Pet Food with ICP-MS

Optimization of a Soil Particle Content Prediction Model 

Atline Analysis of Commercial Graphene Products 

Making Industrial Raman Spectroscopy Practical

A Brief Survey of Handheld and Portable Instruments 

Instruments Used in Spectroscopy

The New York Section of the Society for Applied Spectroscopy (NYSAS) invites all interested persons to attend their online meeting that is scheduled to be held on January 14, 2021, at 12:00 noon EST.

The meeting includes a talk by senior principal scientist John Wasylyk of BMS and DP Spectroscopy and Training consultant Debbie Peru speaking on "FUNdamentals of Vibrational Spectroscopy."

In this presentation, Wasylyk will provide an overview of basic vibrational spectroscopy and several methods used in the pharmaceutical industry for process optimization and problem solving. Focus will be on the basic theory of three widely applied tools: mid‐infrared, near‐infrared and Raman spectroscopies, and how the key fundamentals of vibrational spectroscopy enhance our process knowledge in the area of research and development. Peru’s presentation will provide a 30,000-foot view of the method development process starting with an overview of the stages of method development and how to create an excellent training set of standards for calibrating your instrument. She will also review the importance of reviewing the integrity of both the X block and Y block of data.

John Wasylyk is a senior principal scientist at BMS and current chair for NYSAS. His background is in natural products chemistry, marine biology, and cryobiology. Over the last 30 years, Wasylyk’s focus has been on traditional analytical chemistry techniques and more recently on non-invasive vibration spectroscopy, including off-line and in-line (PAT) mass spectrometry. His current research focus is the application of vibrational spectroscopy to biopharmaceuticals and its application to downstream processing.

Debbie Peru is a consultant and owner of DP Spectroscopy and Training, LLC, and current secretary for the NYSAS, serving as an officer of this organization for over 20 years. She has extensive industrial experience in applied spectroscopy, data analysis, method development and is a certified facilitator for classroom and virtual training courses. Her career has been highly focused on the area of applied spectroscopy for qualitative and quantitative analysis, quality assurance, problem solving, understanding ingredient interactions, manufacturing cost savings, and product testing.

The meeting will be held virtually over Microsoft Teams. Interested persons can join the meeting from their computer by opening the 

 and click where it says, “Join Microsoft Teams Meeting,” then follow the prompts. For further questions about the meeting, interested persons may contact John Wasylyk at 

Articles

The meeting will take place on Thursday, January 14 from 12:00–1:00 pm EST, hosted by guest speakers John Wasylyk and Debbie Peru.

NYSAS to Host Virtual Meeting on Vibrational Spectroscopy in the Pharmaceutical Industry and Data Integrity 

The Society for Applied Spectroscopy (SAS) and the SAS Atomic Technical Section are pleased to announce the call for submissions to the 2021 SAS Atomic Spectroscopy Student Award. This award will be given to undergraduate and graduate students who have excelled in the area of atomic spectroscopy.

Selected students will be required to present their work as an oral presentation at SciX 2021, which will be held in Providence, Rhode Island, from September 26–October 1.

The 2021 SAS Atomic Spectroscopy Student Award will come with travel assistance greater than $500 and a two-year SAS membership after graduation.

To apply or recommend a student, please submit the following materials:

letter of recommendation from the student’s academic advisor

a scientific abstract for the work he or she will present if selected.

These application documents should be emailed to Derrick Quarles and Ben Manard at 

 no later than March 1, 2021. Late applications will not be accepted. Award winners will be notified in April 2021.

Students that submit an application for the award must be a current SAS member or register at the time of submission. Student memberships can be completed online by clicking 

All questions regarding the 2021 SAS Atomic Spectroscopy Student Award should be directed to SAS at the following email address: 

The Society for Applied Spectroscopy (SAS) and the SAS Atomic Technical Section is currently seeking nominations for the 2021 SAS Atomic Spectroscopy Student Award.

Call for Nominations: 2021 SAS Atomic Spectroscopy Student Award

In March 2020, the United States was in the early stages of the COVID-19 pandemic. We shut the entire country down and ground the economy to a halt in an effort to slow the spread of the virus. Think back to March, and how much uncertainty we were living under.

Nine months later, the FDA approved two COVID-19 vaccines under emergency authorization. Before New Year’s Day, millions of Americans had received the vaccine, including front-line physicians and health care providers and nursing home patients, our most vulnerable citizens.

Nine months. Take a moment to let that sink in.

The mainstream media has crafted a narrative around the COVID-19 pandemic that’s almost entirely negative. For the purpose of ratings, they have described the U.S. response to the pandemic as blundering from one mistake to the next. This narrative is false.

There is another way — a more accurate and underappreciated way — to tell the story of the last nine months. It is a story of heroism, innovation, and precise science, performed under unbelievable pressure.

