

How could anyone detect something so tiny?

The answer wasn't a better sensor.

It was a bigger signal.

Amplifying the DNA

Unlike Pacific Biosciences and Oxford Nanopore, Ion Torrent isn't a single-molecule sequencing technology.

Every DNA fragment is amplified first.

The DNA is fragmented into smaller pieces.

Sequencing adapters are attached to each fragment.

Each fragment is then captured on the surface of a microscopic bead.

Next comes one of the most important steps in the entire workflow: emulsion PCR, or emPCR.

If you've never encountered it before, the concept is simpler than it sounds.

Imagine mixing oil and water together. Tiny droplets form throughout the mixture, and each droplet acts like its own miniature PCR tube.

Ideally, every droplet contains one bead, one DNA fragment, and PCR reagents.

PCR then takes place independently inside millions of these droplets.

Because each droplet started with only one DNA fragment, every copy made inside it is identical.

By the end of the reaction, each bead is coated with millions of identical copies of the same fragment.

Now the signal is strong enough to work with.

When nucleotide incorporation occurs, millions of DNA polymerase molecules release millions of hydrogen ions almost simultaneously — and suddenly, the pH change is large enough to detect.

Loading the Semiconductor Chip

The amplified beads are now ready for sequencing.

The chip contains millions of microscopic wells. Ideally, each well receives one bead, carrying one DNA template population.

Why only one bead?

Imagine placing two different DNA fragments into the same well.

One might incorporate an A. The other might incorporate a G.

Both reactions would release hydrogen ions at different times, and the signals would overlap. The instrument would have no way of knowing which fragment produced which signal.

One bead per well keeps every signal traceable to a single DNA fragment population.

Interestingly, not every well contains a bead. Some are intentionally left empty.

At first glance, that looks wasteful. In reality, these empty wells help measure background electrical noise and calibrate the chip throughout the run.

Sequencing One Nucleotide at a Time

Now the sequencing reaction begins.

Unlike Illumina, Ion Torrent introduces only one type of nucleotide at a time.

Suppose the instrument first flows dATP across every well.

If A is the correct nucleotide, DNA polymerase incorporates it, hydrogen ions are released, and the sensor detects the pH change.

If A isn't correct, nothing happens. The nucleotide is washed away.

Next comes dCTP. Then dGTP. Then dTTP.

The cycle repeats, over and over.

Because the instrument always knows which nucleotide is flowing at each step, it can read the DNA sequence simply by recording when a pH change occurs.

Signal during the G flow? The next base is G.

No signal at all? No nucleotide was incorporated during that cycle.

The Semiconductor Revolution

At this point you might be wondering: how does the instrument actually detect these tiny pH changes?

This is where Ion Torrent gets clever.

Instead of sitting beneath a microscope, every sequencing well sits directly above a tiny electronic sensor called an ion-sensitive field-effect transistor, or ISFET.

The name sounds intimidating. The idea isn't.

Most computer chips contain millions or billions of transistors that detect electrical signals. An ISFET is a specialised transistor designed to detect hydrogen ions instead.

As hydrogen ions accumulate in the well, the local pH shifts. That shift alters the transistor's electrical properties, converting a chemical signal directly into an electrical one.

No optical system required.

This is why Ion Torrent is often described as semiconductor sequencing. In many ways, the chip has more in common with a computer processor than with a microscope.

Reading the Electrical Signals

The instrument doesn't just check whether the pH changed.

It records the entire electrical signal over time — the baseline, the size of the peak, how quickly it rises, how it returns to baseline, and the background noise around it.

Only after processing all of that does the computer determine which nucleotide was incorporated.

This is called base calling.

Ion Torrent eliminated cameras and lasers. It replaced them with sophisticated electronic signal processing instead.

The Homopolymer Problem

For a while, everything sounds perfect.

Then we hit one of Ion Torrent's biggest challenges.

Imagine the DNA sequence contains:

AAAAAA

When the instrument introduces dATP, DNA polymerase doesn't stop after adding one A. It keeps going, A after A after A, until it reaches a different base.

In this example, six nucleotides are incorporated during a single flow — which means six times as many hydrogen ions are released.

Ideally, the signal should scale perfectly with length:

One A = signal of 1

Two As = signal of 2

Three As = signal of 3

In reality, the measurements look more like this:

One A = 1.0

Two As = 2.1

Three As = 3.0

Four As = 4.2

Five As = 5.1

Six As = 5.8

Seven As = 6.3

Eight As = 6.7

Watch what happens as the homopolymer gets longer.

