Analytical Biochemistry

Analytical biochemistry encompasses the suite of chemical and instrumental methods designed to identify, quantify and characterise biomolecules in complex matrices. Central goals include determining concentrations of metabolites, peptides, proteins and nucleic acids; resolving molecular isoforms; mapping spatial or temporal distributions; and monitoring dynamic biochemical processes. Key approaches combine sample‐preparation strategies—such as microsampling, solid‐phase extraction and fractionation—with separation techniques (liquid chromatography, capillary electrophoresis, ultracentrifugation) and detectors offering molecular specificity (mass spectrometry, fluorescence, electrochemical, immuno‐based assays). Recent advances in miniaturisation, microfluidics and high-throughput instrumentation have driven higher sensitivity, faster turnaround and lower sample consumption. Analytical biochemistry underpins modern diagnostics, pharmacokinetics, environmental monitoring and systems‐level ’omics’ studies, enabling the translation of molecular measurements into clinical and biological insights.

Research from Nature Portfolio

Multi-omics microsampling has demonstrated the feasibility of analysing thousands of metabolites, lipids, cytokines and proteins from 10 μL of capillary blood collected serially, paired with wearable sensor data. This platform revealed individualised responses to dietary interventions and charted intra-day molecular fluctuations, laying the groundwork for dynamic health profiling and real-time therapeutic monitoring.

Innovations in high-resolution separations have addressed the purity assessment of long synthetic RNAs, such as 100-nucleotide single-guide RNAs. A comparison of high-temperature ion-pair reversed-phase chromatography with denaturing ion-exchange demonstrated the latter’s superior resolving power and on-column stability, establishing protocols to evaluate RNA integrity across diverse lengths and backbone chemistries.

High-content proteomic analysis of dried blood samples has been enabled by a novel volumetric sampler coupled to quantitative antibody arrays. This workflow facilitated simultaneous measurement of 1 000 proteins from a single DBS, overcoming hematocrit and spot heterogeneity issues and establishing a path toward widespread clinical proteome monitoring from minimally invasive micro-samples.

Analytical Biochemistry publication trend

The graph below shows the total number of articles in analytical biochemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Microsampling: Collection of minute sample volumes (≤ 10 μL) for biochemical analysis, often via capillary blood spots or microdialysis probes.

Ion‐pair reversed‐phase chromatography (IP-RP): A liquid chromatographic mode employing an ionic pairing agent in the mobile phase to retain charged analytes on a hydrophobic stationary phase.

Denaturing ion-exchange chromatography: Separation of biomolecules under basic or chaotropic conditions to unfold macromolecules and exploit charge differences.

Volumetric absorptive microsampling (VAMS): A method that collects a fixed volume of fluid by capillary absorption into a calibrated tip, reducing volume‐dependent variability in dried spot assays.

Limit of detection (LOD): The lowest concentration of an analyte that produces a signal distinguishable from background noise, typically defined by a signal‐to‐noise ratio of 3:1.

Diastereomer selectivity: Chromatographic discrimination between non‐mirror‐image stereoisomers, often critical in analyses of phosphorothioate‐modified oligonucleotides.

References

1. Multi-omics microsampling for the profiling of lifestyle-associated changes in health. Nature Biomedical Engineering (2023).
2. HPLC methods for purity evaluation of man-made single-stranded RNAs. Scientific Reports (2019).
3. Dried blood sample analysis by antibody array across the total testing process. Scientific Reports (2021).
4. Development of a Sensitive Electrochemical Enzymatic Reaction-Based Cholesterol Biosensor Using Nano-Sized Carbon Interdigitated Electrodes Decorated with Gold Nanoparticles. Sensors (2017).
5. Investigation of factors influencing the separation of diastereomers of phosphorothioated oligonucleotides. Analytical and Bioanalytical Chemistry (2019).