Let’s not mince words: The United States and the world needs to appreciate the role of the pharmaceutical industry — the researchers, physicians and business leaders — who are rescuing the world from COVID-19. It’s the medical breakthrough of our lifetime.

Instead of dwelling on why many in the media are ignoring this, let’s review some facts.

Since the discovery of COVID-19, here is what scientists have accomplished: They identified a novel virus, unlocked and sequenced its genetic code, created new therapies to save lives, and developed multiple safe and effective vaccines using messenger RNA technology, a technology hopefully applicable to future vaccine development. Margaret Liu, MD, a member of the MJH Life Sciences COVID Coalition, called it a breakthrough for mRNA vaccines.

The United States has two vaccines approved for emergency use, one from Pfizer/BioNTech and another from Moderna, and the AstraZeneca/Oxford vaccine has been approved for emergency use in the UK. In addition, there are 64 vaccines undergoing clinical trials at the moment, including 20 in phase 3 trials. In the United States and around the world, the pharmaceutical industry has answered the call and invested heavily in this effort.

This was the fastest vaccine development program in history, and it’s not even close. David Pride, MD, a microbiologist at the University of California San Diego, estimates that vaccines typically take 10 to 15 years to develop. Until the COVID-19 pandemic, the fastest development timeline was four years, for the mumps vaccine.

Many government systems moved quickly to lessen the burden of onerous regulations and provide funding so that vaccines could be developed quickly but with still rigorous standards. Perhaps it should be a lesson to all of us that regulation/innovation can be calibrated more effectively during “normal” times as industry races to develop new therapies for our world’s other pandemics — cancer, diabetes, heart diseases, and more.

The next step of the process — distribution of the vaccine — will be as challenging as the development phase, if not more so. But again, the pharmaceutical industry is rising to the occasion. Factories around the world are working in overdrive to produce hundreds of millions of vaccine doses.

Already, less than a month after the Pfizer vaccine was approved, more than 15.4 million doses of vaccine have been distributed across the country, and more than 4.6 million people have received their first dose, according to CDC data. Many patients are already receiving their second dose.

While 15.4 million doses are impressive, some expected 20 million doses. But even that is moving the goal line a bit, as six months ago many observers didn’t think we’d get a vaccine until 2021.

Members of our COVID Coalition told us that the holidays slowed the rollout considerably. Nancy Messonnier, MD, a physician with the National Center for Immunization and Respiratory Diseases at the CDC, expects a rapid jump in administered vaccines during these first few days of 2021.

Every day, more people will be vaccinated. After health care workers and our most vulnerable citizens, other frontline workers will be next. Teachers will be vaccinated so our children can return to school. And soon, all Americans will be able to go to their doctor or walk into a CVS or Walgreens and receive the vaccine.

Remember, we did all this in nine months, with the help, dedication and expertise of our pharmaceutical industry heroes. Next time you turn on the TV and see negativity, turn it off and imagine instead where we will be nine months from now.

Mike Hennessy Sr is the founder and chairman of MJH Life Sciences.

The COVID-19 vaccine, and the speed at which it was developed, is the medical breakthrough of our lifetimes.

How Pharmaceutical Innovation is Saving the World

 Emerging Leader in Atomic Spectroscopy Award recognize the achievements and aspirations of a talented young atomic spectroscopist who has made strides early in his or her career toward the advancement of atomic spectroscopy techniques and applications. The winner must be within 10 years of receiving his or her PhD in the year the award is granted.

The award will be given to a researcher who has focused the majority of his or her work in the field of analytical atomic spectroscopy, with direct contributions to inorganic mass spectrometry (MS), optical emission spectroscopy (OES), laser-induced breakdown spectroscopy (LIBS), atomic absorption spectroscopy (AAS), atomic fluorescence spectroscopy (AFS), and/or X-ray techniques through original research on the development or advancement of theory, instrumentation, measurement techniques, or applications.

Information about the person submitting the nomination:

Year PhD was earned and from where (List degree, year, institution, and location):

Important: Candidates must be within 10 years of receiving their PhD in the year the award is granted.

Short summary, in 100–200 words, of the candidate’s achievements or contributions in the field of atomic spectroscopy (more details can follow in the sections below):

Please list the candidate’s five most important pieces of work (such as papers in peer-reviewed journals, issued patents or patent applications, trade secrets, trademarks, commercial products, technical reports written in an industrial community, or other) and explain briefly the significance of each:

Other key contributions to the field of atomic spectroscopy not captured above:

Number of publications and total citations:

Number of oral and poster presentations at scientific conferences:

Service provided to the scientific community, such as volunteer work in scientific societies, work as a journal reviewer, and so on:

To nominate a candidate, please e-mail the following documents to Laura Bush, the editorial director of 

 Please include one seconding letter (letter of support) from a member of the atomic spectroscopy community (this person must be different from the nominator). The nominator may also provide an additional letter of support if desired.

