Finding the Source

What is the focus of your research?

I would say that we have two main branches of research. First, we want to speed up analysis, largely by producing portable mass spectrometry (MS) instrumentation. Second, we are developing ‘smart’ automated data processing tools that use algorithms to extract useful information from spectra. We are also working towards developing a ubiquitous ionization source that can be used to detect elemental species, small molecules and large biopolymers; these systems could fragment molecules to obtain structural information and then break it down even further to look at atomic ions. We have actually accomplished this using an ionization source called solution-cathode glow discharge (SCGD).

What advances do you find most exciting?

In terms of instrument development, there’s an emphasis on compact and portable systems, as well as combined systems. We are also seeing the design of analytical instruments for real-world applications, such as the use of MS in medical diagnosis and even in operating theatres; researchers like Livia Eberlin (University of Texas) and R. Graham Cooks (Purdue University) are working directly with surgeons on intra-surgery tumor imaging. Another exciting development is that people are taking commercial, off-the-shelf items like cell phone cameras and developing them into powerful spectroscopic and imaging tools. In fact, Aydogan Ozcan at UCLA is converting cell phone cameras into high-resolution microscopes capable of imaging individual red blood cells.

Are analytical scientists closely involved in these medical applications?

Healthcare professionals and analytical scientists are working closely together to develop the technology, but there is rarely an instrument expert present in the operating theatre. Smart software can help non-expert users operate the instrument and interpret the outcomes, but ideally the operators should have some understanding of the underlying science in case of an algorithm failure or other malfunction.

Pick of the Papers

We asked Jacob to list three recent publications that have caught his eye…

Ultrasonic sculpting of virtual optical waveguides in tissue - M Chamanzar et al., Nat Comm, 10, 92 (2019).DOI: 10.1038/s41467-018-07856-w

What? - Using ultrasound waves to improve the retrieval of light by optical imaging tools in biological contexts – in this case, in mouse brain tissue.

Why?  - The imaging of biological events in vivo (in the body) has invaluable applications such as the simulation of brain activity. Yet, current approaches cannot maintain high spatial resolution when studying deep tissue due to light absorption, scattering and diffraction. Ways to improve resolution, such as implantable waveguides or optical fibers, may damage the tissue and cause complications; thus, a non-invasive way to steer light into deep tissue is needed.

How?  - Pressure-induced density gradients were established in the tissue using ultrasound waves – these gradients create a refractive index contrast and light is confined in the areas of higher refractive index. The ultrasound waves act as waveguides, guiding light to these areas and acting to counter scattering and diffraction of the incoming beam of light.

Towards in-baggage suspicious object detection using commodity Wi-Fi - C Wang et al., IEEE Conference on Communications and Network Security, 2018.

What? - Applying existing Wi-Fi devices and usual Wi-Fi networks to identify dangerous objects in unopened containers.

Why? - Baggage checking requires specialized instruments and substantial manpower, both of which are expensive. The authors present a method to assess the contents of containers, such as bags, with relatively low cost and without invading the privacy of individuals. The method could be useful in large public spaces, where baggage checks are ineffective, inefficient or both.

How? - The team designed a novel system based on channel state information (CSI) measurements readily available in Wi-Fi devices. The system, comprising a simple Wi-Fi transmitter and receiver, performs both CSI phase adjustment and reconstruction; the CSI measurements were then subjected to a process of material classification and risk estimation, based on shape imaging and volume estimation.

Tip-enhanced Raman imaging of single-stranded DNA with single base resolution - Z He et al., J Am Chem Soc, 141, 753-757 (2019). DOI: 10.1021/jacs.8b11506

What? - Tip-enhanced Raman scattering (TERS) was used to resolve single nucleotide bases (the building blocks of the genetic code) in a single-stranded DNA molecule.

Why? - To demonstrate the subnanometer resolution of TERS – important if it is to fulfil its promise for chemical imaging and sensing at single-molecule scales.

How? - Single-stranded viral DNA was uncoiled and attached to a substrate by its phosphate groups to expose the nucleotide bases. A silver tip was subsequently scanned along the strand at steps of 0.5 nm, comparable to reported distances between stretched DNA bases, to produce a Raman spectrum that could be interpreted based on the expected readouts of individual bases ­– adenine, thymidine, guanine and cytosine – at each step. The accuracy of the resulting sequence was confirmed by comparing it with the known sequence using a string-matching algorithm.

Has artificial intelligence (AI) had a big impact on the field?

Absolutely, and especially on the optical spectroscopy side. The use of and reliance on AI, deep learning and machine learning is expanding. One example is the work of Garth Simpson at Purdue University, whose team has developed a deep learning approach to achieve target levels of spatial resolution in chemical images in a much shorter time. There is also Igor Lednev at the University of Albany-SUNY, who’s using support vector machines and artificial neural networks alongside Raman spectroscopy to diagnose diseases like Alzheimer’s in the early stages. His team is also working towards forensic applications for these techniques, which just emphasizes how widespread the applications of AI could become within spectroscopy.

Is there an area you are particularly passionate about?

The resurgence of atomic spectroscopy is very close to my heart. It’s great to see because this area was thought to have peaked with the success of inductively coupled plasma-MS (ICP-MS), but there remains a need to measure elements and heavy metals. My group is currently working on a portable mass spectrometer for atomic analyses – for now, this is being geared towards nuclear applications by studying uranium isotope ratios. We are close to achieving the detection levels seen with ICP-MS by using a different plasma source on a smaller MS platform; this is the SCGD I mentioned earlier. It has demonstrated detection levels comparable with ICP-MS at the parts-per-quadrillion level and we’re able to get isotope ratio precisions for elements like uranium and lead that are at least as good as with multicollector ICP-MS.

Any other exciting applications in the field right now?

Researchers are starting to tackle longstanding problems, and the use of atomic spectroscopy and MS to detect halogens is a particularly interesting one. Past detection limits with ICP-MS have been very poor in the positive ionization mode and manufacturers don’t make ICP-MS instruments that can record negative ions. Kaveh Jorabchi (Georgetown University) recently developed a very clever method, called PARCI-MS, to detect fluorine. Fluorine-containing molecules are persistent organic pollutants and a global issue – just down the road from my lab at Hoosick Falls (tas.txp.to/Hoosick) there’s been major contamination of water supplies with perfluorooctanoic acid – and the trouble is that there’s no bona fide way to quantify these species. It’s a sure sign of progress that we’re finally ready to start tackling this type of problem.

CSI XLI just took place - what’s your experience of this conference?

The first CSI I went to was in Budapest (2009) and I was immediately impressed, mainly because of the quality of the science and the community that it brought together. CSI hosts scientists involved with many techniques, from Raman to atomic spectroscopy and MS, all of whom attend to share their passion for analytical science. A lot of interesting collaborations have come out of this meeting and it’s also paved the way for strengthening other spectroscopy conferences.

Jacob presented “Simultaneous Elemental and Molecular Detection via Optical and Mass Spectrometries in Search for the Chemical Origins of Life” at CSI XLI, 9-14 June 2019, Mexico City, Mexico