Flow cytometry · Intelligent Material

Every cell carries a code.

Rare-earth crystals turn a cytometer label into a code: which ion emits, how fast it rises, how long it glows and which lasers wake it. Excited at 980 nm, below most autofluorescence, they give narrow lines, little spillover and very little photobleaching.

See the code spaceBuild a panel with us
SHEATHSAMPLE365 nm800 nm980 nm1550 nmGATEDDETECTORSLIVE DOT PLOTemission colorlifetimePULSES · rise / decay
Illustration: four laser spots, gated detectorsCells flash only for the lasers their crystal answers
980 nmnear-infrared excitation, below most cellular autofluorescence
7×7×3emitters, lifetimes and rise times: 147 single-crystal codes
µs–msglow lifetimes, read by time-gated detectors
Stableinorganic crystals are highly resistant to photobleaching

Why a new reporter

Color runs out. Codes don't.

Conventional dyes emit broad, overlapping bands, so every new color leaks into its neighbors and has to be compensated. Crystal emitters give narrow lines, and lifetime and rise time add dimensions that color alone cannot.

CONVENTIONAL DYESbroad, overlapping emissionSPILLOVERcompensationneededIMS CRYSTALSnarrow emission linesSPILLOVERalmost noneneeded
01

Low background

980 nm light excites very little in cells and plastics, so the dark stays dark.

02

Narrow lines

Rare-earth emission lines are sharp, so detector channels barely overlap.

03

Time as a parameter

Microsecond-to-millisecond glow lets a gated detector tell crystals apart by timing as well as color.

Optical code space · Flow cytometry and beyond

Seven emitters. Seven lifetimes. Three rise times.

Color alone runs out fast. Intelligent Material crystals carry several independent signals at once: which rare-earth ion emits, how fast it turns on, how long it glows after the light stops, and which lasers wake it up, alone or in timed pairs. Fire the lasers below and watch each crystal answer only to the light it can use.

Low backgroundInfrared excitation sits away from much of the autofluorescence that complicates visible-excitation assays.
Stable labelsRare-earth crystals are far more resistant to photobleaching than organic dyes, so the code reads the same tomorrow.
Flow cytometryIMS is building high-parameter cytometry around these reporters, with the instrument designed for the materials.
AuthenticationThe same reader logic identifies covert taggants in inks, plastics and coatings.
FIRE
RISE
365 nm800 nm940 nm980 nm1550 nmLASERSalone or gatedEMITTERNd³⁺1064 nm · IRTm³⁺475 nm blueHo³⁺545 nm greenEr³⁺540 + 660 nmEu³⁺612 nm red-orangeTb³⁺545 nm greenPr³⁺488 nm cyan25 µs50 µs100 µs200 µs400 µs800 µs1.6 msLIFETIME τ3658009409801550nmNd³⁺1064 nm · IRTm³⁺475 nmHo³⁺545 nmEr³⁺540 + 660 nmEu³⁺612 nmTb³⁺545 nmPr³⁺488 nm25µs50µs100µs200µs400µs800µs1.6msτ

Tap a crystal to follow it in the detector trace.Hexagon: infrared-excited · Diamond: UV or two-step · Gold outline: electron parked, waiting for the second laser.

Detector trace

Tap any crystal to follow its row.

SIGNALTIME →- - - parked in ¹G₄

Excitation fingerprint

Which emitters answered each laser, and the gated pair.

3658009409801550980→800GATEDNd³⁺Tm³⁺Ho³⁺Er³⁺Eu³⁺Tb³⁺Pr³⁺
READERReady to scan.Five lasers in random order, then a gated pair.
7×7×3
Emitters, lifetimes and rise times: 147 distinguishable crystals.
5+gated
Lasers from 365 nm UV to 1550 nm infrared, fired alone or in timed pairs.
3
Time windows per pulse: the rise, the shift while the laser is still on, and the decay.
2.49 bn
Codes when a tag mixes crystals, up to one lifetime-and-rise choice per emitter: (7 × 3 + 1)⁷ − 1.