CV or resume of the candidate in in a Word or PDF file

A high-resolution headshot of the nominee in .JPG format

Spectroscopy Emerging Leader in Atomic Spectroscopy: Nomination Form

 Emerging Leader in Molecular Spectroscopy Award recognize the achievements and aspirations of a talented young molecular spectroscopist who has made strides early in his or her career toward the advancement of molecular spectroscopy techniques and applications. The winner must be within 10 years of receiving his or her PhD in the year the award is presented.

The award will be given to a researcher who has focused the majority of his or her work in the field of vibrational or electronic spectroscopy, with direct contributions to Raman, infrared, near-infrared, terahertz, fluorescence, and/or UV-vis spectroscopy through original research on the development or advancement of theory, instrumentation, measurement techniques, or applications.

Important: Candidates must be within 10 years of receiving their PhD in the year the award is 

Short summary, in 100–200 words, of the candidate’s achievements or contributions in the field of vibrational or electronic spectroscopy (more details can follow in the sections below):

Other key contributions to the field of molecular spectroscopy not captured above:

 Please include one seconding letter (letter of support) from a member of the molecular spectroscopy community (this person must be different from the nominator). The nominator may also provide an additional letter of support if desired.

CV or resume of the candidate in in a Word or PDF file.

A high-resolution headshot of the nominee in .jpg format.

Spectroscopy Emerging Leader in Molecular Spectroscopy: Nomination Form

The Emerging Leader in Molecular Spectroscopy Award recognizes the achievements and aspirations of a talented young molecular spectroscopist who has made strides early in his or her career toward the advancement of molecular spectroscopy techniques and applications.

The winner must be within 10 years of receiving his or her PhD in the year the award is presented.


To nominate a candidate, please e-mail the following documents to Laura Bush, the editorial director of 

Year PhD was earned and from where (list degree, year, institution, and location). 

Please list the candidate’s five most important pieces of work (such as papers in peer-reviewed journals, issued patents or patent applications, trade secrets, trademarks, commercial products, technical reports written for an industrial community, or other) and explain briefly the significance of each.

Other key contributions to the field of molecular spectroscopy not captured above

Number of publications and total citations

Number of oral and poster presentations at scientific conferences

Service provided to the scientific community, such as volunteer work in scientific societies, work as a journal reviewer, and so on

Please include one seconding letter of support from a member of the molecular spectroscopy community (this person must be different from the nominator). The nominator may also provide an additional letter of support if desired.

Please provide a current resume or CV of the candidate in a Word or PDF file.

Include a high-resolution headshot of the nominee in a .JPG format

The nomination form can also be downloaded from this 

Submission Deadline for the 2021 award: February 22, 2021

Questions about the submission process should be directed to Laura Bush, the editorial director of 

Spectroscopy magazine is seeking nominations for the Emerging Leader in Molecular Spectroscopy Award.

Call for Nominations: 2021 Emerging Leader in Molecular Spectroscopy Award

The Emerging Leader in Atomic Spectroscopy Award recognizes the achievements and aspirations of a talented young atomic spectroscopist who has made strides early in his or her career toward the advancement of atomic spectroscopy techniques and applications.

The winner must be within 10 years of receiving his or her PhD in the year the award is granted.

Using the downloadable form available on this page, please provide the following information about the person you are nominating:

Short summary, in 100–200 words, of the candidate’s achievements or contributions (more details can follow in the sections below).

Please list the candidate’s five most important pieces of work (such as papers in peer-reviewed journals, technical reports written for an industrial community, or other) and explain briefly the significance of each.

Other key contributions to the field of atomic spectroscopy not captured above

Please include one seconding letter (letter of support) from a member of the atomic spectroscopy community (this person must be different from the nominator). The nominator may also provide an additional letter of support if desired.

Include a high-resolution headshot of the nominee in a .jpg format

The nomination form can be downloaded from this 

Spectroscopy magazine is seeking nominations for the Emerging Leader in Atomic Spectroscopy Award.


Call for Nominations: Emerging Leader in Atomic Spectroscopy Award

R.C. McDowall is the principle of McDowall Consulting and director of R.D. McDowall Limited, and "Questions of Quality" column editor for LCGC Europe, Spectroscopy's sister magazine.

The need to calibrate and qualify analytical instruments and systems is well recognized in laboratories. However, calibrating and qualifying analytical instruments and systems are seen as discrete tasks. There is an increasing regulatory expectation that a risk-based life cycle approach is necessary to ensure “fitness for purpose” as part of an analytical procedure. The calibration and qualification lifecycle of analytical instruments and systems is a journey and not a sequence of disconnected events.