The signal stops increasing in neat, even steps. Eventually the instrument struggles to tell whether it's looking at six nucleotides, seven, or eight.

This is the homopolymer problem, and it was one of Ion Torrent's major limitations.

DNA polymerase isn't making a mistake here. The limitation comes from trying to measure an analogue chemical signal that inevitably carries noise — the electronics just can't distinguish increasingly similar signal sizes with perfect precision.

A Familiar Workflow

If parts of the Ion Torrent workflow sound familiar, that's because they are.

Many of the early steps closely resemble 454 pyrosequencing: DNA fragmentation, adapter ligation, emulsion PCR, one fragment per bead, one bead per well.

The difference comes at the detection stage.

454 sequencing detects flashes of light produced by a cascade of enzymatic reactions. Ion Torrent skips the light entirely and measures the hydrogen ions released during DNA synthesis directly.

You can think of Ion Torrent as taking much of the workflow developed for 454 sequencing and swapping out the optical detection system for semiconductor electronics.

Why Is It Called Ion Torrent?

The name is fairly descriptive, even if the exact story behind it isn't well documented.

Ion clearly refers to the hydrogen ions being detected during DNA synthesis — that part is unambiguous.

Torrent is the more evocative half. The most natural reading is that it nods to the flood of sequencing data pouring off millions of wells simultaneously — and that interpretation fits the technology well, even if it isn't something the company has spelled out on record.

Either way, the name has aged well. Nine years after launch, it still describes exactly how the technology works.

The Advantages of Ion Torrent

Ion Torrent introduced several important innovations.

By eliminating fluorescent dyes and optical detection, the instruments became mechanically simpler. No lasers. No fluorescence filters. No mirrors. No complex optical alignment. No high-resolution cameras.

Sequencing relied almost entirely on semiconductor electronics instead — which meant improvements in chip manufacturing could, in principle, improve sequencing performance over time too.

The chemistry itself was refreshingly straightforward. Unlike Illumina, Ion Torrent doesn't require fluorescent nucleotides or reversible terminators. It simply uses ordinary dNTPs, and the polymerase behaves much as it would inside a living cell.

The Limitations

Like every sequencing technology, Ion Torrent has its weaknesses.

Its biggest one is accurately calling the length of long homopolymer regions.

It also produces much shorter reads than long-read platforms like Pacific Biosciences and Oxford Nanopore. Excellent for many targeted sequencing applications — less suited to anything that needs long, contiguous DNA reads.

The Legacy of Ion Torrent

When Ion Torrent launched in 2010, it represented a completely different way of thinking about DNA sequencing.

For decades, sequencing had grown increasingly dependent on optics. Ion Torrent went the other way — it removed optics almost entirely.

Instead of asking, "What colour of light did we observe?" it asked, "Did DNA synthesis release a proton?"

That sounds like a small change. In reality, it transformed the engineering philosophy behind DNA sequencing.

Sometimes scientific breakthroughs don't come from inventing new chemistry. They come from looking at familiar chemistry differently.

Biochemists had known for decades that DNA polymerase releases a hydrogen ion with every incorporation. Most people ignored it.

The engineers behind Ion Torrent built an entire sequencing platform around it.

Related Content

• Sanger sequencing https://adwoabiotech.blogspot.com/2026/06/sanger-sequencing-explained-how-one.html: The Original DNA Reader — Before semiconductors and pH meters, there was chain termination and capillary electrophoresis. See where it all started.

• Illumina sequencing https://adwoabiotech.blogspot.com/2026/06/what-is-next-generation-sequencing-ngs.html: Watching DNA Synthesis in Real Time — The optical, fluorescence-driven platform Ion Torrent set out to do without.

• Oxford Nanopore  [https://adwoabiotech.blogspot.com/2026/06/pacbio-smrt-sequencing-vs-oxford.html: Reading DNA One Molecule at a Time — Single-molecule, real-time sequencing through zero-mode waveguides — no amplification required.

• Pacific Biosciences https://adwoabiotech.blogspot.com/2026/06/what-is-oxford-nanopore-sequencing-how.html: Sequencing Through a Tiny Pore — The long-read platform that ditched optics and amplification.

PacBio SMRT Sequencing vs Oxford Nanopore: A Beginner's Guide to Long-Read DNA Sequencing

 Pacific Biosciences vs Oxford Nanopore: The Story of How Scientists Learned to Read Long DNA Molecules

Welcome to Adwoa Biotech, where we make biological sciences clear and fun.