Illustration. Ion responses, rise times and lifetimes are simplified for display, infrared emission and lasers are shown in false color, and every clock is slowed thousands of times so the eye can follow it. Not a validated panel.

Yb³⁺ PARTNER²F₇/₂²F₅/₂Pr³⁺ EMITTER³H₄ ground¹G₄³P₀³P₂980hand-off800488 nmwaiting… the gate is open

Energy levels to scale (cm⁻¹). Illustrative timing.

Two lasers, one gate

Climb the ladder in two steps.

Some emitters do not need ultraviolet at all. In Pr³⁺, a 980 nm photon, handed over by a ytterbium partner, lifts an electron to a middle rung, the ¹G₄ level, where it waits. If an 800 nm photon arrives while it is still waiting, the electron is carried over the top to ³P₀ and the crystal glows cyan at 488 nm. Either laser on its own shows nothing.

  • The gate is time. The second laser has to arrive within the middle rung's lifetime. Drag the gap in the scanner above and watch Pr³⁺ go dark when the 800 nm pulse comes too late.
  • A lock with two keys. A reader must know both wavelengths and the timing between them. Copy it with a single laser and the mark stays dark.
  • More codes, same colors. Laser pairs and the delay between them become new dimensions without adding a single emission color.

How the reader figures it out

Light in, time out.

The reader does not just look at a color. It asks each crystal a series of questions with different lasers, alone and in pairs, times every answer, then matches the full response against a library of known materials.

U.S. PATENT 11,435,228 B2 · GRANTED 2022Method and System for Identification of PhosphorsJoshua E. Collins and Howard Y. Bell, Intelligent Material Solutions. Priority July 17, 2018. Read the patent ↗
1Ask with the lasersEach wavelength is held on for milliseconds, typically 10 to 50 ms, in any order, then in gated pairs. Only ions that can use that light answer, so Tb³⁺ and Ho³⁺, both green, are told apart by which laser wakes them.
2Split the answer by colorFiltered avalanche photodiodes each watch one emission band, blocking the lasers themselves, so the reader knows which emitters spoke and how strongly.
3Read the clockHow fast the signal rises, how it shifts while the laser stays on, and how it decays after the laser switches off. Rise and decay are each tuned in the crystal, and the middle window is the heart of the patent.
4Match the libraryThe normalized response is compared with stored fingerprints. A match is called when the differences are not statistically significant (p < 0.05).

Open lab — try it

Ten markers. One stream. No spillover to untangle.

Each cell is labeled with antibodies carrying layered Intelligent Material crystals. As the cells flow single file past four laser spots, every reporter answers only to its own laser, in its own color, on its own clock. A time-gated detector downstream reads the afterglow. Switch the shells off to see what bare crystals can do on their own.

Flow Lab · free and open to allRuns in your browserSimulated cells, illustrative values
10-plexbrightness ×4

STEP 2The reporter panel · each marker a different crystal recipeTap a marker to follow it through the stream.

CD45 × CD3 all events

CD4 × CD8 gated on CD3⁺

CD4 and CD8 reporters need shells: an inert shell to be bright enough, and a Nd³⁺ shell so 808 nm can read CD8.

Populations 0 events

PD-1⁺ of CD8 T: –Ki-67⁺ of tumor: –

LIVE New events ring in as each cell leaves the stream.

Try a challenge.

Two puzzles that color alone cannot solve. Pick one, run the stream, then switch the view until the plot splits into clean populations.

Challenge
Read by

The stream

Histogram

Live plot 0 events

Challenge for illustration. Populations, brightness, lifetimes and noise are modeled, not measured. Lifetimes 100 µs, 400 µs and 1.6 ms are rungs of the ladder in the code space above. The drawing shows one cell in eight; the plot counts them all.