This article describes the principal stages of the lifecycle in both GXP or ISO/IEC 17025 laboratories that ensure that any analytical instrument and system is “fit for its intended use” as part of an analytical procedure, whether that is calibration or qualification. However, the tasks typically associated with these stages are often seen as discrete activities, but they should be integrated to form a continuum. In other words, the calibration and qualification lifecycle of analytical instruments and systems is a continuous journey, not a sequence of disconnected events. It is timely to consider a lifecycle approach because the United States Pharmacopoeia (USP) proposed a new General Chapter <1220> in September 2020 for analytical procedure lifecycle management (APLM) (1). There are no novel elements in this approach, but there is a structured process linking these activities that is described here.

Our starting point is the U.S. Good Manufacturing Practice (GMP) regulation for equipment design, size, and location in 21 

Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (2,3).

What does the phrase “intended use” mean and how should “fitness for intended use or purpose” be demonstrated in a regulated laboratory? Using our analytical instruments for analysis, we reviewed the high level process flow for the analytical procedure lifecycle from the proposed USP <1220> shown in Figure 1 (1). Notice that the key part of the process is stage 1 (Procedure Design, Development and Understanding). Method development is critical to the success of the whole process, and the draft USP <1220> covers an activity that the current International Council on Harmonization (ICH) Q2(R1) does not (4). Consequently, analysts developing methods must ensure that their analytical instruments are qualified and calibrated correctly and that the analytical systems are validated to ensure the smooth development and transfer of methods to the next stage of the lifecycle, which is called procedure performance qualification (PPQ). Qualification and calibration of analytical instruments is particularly important when analytical procedures are developed and validated in Research and Development (R&D) and later transferred to quality control laboratories.

Figure 1 shows that analytical procedure validation is no longer a discrete activity but a journey. As part of that journey, the first aspect of stage 2 PPQ requires qualification and calibration of instruments and systems as a prerequisite.

Analytical Process: Where Does Qualification and Calibration Fit? 

The analytical process, conducted within a pharmaceutical quality management system, provides reliable, traceable, and reportable values that are secure. The basic analytical process is shown in Figure 2 together with the relationship to stage 2 of the APLM highlighted in blue.

If we cannot demonstrate “fitness for purpose” of our instruments and systems, then outputs from our analytical process are unreliable. The current regulatory focus on data integrity and data governance requires us to put in place technical and procedure controls throughout the analytical process to ensure that data and records are trustworthy and reliable, and that quality decisions can be made in confidence.

The data governance and data integrity requirements and controls for a proposed analytical instrument and system (AIS) lifecycle that is defensible from a regulatory and technical perspective in Figure 2 can be mapped to the Foundation and Level 1 of a Data Integrity Model (5-8), shown in Figure S1, online. The Foundation ensures the right culture, ethos, and training for data governance and Level 1 ensures that instruments and computerized systems are calibrated, qualified and where appropriate validated for their intended use.

Analytical Instrument and System Lifecycle

The overall purpose of the AIS lifecycle is to demonstrate that not only is the instrument or system calibrated or qualified, but that any software is suitably validated and is operating in a controlled state. It is only then may we claim that the instrument or system is “fit for intended purpose” so that metrological data integrity is ensured. This article focuses on level 1 in this model concerning metrological integrity. The AIS lifecycle is shown in Figure 3. Data quality is only ensured if all components of data integrity and data governance are in place.

The levels of the AIS, with a specific focus on analytical instruments and systems, are presented at the bottom of Figure 3. Levels 1 and 2 are broken down into four elements each to provide metrological and procedural integrity, respectively. Levels 1 and 2 also overlay the culture and ethos of the foundation level. The quality oversight and some of the foundation level elements of the model are combined under data governance. Together these provide the essential requirements for the right reportable result at level 3 with associated data quality to ensure the correct decision is made.

The top portion of Figure 3 is based on the requirements of USP <1058>, analytical instrument qualification (9)that requires the following:

1) A laboratory user requirements specification (URS) to select the right instrument for the job (design qualification)

2) Following purchase of the instrument, a supplier IQ/OQ is per- formed to demonstrate that the requirements in the laboratory URS have been met. If this is not the case, the laboratory needs to conduct supplementary qualification tests to match the operating ranges specified.

3) Performance qualification (PQ) tests to demonstrate that the laboratory specifications are being met during operation of the instrument must be devised along with a plan for requalification of the instrument both after repair and maintenance but also periodically. 

4) The PQ test performance should be trended to detect any changes as well as maintaining deviation management and change control to demonstrate that the instrument is in a state of control.

