Profile

L. J. Kricka

Professor of Pathology and Laboratory Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia

Larry Kricka was born in 1947, in Karlovy Vary, a spa town in Czechoslovakia (now the Czech Republic). His family moved to England the following year and settled in Birmingham. He now lives on Philadelphia′s historic Main Line, in Devon, Pennsylvania with his wife Barbara. Their three children have ‘flown the nest’.

1965: B.A. (Hons, I) York University, York, England (Chemistry)

1968: D.Phil. York University, York, England (Chemistry, with Dr. John Vernon)

1971: Research Assistant, Liverpool University, Liverpool, England (with Prof. Tony Ledwith)

1973: Lecturer, Clinical Chemistry, Birmingham University, Birmingham, England

1980: Senior Lecturer, Clinical Chemistry, Birmingham University, Birmingham, England

1981: Honorary Consulting Officer in Clinical Chemistry, Central Birmingham Health District, Birmingham, England

1981: Medical Research Council Travelling Fellow, University of California at San Diego, San Diego, CA, USA (in laboratory of Prof. Marlene DeLuca and Prof. Bill McElroy)

1981: Society of Analytical Chemistry Silver Medal (Royal Society of Chemistry) (1981)

1983: Fellow, Royal Society of Chemistry

1987: Reader in Clinical Chemistry, Birmingham University, Birmingham, England

1987 to date: Professor, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA

1987 to date: Director, General Chemistry Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA

1991: Fellow, Royal College of Pathologists

2000: Fellow, National Academy of Clinical Biochemistry

2001: President of the American Association for Clinical Chemistry

2002: Distinguished Visiting Scholar, Christ′s College, Cambridge, England

Research

I have always been interested in chemistry, and as a boy assembled a large, and in hindsight, probably dangerous, chemistry set. My thesis work with Dr. John Vernon at York University focused on synthetic and mechanistic problems in heterocyclic chemistry (isoindoles and 7-azabicyclo[2.2.1.]hepta-2,5-dienes). Subsequent postdoctoral studies at Liverpool in Prof. Ledwith’s laboratory were directed towards cation radical chemistry, and the synthesis of heterocyclic monomers as part of a program to produce slow-release drugs. This sparked my interest in the biological applications of chemistry and led me to my first faculty position as a Lecturer in Clinical Chemistry at the University of Birmingham. The Clinical Chemistry Department was based in the Wolfson Research Laboratories and this multidisciplinary environment did much to shape my subsequent career. Prof. Tom Whitehead’s Wolfson Research Laboratories was a unique and innovative centre that combined academic and routine clinical chemistry, and a remit to undertake research and development in clinical laboratory science and to promote innovations that could be taken up by industry. At the Wolfson, I began my work on various high-resolution analytical techniques, such as two-dimensional protein electrophoresis, and the applications of bioluminescence and chemiluminescence to clinical analysis, and learned that ‘patent or perish’ is just as important as ‘publish or perish’. My interest in bioluminescence and chemiluminescence stemmed from the high sensitivity possible with these reactions, and their potential application as labels or detection reactions in immunoassay and nucleic acid probe assays. The most important commercial outcome of my work during this time (in collaboration with Prof. Tom Whitehead, Dr. Gary Thorpe, Dr. Richard Stott and Dr. Tim Carter) was the ‘enhanced chemiluminescence assay’ for horseradish peroxidase labels. This was patented and commercialized by several companies. As part of the commercialization of this technology, the Wolfson team engaged in extensive technology transfer activities in collaboration with the British Technology Group. Subsequently, the Wolfson team has been recognized with several prizes and awards for their role in the discovery and development of this technology [British Technology Group Academic Enterprise Competition Award (1985), Department of Trade and Industry, Industry Year Award for Technology Transfer (1986), Prince of Wales Award for Innovation and Production (1989), Queens Award for Technological Achievement (1990), Rank Prize for Opto-Electronics (1991)].