Conventional dyes spillover between channels

Organic dyes have broad, overlapping emission. Every channel leaks into its neighbors, so large panels need a compensation matrix and careful single-stain controls.

Intelligent Material spillover between channels

Narrow rare-earth lines, separate laser spots and a lifetime gate keep each reporter in its own lane. The matrix is close to diagonal.

10
Markers in this demo from four laser spots and one time-gated detector.
4 → 10
Bare cores resolve four of them. Shells add the other six.
40–50
Colors in today's largest spectral cytometry panels, built from dyes that all overlap.
384 M
Core/shell recipes available as distinct reporters, read by laser, color, power and time.
1BrighterAn inert outer shell keeps energy away from the surface and the water around it. Dim reporters become usable markers.
2Orthogonal lasersA Nd³⁺ shell lets 808 nm wake a second set of reporters that 980 nm cannot see. New channels without new colors.
3A clock in every reporterShell thickness tunes lifetime. The gated detector downstream reads the afterglow, so two reporters of the same color still separate.
4The stream is the gateThe 980 and 808 nm spots sit apart along the flow. Spacing divided by flow speed sets the delay for two-step reporters like Pr³⁺.

Simulation for illustration: cell populations, marker levels, reporter responses and noise are modeled, not measured, and the flow is slowed thousands of times so the eye can follow it. The drawing shows one cell in six; the plots count them all. Today's panel sizes: OMIP-069 (40 colors) and OMIP-102 (50 colors), Cytometry Part A.

Where it could go

One code system. Many cytometry questions.

Flow cytometry is an active development program at IMS. These are the directions we are building toward with partners; none is a cleared clinical product today.

PARAMETERS PER TUBEcolor only+ lifetime+ rise timeillustrative
Development area

High-parameter immunophenotyping

Color, lifetime and rise time each add a dimension, so more markers can share one tube and one laser set.

980 nmRARE EVENT FLAGGEDLow background makes one cell in millions easier to callRare cells in a fast stream
Development area

Rare-cell detection

Near-infrared excitation keeps the background dark, which matters most when the event you are looking for is one cell in millions.

CELL THERAPY BAGRELEASE CHECKIdentityengineered cells labeledPurityunwanted cells countedViabilitylive / deadDosecells per bag
Development area

Cell-therapy release testing

Identity, purity, viability and dose for engineered cell products, read with stable labels that do not drift between runs.

BIOREACTORCULTURE HEALTH · AT LINEviable cellsproductstress markerdays
Development area

Bioprocess monitoring

At-line checks on culture health and product for biologics manufacturing, from the bioreactor to the release lab.

code 1code 2code 3code 4Coded beads, one per analyteEach bead carries a crystal code (which test) and capturesits target (how much). Many tests run in one small sample.analyte Aanalyte Banalyte Canalyte DREAD BY FLOWcode
Development area

Coded bead assays

Each bead carries a crystal code for which test it is and captures its target for how much: many measurements from one small sample.

day 0day 3day 7day 14IMS labelorganic dyeLabels that last through division and time
Development area

Long-term cell tracking

Crystals are highly resistant to photobleaching, so a label can follow cells through division and over days of culture.

VISIBLE: tissue glows too980 nm: only labels answer
Development area

Autofluorescent samples

Tissue digests, fixed cells and other bright samples go dark under 980 nm, leaving only the crystal labels.

POOLED LIBRARYDECODEvariant Avariant Bvariant Cvariant Dvariant E
Development area

Pooled screening

Give every variant in a library its own code, run them together, then decode and sort by code.

Looking for rapid tests? The same reporters power quantitative lateral flow →

Build the next panel

Bring us the cells. We'll bring the codes.

IMS designs the crystals, the code library and the reader logic; NovaVera commercializes the platform. Tell us the markers, the instrument and the setting, and we will work backward to the reporters.

Start a cytometry projectNovaVera ↗