The authors have published a risk assessment to help classify analytical instruments and systems into the USP <1058> groups and subtypes and suggest the extent of computerized system validation to be undertaken (10). Combining all the activities shown in Figure 3 ensures that analytical instruments and systems generate data and reportable results with appropriate integrity and quality.

Recently in Pharmacopoeial Forum, a stimulus to the revision process article was published discussing a lifecycle approach to both calibration and qualification (11). However, before we discuss this article, we need to consider the applicable FDA GMP regulations, by going back to the future.

Since the promulgation of the GMP regulations in 1978, approaches to ensuring that analytical instruments are “fit for intended use” have changed along with the terminology. Analytical instruments have changed and software, either in the form of firmware or a separate data system, now comprises a major component of modern analytical instrumentation. However, the wording of the regulations has not changed but the interpretation of them has. In 21 

 211.160(b) there are requirements that any laboratory control mechanisms must be scientifically sound and in 211.160(b)(4) we have the following requirement for calibration (3):

The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used.

The records for such calibrations are defined in 211.194 (d) (3):

Complete records shall be maintained of the periodic calibration of laboratory instruments, apparatus, gauges, and recording devices required by 211.160(b)(4).

The problem is that the U.S. GMP regulations only mention calibration and therefore citations in 483 observations and warning letters will only cite deficiencies in instrument calibration when a qualification lapse could be the cause of the noncompliance, resulting in potential confusion. However, as our understanding of how to demonstrate fitness for intended use has evolved, so has the terminology.

The terms used within this section are one of the sources of great confusion between laboratories. For example, 

 can sometimes be used as a general “descriptive label” or have a specific meaning within the context of use. In addition to calibration, we now have the terms 

 also in common use. USP general chapter <1058> on analytical instrument qualification (9) provides an integrated approach to qualification of the analytical instrument and validation of the software. This general chapter mentions the terms calibration, qualification, verification, and validation. What do these terms mean? Are they linked? And where are we going in the future? All organizations, including regulatory authorities, need a technical glossary. There is no technical glossary that ensures a consistent meaning and use of terms throughout the pharmacopeia and other regulatory documents.

It is generally accepted that calibration forms part of the overall qualification process of an instrument or system. Calibration is all about metrology. Calibration is that part of qualification relating to measurement integrity of the ordinate response and abscissa functions, that is, all measurements from the instrument or system are within defined acceptance limits of a true or certified value.

The foundation for assurance of metrological “fitness for purpose” lies with the correct use of either a certified reference material (CRM) or a reference standard (RS). In the pharmacopeia, calibration is a comparison between a known or accepted value of a CRM or RS with its measured value on a specific laboratory analytical instrument or system being used for a pharmacopeial purpose the difference between these two values is compared with an acceptance criterion that may be an acceptable range or tolerance interval. For example, the measured value of a certified standard value of a wavelength standard must lie within the acceptance criteria of ±2 nm over the spectral range 200 to 400 nm. For some analytical instruments, calibration may all that is required (9).

Qualification is about overall “fitness for purpose” of an instrument or system, not only about good numbers. Hence the pharmacopeias require qualified instruments and systems. 

 <1058> is the only pharmacopoeial general chapter to describe the overall process of analytical instrument qualification (9).

 relates to the “fitness for purpose” of analytical procedures as required by the General Chapter on Verification of Analytical Procedures <1226> (12). However, verification is also used in the American National Standards Institute (ANSI) for software to refer to demonstrating that each individual step is mathematically or procedurally correct. GAMP 5 describes the testing phases of a computerized system lifecycle to demonstrate meeting user specifications (13). Therefore, some aspects of modular calibration (see later section) may be regarded as a verification process. The current version of 

 <1058> on analytical instrument qualification (AIQ) does not use 

Currently, validation relates either to the establishment of analytical procedures as required by General Chapter <1225>, Validation of Analytical Procedures (14) or particularly in General Chapter <1058>, Analytical Instrument Qualification for “fitness for purpose” (9). For example, in the “Instrument Control, Acquisition and Processing Software” section of <1058>, it states:

At the user site, integrated qualification of the instrument, in conjunction with validation of the software, involves the entire system. This is more efficient than separating instrument qualification from validation of the software (9).

However, there is a diversity of definitions for calibration, qualification, verification, and validation within the USP General Chapters that need to be harmonized to assist understanding and prevent user confusion. This is particularly true for the differentiation of holistic and modular calibration standards and the expression of acceptance criteria for establishing “fitness for purpose” (15,16).

The perennial question of “who does what and when” is answered in the lifecycle approach to calibration shown in Figure 4. The solid lines denote the primary process flows for establishing and confirming “fitness for purpose.” Dotted or dashed lines indicate either feedback loops triggered by data generated during the ongoing performance phase or, in the case of the URS, supported by the vendor.