If you've been following the evolution of DNA sequencing, you've already seen how scientists went from the painstaking days of Sanger sequencing to the high-throughput revolution of next-generation sequencing (NGS). Sequencing that once took days could now be completed in hours, and instead of sequencing a single DNA fragment at a time, millions could be sequenced simultaneously.

It sounded like the perfect solution.

But there was a still room for optimisation. The instruments that enabled millions of sequencing to be performed simultaneously, could only do so with short fragments (150 to 300 base pairs).

While this dramatically increased throughput and reduced cost, it introduced an entirely new challenge. Scientists were no longer reading long stretches of DNA. Instead, they were breaking genomes into millions or even billions of tiny fragments and relying on computers to piece them back together.

Imagine receiving a novel after someone had shredded every page into tiny strips containing only a few words each. You could probably reconstruct many of the sentences. But if the novel contained repeated paragraphs, missing pages, or similar-looking chapters, putting everything back together correctly would become incredibly difficult.

DNA presents exactly the same problem.

Large genomes are full of repetitive DNA sequences. The human genome, for example, is nearly 3.2 billion base pairs long, and almost half of it consists of repetitive elements. If your sequencing reads are only 150 base pairs long, many reads may map equally well to multiple locations within the genome. The computer simply cannot determine where some fragments belong.

This made assembling complete genomes difficult. Structural variants such as large insertions, deletions, inversions, and chromosomal rearrangements were often missed. Highly repetitive regions remained unresolved. Some medically important genes were impossible to assemble accurately.

Scientists needed a way to read much longer pieces of DNA.

Interestingly, two companies approached this challenge in completely different ways.

One company asked:

What if we watched DNA polymerase copy DNA one nucleotide at a time?

The other asked:

What if we didn't copy the DNA at all?

Those two ideas gave rise to two of the most important sequencing technologies available today: Pacific Biosciences' Single Molecule Real-Time (SMRT) sequencing and Oxford Nanopore sequencing.

Although both technologies are classified as long-read sequencing methods, the way they work could hardly be more different.

Pacific Biosciences: Watching DNA Polymerase at Work

Our story begins in the early 2000s.

Scientists had already spent decades studying DNA polymerase, the remarkable enzyme responsible for copying DNA inside every living cell.

Every time a cell divides, DNA polymerase faithfully adds complementary nucleotides to a growing DNA strand.

A pairs with T.

G pairs with C.

Scientists wondered whether this natural process itself could become the sequencing instrument.

Instead of stopping DNA synthesis like Sanger sequencing, or sequencing millions of amplified DNA fragments simultaneously like second-generation sequencing, why not simply watch a single DNA polymerase molecule doing what intelligent design designed it to do?

This became the foundation of Single Molecule Real-Time sequencing, more commonly known as SMRT sequencing.

The name is actually very descriptive.

Single Molecule means that each DNA molecule is sequenced individually without requiring clusters of identical DNA molecules.

Real-Time means the sequencing instrument observes DNA synthesis as it happens.

But this immediately created another problem.

DNA polymerase is an incredibly tiny enzyme. Individual nucleotide incorporation events occur within milliseconds. Even with the world's most sensitive microscopes, how could anyone observe a single enzyme working?

This is where Pacific Biosciences introduced one of the most elegant engineering solutions in modern biotechnology.

Zero-Mode Waveguides: Shrinking the Observation Window

The answer was not to build a better microscope.

Instead, they built a smaller observation chamber.

PacBio developed microscopic structures called Zero-Mode Waveguides, often abbreviated as ZMWs.

A ZMW is an extremely tiny hole etched into a metal film deposited on a glass chip.

These holes are far smaller than the wavelength of visible light.

Normally, light spreads throughout a sample, causing enormous background fluorescence.

Inside a ZMW, however, light cannot propagate normally.

Instead, only an incredibly thin region at the very bottom of the well becomes illuminated.

Think of shining a flashlight into an enormous room versus shining it through the eye of a needle.

Only a tiny volume becomes visible.

This tiny illuminated volume is where the magic happens.

A single DNA polymerase molecule is immobilised at the bottom of each ZMW.

The DNA template is attached to that polymerase.

Everything else remains effectively invisible.

Now scientists could watch one DNA polymerase molecule copying one DNA molecule without being overwhelmed by background fluorescence.

Fluorescent Nucleotides

Next, the polymerase needs nucleotides to build the new DNA strand.

Unlike Sanger sequencing, PacBio does not use chain-terminating nucleotides.

Instead, it uses normal nucleotides carrying fluorescent dyes.

Each of the four nucleotides has its own fluorescent colour.

A emits one colour.

T another.

G another.

C another.

Importantly, the fluorescent dye is attached to the phosphate group rather than the nucleotide base itself.