In 1981, I was fortunate enough to be awarded an MRC travelling fellowship. I chose to spend the year at the University of Southern California, in San Diego, in order to work with Prof. Marlene DeLuca and Prof. Bill McElroy, on analytical applications of bioluminescence. During this time, I studied the analytical uses of co-immobilized firefly and marine bacterial luciferases. A chance meeting with Prof. Aldo Roda (also on sabbatical from the University of Bologna, Italy), led to the successful development of an automated bioluminescent serum bile acid assay based on mixtures of enzymes co-immobilized on Sepharose beads. In 1986, my ongoing interest in bioluminescence and chemiluminescence eventually led me to found a journal devoted to the basic and applied aspects of these phenomena (Journal of Bioluminescence and Chemiluminescence) and later to expand its scope to cover all types of light emitting reactions, and rename it the Journal of Luminescence.

A major turning point in my career was the decision to move to the United States to join the Department of Pathology and Laboratory Medicine at the University of Pennsylvania (PENN) in 1987. My move to PENN provided new challenges, new horizons, and an opportunity to initiate new collaborative research programs.

At PENN, I have continued my work on enhanced chemiluminescence, and developed new interests in human anti-animal antibodies. These are circulating antibodies that if not recognized, can have a devastating effect on certain types of immunoassays (i.e., false positive results leading to possible misdiagnosis). My major research activity has been the investigation and development of microchip-based analyzers, as a collaborative venture with Prof. Peter Wilding, Prof. Jay Zemel, Prof. Paolo Fortina and Prof. Jing Cheng (instigator of the soon to be completed National Engineering Research Center for Beijing Biochip Technology). The work has ranged across many potential routine clinical applications for small silicon-glass and plastic microchip-based analytical devices. It has included microchips for the polymerase chain reaction, ligase chain reaction, immunoassay, cell isolation and separation, semen testing, and in vitro fertilization. When we began this work in the latter part of the 1980s, it proved difficult to obtain funding for microchip work—basic science funding agencies thought the work too applied and directed us to agencies more concerned with applied research, and they in turn considered the work too basic, and redirected us to the basic science funding agencies. The escape from this Catch 22 situation was to seek venture capital funding, and this set the stage for the formation of a start-up company (eventually merged with Caliper Technologies Corporation), and what has ultimately matured into an extensive patent portfolio on microchips and microchip applications. Current work of the group is directed towards the development of a small analytical platform that houses a series of microchips designed to automate all of the steps in a genetic test starting from a whole blood sample. The goal is to realize a micro-total analytical system or a lab-on-a-chip. Microminiaturization offers some unique capabilities that may turn out to be a perfect match for the complex analytical problem of simplifying a multi-step genetic test. However, this is not a simple process, and there are many challenges to implementing a microchip-based assay including the human interface with the microchip and adverse surface chemistry issues.

In 2002, I returned to England for a 6 month sabbatical as Distinguished Visiting Scholar at Christ’s College in Cambridge. During this time I investigated aspects of nanotechnology research in Europe, continued my long-standing editorial collaboration on the International Bioluminescence and Chemiluminescence Symposium proceedings series, with Dr. Philip Stanley, and completed a book for the AACC Press on ‘Analytical Microchips’.

Since returning from Cambridge I have resumed my work on microminiaturization and have continued to contribute to more global interests in microminiaturization as chair of the Working Group on Microminiaturization of the International Federation of Clinical Chemistry (IFCC), a member of the International Union of Pure and Applied Chemistry (IUPAC) Task Force on Microtechnology and Nanotechnology, and as a member of the National Committee for Clinical Laboratory Standards (NCCLS) subcommittee on Diagnostic Nucleic Acid Arrays.

Conclusion

My research career has been very broadly based. A common thread has been my interest in the possible applications of my research and timely invention disclosures and patenting to protect ideas so that they are in a condition for exploitation. The microchip area has proved to be particularly fertile, and many groups have developed novel and useful microchips that may eventually be common everyday devices in analytical laboratories worldwide. In the meantime, the future of my discipline, the clinical laboratory sciences, is difficult to predict. It seems certain that initially microtechnology, and at some later period, nanotechnology will assume an important role in the techniques used to analyze biological specimens as an aid to diagnosis and management of disease. The prospects for nanotechnology and nano-sized analyzers are seemingly limitless, and this field is moving quickly. My future research is directed towards exploring the potential role of nanotechnology in the analytical sciences, and in clinical laboratory science in particular, and identifying useful and worthwhile applications.

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