The generic process of calibration and qualification should be designed to allow confirmation of “fitness for purpose” at all stages in the lifecycle including assurance of preventative maintenance and change control.

Users need to define their own control strategy to specify ongoing “fitness for purpose” by establishing the frequency of calibration, standards and acceptance criteria that will be employed and trend analysis of the ongoing performance data from the instrument.

One important aspect of the calibration and qualification lifecycle is the presence of change control feedback loops as part of the lifecycle. For example, if the qualified operational wavelength range for a UV spectrometer was originally 240 to 600 nm and the requirement is to extend this to 210 to 600 nm, then a new qualification standard is required to confirm “fitness for purpose” (17–19). In addition, the laboratory URS needs to be reviewed to ensure that the instrument was correctly specified originally to allow the revision of operational range.

Do You Specify Exactly What You Need the Instrument or System to Do?

 <1058> (9) is defined in a user specification. These are laboratory requirements for any analytical instrument with scientifically sound acceptance criteria. This does not mean simply copying the supplier’s specification, as discussed in an earlier column (18) but defining what is actually required. For example, if a UV-vis spectrometer has a supplier’s wavelength specification between 190 and 800 nm, what do you actually use? For example, if you only require measurement between 210 and 300 nm, then this should be your operating range. The requirement for wavelength accuracy is contained in 

 <857> (20) and this should be quoted in the specification document for the instrument. Testing wavelength accuracy using a CRM (for example, a holmium perchlorate solution or a glass filter) should demonstrate that this user requirement is met and that the instrument performs within scientifically sound acceptance criteria. Similar approaches need to be undertaken for the other technical requirements for the spectrometer.

Best Practices for Instrument Calibration

The best practice is to use the most stable artifact with the smallest uncertainty budget. For example, for routine monitoring of UV-vis and near infrared spectrometers, solid or liquid filters traceable to a national measurement institution (NMI), for both wavelength and absorbance accuracy qualification provide the most reliable option for the user.

For example, Figure 5 shows an overview of available standards for UV-vis-NIR over the overall spectral range available from one manufacturer. For example, to cover an operational wavelength range of 200 to 795 nm, two references would be required.

The calibration and qualification of analytical systems is a journey, not an event.

Are You Ready for a Life Cycle Approach for Analytical Instruments and Systems?

David Tuschel is a Raman applications manager at Horiba Scientific in Edison, New Jersey, where he works with Fran Adar. David is sharing authorship of the "Molecular Spectroscopy Workbench" column with Fran.

Group theory in conjunction with Raman polarization selection rules may be applied to the study and characterization of crystalline materials. The Polarization–Orientation (P-O) Raman method employs this relationship, and is useful for the identification of a material’s crystal class, orientation, degree of disorder, and determination of the symmetry species to which the Raman bands in a spectrum belong. Furthermore, it can be used to distinguish allotropes and polymorphs, differentiate single from polycrystalline materials, and determine whether materials at different locations in a fabricated device are crystallographically aligned. We discuss the theory and sensitivity of P-O Raman spectroscopy in the backscattering mode applied to crystals for which the nonzero Raman polarizability tensor elements of symmetry species are neither necessarily equal nor proportional. We demonstrate the effects of Raman polarizability tensor relative values and crystal orientation by calculating P-O Raman diagrams for the A and E symmetry species of the trigonal 

Raman crystallography is the application of group theory and Raman polarization selection rules to the study and characterization of crystalline materials. Characterizing crystalline materials by Raman spectroscopy is a good alternative when sample size or structure precludes one from doing so by X-ray diffraction. Where sample morphology or spatial variation of chemical composition or crystalline structure is on a scale that precludes or makes impractical the use of X-ray diffraction, polarized micro-Raman spectroscopy can often obtain crystallographic information. Applications of applied polarized Raman spectroscopy include characterization of minerals, integrated electronic and electro-optic devices, microelectromechanical systems (MEMS), and organic electronic devices including photovoltaics and organic light emitting diodes (OLEDs).

Most spectroscopists are familiar with Raman spectroscopy as a method of chemical analysis because of its sensitivity to the masses of a compound’s constituent atoms and their bond lengths and force constants. In addition, Raman spectroscopy can also be used for the characterization of the atomic structure of solids because Raman scattering depends on the polarization and direction of the incident light, the crystal symmetry and orientation of the solid sample, and the direction and polarization of the collected scattered light. Micro-Raman spectroscopic methods for determining local crystal orientation in silicon have been developed which take advantage of these properties (1,2). Raman crystallography can be applied to many materials, and the interested reader can find very elegant polarized Raman spectroscopic applications to characterize GaN (3), sapphire (4), and zirconia (5).