Why?

Because DNA polymerase naturally removes the phosphate groups during DNA synthesis.

When the nucleotide is incorporated, the fluorescent label is automatically cleaved away and diffuses out of the observation chamber.

The newly synthesised DNA therefore remains completely natural.

This allows the polymerase to continue synthesising DNA uninterrupted for thousands of nucleotides.

Watching DNA Being Copied

Now the sequencing reaction begins.

DNA polymerase selects the next complementary nucleotide.

As that nucleotide briefly sits inside the enzyme before incorporation, its fluorescent dye remains within the illuminated region of the ZMW.

The instrument records a short flash of coloured light.

Once incorporation occurs, the fluorescent label is released.

The light disappears.

Another nucleotide enters.

Another flash occurs.

By recording thousands of these flashes every second, the instrument reconstructs the DNA sequence one nucleotide at a time.

Unlike previous sequencing technologies, PacBio is literally watching DNA synthesis in real time.

But There Was Another Problem

Single-molecule sequencing was ground breaking.

Unfortunately, early versions were not particularly accurate.

Every sequencing technology makes occasional mistakes.

When only one molecule is observed, random errors become much more noticeable.

PacBio needed a way to improve accuracy without sacrificing long read lengths.

The solution was surprisingly clever.

Instead of reading the DNA molecule once...

they decided to read it again.

And again.

And again.

Circular Consensus Sequencing

PacBio converts each DNA fragment into a circle before sequencing.

Special DNA adapters are attached to both ends of the fragment, creating a circular molecule known as a SMRTbell template.

Because the DNA is circular, DNA polymerase simply keeps moving around the same insert multiple times.

Imagine proofreading the same sentence repeatedly.

If you read it once, you might miss a typo.

If you read it ten times, mistakes become much easier to identify.

PacBio applies exactly the same principle.

Each pass around the circular DNA generates another observation of the same sequence.

The instrument combines all these observations into a single consensus sequence.

This approach became known as Circular Consensus Sequencing (CCS).

The resulting reads are called HiFi reads because they combine long read lengths with extremely high accuracy, often exceeding 99.9%.

Today, HiFi sequencing is one of PacBio's defining strengths.

Reading More Than Just DNA Sequence

PacBio's polymerase provides another useful source of information.

DNA polymerase does not move at exactly the same speed across every DNA molecule.

Certain chemical modifications, particularly DNA methylation, cause the polymerase to hesitate slightly before incorporating the next nucleotide.

These subtle changes in incorporation timing can be measured.

Although PacBio is primarily a sequencing platform, it can also detect several DNA modifications by analysing polymerase kinetics.

The Strengths of PacBio

PacBio rapidly became one of the preferred technologies for applications requiring extremely accurate long reads.

Researchers use it for:

• High-quality genome assembly

• Structural variant detection

• Sequencing difficult genomic regions

• Full-length transcript sequencing

• Haplotype phasing

• Clinical research requiring highly accurate long reads

Its biggest strength is simple.

Few sequencing technologies produce reads that are simultaneously long and exceptionally accurate.

Oxford Nanopore Asked a Completely Different Question

While PacBio was perfecting fluorescent sequencing, another group of scientists was thinking very differently.

They asked:

Why copy DNA at all?

After all, DNA already contains the information.

Perhaps the molecule itself could simply be read directly.

This became the foundation of Oxford Nanopore sequencing.

Instead of watching DNA polymerase build a copy, Oxford Nanopore measures the original DNA molecule itself.

What Is a Nanopore?

A nanopore is exactly what its name suggests.

It is an extremely tiny pore only a few nanometres wide.

The pore is formed by a protein embedded within an artificial membrane.

An electrical voltage is applied across the membrane.

This creates a flow of ions through the nanopore, producing a steady electrical current.

Initially, the current remains constant.

Then DNA enters the pore.

Everything changes.

DNA Interrupts the Electrical Current

DNA carries a negative charge because of its phosphate backbone.

When a DNA molecule enters the nanopore, it partially blocks the movement of ions.

The electrical current immediately changes.

Importantly, different combinations of DNA bases obstruct the pore differently.

The nanopore is actually sensing several neighbouring bases simultaneously rather than one nucleotide at a time.

Each group of bases produces its own characteristic electrical signature.

The sequencing instrument continuously records these tiny changes in current thousands of times every second.

Controlling the Speed

At first glance this sounds simple.

But there was another problem.

DNA moves far too quickly.

If allowed to pass freely through the nanopore, the molecule would move so rapidly that meaningful measurements would be impossible.

