Single-cell spectrometry and Giuliano’s Law

Regular readers of this blog are familiar with the crucial importance of signaling molecules and transcription factors in life-related biological processes.  However, traditional mass spectrometry may have difficulty detecting such molecules which are produced in low numbers.  Although mass spectrometry is a very important technique for determining the presence of proteins in cells, the observations it produces produced are averages, often over millions of cells in a culture.  Information related to important subpopulations of cells or what is going on in a single cell is lost.  “Mass spectrometry (MS) has become a preeminent methodology of proteomics since it provides rapid and quantitative identification of protein species with relatively low sample consumption. Yet with the trend toward biological analysis at increasingly smaller scales, ultimately down to the volume of an individual cell, MS with few-to-single molecule resolution will be required(ref).”

A typical laboratory mass spectrometry system is the size of a supermarket food freezer.  Recently-reported research indicates that it may be possible to mass-produce mass spectrometers on microchips, ones that can analyze the proteins in individual cells. “A prototype for a mass spectrometer with single-molecule sensitivity has prospects for single-cell proteomics.   – – With new work from Michael Roukes’s group at the California Institute of Technology, however, this could potentially all change. Roukes and his colleagues recently reported a nanoelectromechanical system (NEMS)-based method that can be used to detect molecular mass with single-molecule sensitivity. — NEMS sensors are nanoscale devices that resonate at frequencies close to the microwave range(ref).”  According to Roukes “We report the first realization of MS based on single-biological-molecule detection with nanoelectromechanical systems (NEMS). NEMS provide unparalleled mass resolution, now sufficient for detection of individual molecular species in real time. However, high sensitivity is only one of several components required for MS. We demonstrate a first complete prototype NEMS-MS system for single-molecule mass spectrometry providing proof-of-principle for this new technique(ref).”“

“The next question is, that’s a lot of molecules that you need to measure one by one, and how the heck are you going to do that?” says Roukes. He envisions an elaborate microfluidics-based front-end separation system, which would distribute the contents of a single cell to a chip consisting of thousands of individual NEMS sensors, each one a tiny mass spectrometer(ref).”  Proof-of-concept has been established but the engineering challenge of building such a device remains. “Roukes is collaborating with researchers at CEA (French Atomic Energy Commission) Leti in Grenoble, to make such chips with thousands or even millions of NEMS sensors. Another challenge they must tackle is pushing the mass resolution to below a single dalton; their current mass resolution is about 1,000 daltons. “This will require us to scale down [the size of] the individual NEMS resonators,” says Roukes(ref).”

This stream of development is another example of what I talked about in my blog post Factors that drive Giuliano’s Law. You may recall that Giuliano’s Law is:

·        Starting now, every seven years will see the emergence of practical age-extension interventions (ones that have a potential of leading to extraordinary longevity) that double the power of the interventions available at the start of the 7 year period.  That is, on an average basis, the practical anti-aging interventions available at the end of a seven-year period will enable twice the number of years of life extension than did the interventions available at the start of the period.  Life extension is measured in years of life expectancy beyond those actuarially predicted for a given population. 

In that post I said “This law is valid for the same reason Moore’s Law for integrated electronics is valid – the law that the number of transistor elements on a chip at a given price point doubles roughly every two years.  This law has held for 40 years and is responsible for the corresponding increase in cost-effectiveness of computers, cell phones and all other electronics.  This law was the result of a strong positive feedback relationship between societal need, market, economic contribution, market vehicles, user applications, marketing channels, changes in user expectations advancement in the relevant basic science, advancement of technology, advancement of manufacturing capability and an entrepreneurial environment.”  And there is yet-another factor I did not mention before, and that is massive government investment in health sciences research.  Advances in basic research technology like spectrometry is one of the key factors driving life extension, a factor that works in close interplay with the other factors mentioned. 

The first computer I worked on, the UDEC at Wayne State University in 1952, was some 60 feet long, weighed several tons and filled a gigantic room under the dome of the old Victorian-design main building.  The computer chip in my Blackberry phone is the size of a large dandruff  flake and is tens of thousands of times more powerful and useful.   And I remember when powerful computers got to be the size of supermarket freezers, in the early 80s.  I wonder if someday we will carry pen or pin-sized mass spectrometers as part of our personalized medicine health monitoring system.