Polarization–Orientation Raman Spectroscopy

We discussed one method of Raman crystallography called Polarization–Orientation (P-O) Raman spectroscopy in a prior “Molecular Spectroscopy Workbench” installment (6). The P-O Raman method is useful for the identification of a material’s crystal class, orientation, degree of disorder, and determination of the symmetry species to which the Raman bands in a spectrum belong. To understand how this relationship can be applied to the characterization of crystals, we begin by considering the most fundamental expressions related to Raman scattering:

where α is the Raman polarizability tensor representing the vibrational modulation of the polarizability, 

 is the incident electric field vector, and 

 is the time varying dipole moment (also a vector) induced by the interaction of the incident electric field with the vibrationally modulated polarizability of the chemical bond. The Raman polarizability tensor is fixed relative to the positions of the atoms and the directions of the chemical bonds between them. Therefore, for a crystal fixed in space the relationship described by equations 1 and 2 is dependent upon the crystal symmetry and orientation of the sample relative to the direction and polarization of the incident and collected light. This relationship constitutes that part of the expression for Raman scattering intensity of interest to us in equation 3:

 is the intensity of the incident light, 

 is a factor incorporating the dependence on the frequency of the incident light, 

, the polarization of the incident light, and 

 and Ω are the polarization and solid angle, respectively, at which scattered light is collected. The significance of this expression for work with crystals is that Raman scattering intensity is proportional to the square of the dot product of the incident electric field vector, Raman polarizability tensor, and scattering vector.

The theory and general application of P-O Raman spectroscopy in the backscattering mode is based on the interdependence of incident electric field, Raman polarizability tensor and scattering vector. Most important is that the forms (whether elements are zero or nonzero) of the Raman polarizability tensors for crystals are dictated by the symmetry species of the crystal class to which the material belongs. The absolute magnitude of the tensor elements will be dictated by the specific chemical bonds between the atoms. However, whether a Raman tensor element is zero or nonzero is entirely dictated by the crystal symmetry. There are 32 crystal classes and the forms of the Raman polarizability tensors have been determined for all of them and tabulated in various publications (7–9).

In that previous introduction to P-O Raman spectroscopy, we demonstrated good agreement between the experimentally obtained results from single crystal Si and the calculated predictions for several crystallographic faces (6). The most common crystalline form of Si is cubic with two atoms in the primitive cell and belonging to crystal class 

. The first order optical phonon at 520 cm

 is triply degenerate and there are three 

 Raman polarizability tensors of the form:

where the letter d indicates a nonzero value. An experimental arrangement can be envisioned in which the laser beam is incident along the 

-axis with respect to the laboratory reference frame. This arrangement corresponds to the Raman microscope backscattering configuration. A cubic single crystal Si chip is positioned such that its crystallographic XY-plane is coplanar with the laboratory XY-plane. Backscattered light is collected in two configurations, with the analyzer either parallel or perpendicular to the polarization of the incident laser light. Raman scattering strengths (normalized) equal to the square of the dot product in equation 3 have been calculated for the analyzer parallel and perpendicular to the incident polarization as the crystal is rotated in the XY-plane. The calculated P-O diagram for Raman backscattering signal strength of the first order optical phonon at 520 cm

from the XY-face of cubic Si is shown in Figure 1.

The parallel and perpendicular responses are sinusoidal functions 45° out of phase, and, of course, because of the cubic symmetry the response is the same for the XZ- and YZ-faces. However, if the crystal is oriented out of these planes, one begins to see the effect of orientation on the P-O Raman plots. The method used to transform the Raman polarizability tensors from one crystal orientation to another is the transformation through Euler’s angles (10). The interested reader can refer to our previous publication to compare the P-O Raman results for the (100), (110) and (111) faces of cubic Si (6).

We have performed P-O Raman calculations for many other Si crystal orientations and have found the method to be very sensitive to crystal orientation. In fact, this sensitivity will be true for crystals of all symmetry classes because the P-O Raman diagrams depend only on the forms of the Raman polarizability tensors. Crystals of symmetry lower than that of the cubic system can have Raman polarizability tensors in which the nonzero elements are not equal, and in those cases, the P-O diagram will be affected by the relative magnitudes of the tensor elements. In fact, comparing calculated P-O Raman diagrams to the experimentally obtained P-O plots allows one to infer relative Raman scattering cross-sections of vibrational modes from crystals. The form or pattern of P-O Raman diagrams are dependent upon crystal symmetry and the relative magnitudes of the nonzero tensor elements, which depend upon the specific elemental, compositional, or molecular identity of the crystal. That is what makes the P-O Raman method a useful basis for Raman crystallography.