Oxford Nanopore solved this using another biological enzyme.

A specialised motor protein grabs the DNA and feeds it through the nanopore one small step at a time.

This slows DNA movement sufficiently for the electrical signal to be measured accurately.

Without the motor protein, nanopore sequencing would not work.

Turning Electrical Signals into DNA Sequence

Unlike PacBio, Oxford Nanopore never observes fluorescent light.

Instead, it records one long electrical signal.

The challenge becomes interpreting that signal.

Sophisticated machine learning algorithms analyse the changing current and determine which DNA bases most likely produced each electrical pattern.

This computational process is known as basecalling.

As sequencing chemistry and artificial intelligence have improved, nanopore sequencing accuracy has increased dramatically.

Reading Native DNA and RNA

One of Oxford Nanopore's biggest advantages is that the DNA molecule does not need to be copied.

The original molecule passes directly through the nanopore.

This means researchers can sequence native DNA.

Even more remarkably, Oxford Nanopore can also sequence native RNA directly.

Most sequencing technologies require RNA to be converted into complementary DNA (cDNA) before sequencing.

Nanopore sequencing can often bypass this step entirely.

Detecting DNA Modifications

Because Oxford Nanopore measures the physical properties of the DNA molecule itself, chemical modifications alter the electrical current.

This means methylated DNA produces a different signal from unmethylated DNA.

Researchers can therefore identify many DNA modifications directly during sequencing without requiring additional chemical treatments.

This has made nanopore sequencing particularly valuable for epigenetics research.

Ultra-Long Reads

Perhaps the most famous feature of Oxford Nanopore sequencing is its read length.

In theory, the nanopore does not limit how long a DNA molecule can be.

As long as high-quality DNA can be extracted without breaking, the molecule can continue passing through the pore.

Researchers have generated sequencing reads exceeding one million base pairs in length.

These ultra-long reads are invaluable for assembling highly repetitive genomes that were previously impossible to resolve.

The Strengths of Oxford Nanopore

Oxford Nanopore has carved out a unique position in DNA sequencing.

Its major strengths include:

• Ultra-long sequencing reads

• Direct sequencing of native DNA

• Direct sequencing of native RNA

• Detection of DNA modifications

• Portable sequencing instruments

• Real-time data generation

Perhaps its most recognisable instrument is the MinION, a pocket-sized sequencer small enough to fit in the palm of your hand.

Researchers have used it in remote rainforests, during infectious disease outbreaks, aboard the International Space Station, and in field hospitals where traditional sequencing laboratories simply do not exist.

PacBio vs Oxford Nanopore

Although both technologies generate long reads, they solve the sequencing problem in fundamentally different ways.

PacBio watches DNA polymerase synthesise a new DNA strand.

Oxford Nanopore measures the original DNA molecule passing through a nanopore.

PacBio relies on fluorescent light.

Oxford Nanopore relies on electrical current.

PacBio obtains exceptional accuracy by repeatedly sequencing the same circular DNA molecule to generate HiFi consensus reads.

Oxford Nanopore achieves extraordinary read lengths because the DNA molecule itself passes continuously through the nanopore.

PacBio is generally preferred when the highest possible sequence accuracy is required.

Oxford Nanopore is often preferred when ultra-long reads, portability, direct RNA sequencing, or epigenetic analysis are the primary goals.

Neither technology is universally better.

Each was designed to solve a different problem.

The Future of Long-Read Sequencing

For many years, scientists believed they had to choose between long reads and accurate reads.

Today, that distinction is becoming less clear.

PacBio continues to improve the accuracy and throughput of HiFi sequencing.

Oxford Nanopore continues to improve its nanopore chemistry, pore design, motor proteins, and machine learning basecalling algorithms.

Both technologies are becoming faster, more accurate, and more affordable every year.

Together, they are allowing scientists to study regions of the genome that were previously inaccessible, discover structural variants that short-read sequencing often misses, characterise complex epigenetic modifications, assemble complete genomes with unprecedented accuracy, and even sequence DNA outside traditional laboratories.

The story of long-read sequencing reminds us that there is often more than one solution to the same scientific problem.

Related Reading

New to sequencing technologies? Start with Sanger Sequencing Explained: How One of the Oldest DNA Sequencing Methods Still Works to understand the foundational method that long-read platforms eventually built on. 

If you want to see how short-read NGS stacks up against Sanger, check out What Is Next-Generation Sequencing? NGS vs Sanger Explained. 

And for a closer look at how Nanopore sequencing compares to the original Sanger method, read What Is Oxford Nanopore Sequencing? How It Differs from Sanger.