Mass cytometry is a

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...

technique based on

inductively coupled plasma mass spectrometry Inductively coupled plasma mass spectrometry (ICP-MS) is a type of mass spectrometry that uses an inductively coupled plasma to ionize the sample. It atomizes the sample and creates atomic and small polyatomic ions, which are then detected. It is ...

and time of flight mass spectrometry used for the determination of the properties of cells (

cytometry Cytometry is the measurement of number and characteristics of cell (biology), cells. Variables that can be measured by cytometric methods include cell size, cell counting, cell count, cell morphology (shape and structure), cell cycle phase, DNA c ...

). In this approach, antibodies are conjugated with isotopically pure elements, and these antibodies are used to label cellular proteins. Cells are

nebulize In medicine, a nebulizer (American English) or nebuliser (British English) is a drug delivery device used to administer medication in the form of a mist inhaled into the lungs. Nebulizers are commonly used for the treatment of asthma, cystic fibro ...

d and sent through an

argon Argon is a chemical element with the symbol Ar and atomic number 18. It is in group 18 of the periodic table and is a noble gas. Argon is the third-most abundant gas in Earth's atmosphere, at 0.934% (9340 ppmv). It is more than twice as abu ...

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

, which ionizes the metal-conjugated antibodies. The metal signals are then analyzed by a time-of-flight mass spectrometer. The approach overcomes limitations of spectral overlap in

flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...

by utilizing discrete isotopes as a reporter system instead of traditional

fluorophore A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with se ...

s which have broad emission spectra.

Commercialization

Tagging technology and instrument development occurred at the University of Toronto and

DVS Sciences DVS may refer to: * D.V.S*, an American electronic music producer/ guitarist named Derek VanScoten * Developing Virtue Secondary School, Talmage, California, USA Organizations and companies * Descriptive Video Service, a United States produce ...

, Inc.

CyTOF Cytometry by time of flight, or CyTOF, is an application of mass cytometry used to quantify labeled targets on the surface and interior of single cells. CyTOF allows the quantification of multiple cellular components simultaneously using an ICP-MS ...

(cytometry by time of flight) was initially commercialized by DVS Sciences in 2009. In 2014,

Fluidigm Standard BioTools Inc. (formerly Fluidigm) is an American company engaged in the design, manufacture and sale of biological research equipment based on integrated fluidic circuit technology. The company's founders leveraged their semiconductor ...

acquired DVS Sciences to become a reference company in single cell technology. In 2022 Fluidigm received a capitol infusion and changed its name to Standard BioTools. The CyTOF, CyTOF2, Helios (CyTOF3) and CyTOF XT(4th generation) have been commercialized up to now. Fluidigm sells a variety of commonly used metal-antibody conjugates, and an antibody conjugation kit.

Data analysis

Mass cytometry data is recorded in tables that list, for each cell, the signal detected per channel, which is proportional to the number of antibodies tagged with the corresponding channel's isotope bound to that cell. These data are formatted as FCS files, which are compatible with traditional flow cytometry software. Due to the high-dimensional nature of mass cytometry data, novel data analysis tools have been developed as well.

Advantages and disadvantages

Advantages include minimal overlap in metal signals meaning the instrument is theoretically capable of detecting 100 parameters per cell, entire cell signaling networks can be inferred organically without reliance on prior knowledge, and one well-constructed experiment produces large amounts of data. Disadvantages include the practical flow rate is around 500 cells per second versus several thousand in flow cytometry and current reagents available limit cytometer use to around 50 parameters per cell. Additionally, mass cytometry is a destructive method and cells cannot be sorted for further analysis.

Applications

Mass cytometry has research applications in medical fields including

immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...

hematology Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...

, and

oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...

. It has been used in studies of

hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

, cytokine expression, and differential signaling responses.

References

{{Reflist Scientific techniques Mass spectrometry Analytical chemistry Cell biology Clinical pathology Flow cytometry Laboratory techniques