One can immediately recognize the application of this method for the characterization of crystal structure and orientation in either naturally occurring materials or fabricated devices. The P-O Raman method is complementary to X-ray diffraction, and should be considered when X-ray analysis is not practical or possible. P-O Raman spectroscopy may be used to identify vibrational modes, distinguish allotropes and polymorphs, distinguish single from polycrystalline materials, and determine orientation of the crystal and degree of disorder. Furthermore, one can determine whether materials at different locations in a fabricated device are crystallographically aligned based upon the phases of the experimentally obtained P-O Raman diagrams.

The nonzero elements of the triply degenerate 

 crystal class are all equal. Therefore, only the crystal orientation can affect the P-O Raman diagram for that symmetry species. The cubic system is a special case of high symmetry and all of the nonzero tensor elements of the various symmetry species of the cubic classes are either equal or proportional to each other. That is not the case for the other 27 crystal classes that do not belong to the cubic system.

Here, we discuss the theory and more general application of P-O Raman spectroscopy in the backscattering mode applied to crystals for which the nonzero Raman tensor elements of symmetry species are neither equal nor proportional. We demonstrate the effects of Raman tensor relative values and crystal orientation by calculating P-O Raman diagrams for the 

 crystal classes. The Raman tensors of these symmetry species are shown in equation 5. The 

 symmetry species is doubly degenerate and so there are two Raman polarizability matrices associated with that species.

 symmetry species in equation 5 and note that only the diagonal tensor elements are nonzero. Furthermore, α

, and, as we will see, the relative magnitudes of the tensor elements will affect the PO Raman diagram depending upon the sample’s crystal orientation. The P-O Raman experimental arrangement can be envisioned in which the laser beam is directed along the 

-axis, with respect to the sample’s crystallographic axes and at a crystal rotational angle of 0°. The XY-face of the trigonal 

 crystal is positioned coplanar with the XY-plane of the laboratory frame, and backscattered light is collected along the z-axis. Raman scattering strengths for α

 = 10 have been calculated for the analyzer parallel and perpendicular to the incident polarization as the crystal is rotated in the XY-plane. The calculated P-O diagram for Raman backscattering signal strength from the XY-face of the A symmetry species of a trigonal 

 crystal is shown in Figure 2. The P-O Raman responses for both parallel and perpendicular configurations are invariant with crystal orientation. The parallel Raman signal is allowed and always equal to the squared α

 values of 1, whereas the perpendicular response is forbidden, yielding a Raman signal of zero. Mathematically, the reason for these responses is that both diagonal tensor elements within the XY-plane of rotation are equal to 1, whereas α

 is perpendicular to the plane of rotation, and does not contribute to the signal in the backscattering configuration. In this experimental arrangement the specific value of α

, which in this example is 10, has no effect on the P-O Raman diagram.

Now, envision rotating the crystal 90° such that the laser is incident upon the YZ-face and is polarized along the 

-axis when the crystal rotation angle is at 0°. Relative Raman scattering strengths have been calculated for the analyzer parallel and perpendicular to the incident polarization as the crystal is rotated in the YZ-plane. In this configuration, the relative magnitudes of the α

 values directly affect the P-O Raman diagram, because the crystal rotation is in the YZ-plane and the dot product of equation 3 varies with crystal orientation. The calculated P-O diagrams for Raman backscattering signal strength from the YZ-face of the A symmetry species of a trigonal 

 values are shown in Figure 3. Note that the P-O Raman diagrams of the YZ- and XZ-faces are identical because the α

 values for the P-O Raman diagrams in Figure 3 are 0.01, 0.25, 0.5, and 0.75, all less than 1, the value we designated for α

. The Raman signal strengths for parallel and perpendicular configurations vary with crystal orientation, with the perpendicular response varying at twice the frequency as that of the parallel configuration. The P-O Raman diagrams of the A symmetry species obtained from the YZ-face are entirely different from that of the XY-plane, which was invariant with crystal angle. That is because the contributing Raman tensor elements are not equal when probing the YZ-face, whereas those contributing in the XY-plane are equal. The Raman signal reaches a maximum in the parallel configuration at 90° and 270°, whereas in the perpendicular configuration the Raman signal peaks at 45°, 135°, 225°, and 315°. The crystal angle separation between the maxima are 180° and 90° for the parallel and perpendicular polarization configurations, respectively. The P-O Raman response maxima remain at the same angles of crystal orientation for all α

. However, there are two noticeable variations in the P-O Raman diagrams, as the α

 values are changed relative to that of α

. The valley at 180° becomes less broad and more rounded with increasing α

 values. Also, the amplitudes of the parallel and perpendicular responses decrease, and the two functions separate, as the α

. These calculated P-O Raman diagrams demonstrate that experimentally obtained P-O Raman responses can be used to identify the crystalline face, assign the symmetry species of a particular Raman band, and determine the relative values of the α

Raman spectroscopy is extremely useful for characterizing crystalline materials.

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