Scientists Race to Unlock the Ocean’s Tiny Powerhouses With Greener Extraction Methods

The ocean covers roughly seventy percent of our planet’s surface and gave rise to the earliest forms of life on Earth, yet some of its most valuable chemical treasures are too small to see with the naked eye. Marine microalgae, a diverse group of photosynthetic organisms ranging from prokaryotic cyanobacteria to eukaryotic green algae and diatoms, act as microscopic cellular factories that produce an extraordinary portfolio of bioactive compounds. A new review published in the journal Blue Biotechnology by Junhong Xie and Quanyu Zhao of Nanjing Tech University takes stock of how scientists are learning to extract these compounds sustainably, and why the next generation of extraction chemistry could determine whether the promise of blue biotechnology becomes an industrial reality or remains a laboratory curiosity.

The economic stakes are considerable. Polysaccharides, proteins, lipids, pigments, and polyphenols harvested from marine microalgae have been shown to exhibit anti-inflammatory, antimicrobial, and antitumor activities, while pigments and unsaturated fatty acids contribute antioxidant properties and help meet human nutritional needs. Among the most commercially significant are omega-3 polyunsaturated fatty acids, a market valued at 2.3 billion US dollars in 2019 and expected to grow at an annual rate of 7.44 percent through 2027, with microalgae-derived omega-3 products growing even faster at 11.9 percent per year. High-value pigments such as lutein, beta-carotene, astaxanthin, and fucoxanthin command premium prices as natural food colorants, dietary supplements, and nutraceutical ingredients, and compounds like the polysaccharide chrysolaminarin and beta-glucan add further value to algal biomass.

There is also a pressing environmental driver behind the shift toward microalgal sources. The human body cannot synthesize the omega-3 fatty acids eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA, and must obtain them through diet. Traditionally these have come from fish, but overfishing has disrupted marine ecological balance, and contamination incidents have raised safety concerns about seafood products. Deep-sea fish extraction suffers from poor product stability and off-flavors, while bioaccumulation concentrates pollutants such as methylmercury, copper, polychlorinated biphenyls, and dioxins in fish bodies. Microalgae sidestep many of these problems: species such as Nannochloropsis can synthesize EPA efficiently through photosynthetic autotrophy, with the fatty acid accounting for twenty to thirty percent of total cellular lipids, and their oils are odorless, cholesterol-free, and contain squalene and phytosterols with additional health benefits.

Yet the path from algal pond to finished product is obstructed by a formidable biological barrier: the cell wall. Despite their tiny size, microalgae possess complex polysaccharide-protein composite cell walls whose high mechanical strength causes low energy efficiency and incomplete extraction with conventional disruption methods, and the variability among species means no single approach works universally. Without proper pretreatment, extraction efficiency is severely limited. The review catalogs the main pretreatment strategies in detail, dividing them into mechanical methods, including high-pressure homogenization, ultrasonication, microwave treatment, and pulsed electric fields, and chemical methods such as acid hydrolysis, surfactant treatment, and enzymatic hydrolysis. Drying itself is a pretreatment decision, with freeze-dried samples of species like Chlorella variabilis and Scenedesmus regularis typically showing higher extraction efficiency than spray-dried material, though sun drying remains the cheapest option for large volumes.

The numbers illustrate how difficult cell disruption can be. High-pressure homogenization, one of the few techniques scalable to industrial volumes, achieves only a forty percent lysis rate for Nannochloropsis even at pressures up to 900 bar. Ball milling, which uses friction and collision between microspheres to shatter cell walls, requires careful temperature control because frictional heat can inactivate delicate products; optimized conditions for the lipid-rich organism Schizochytrium sp. DT3 used beads of 0.4 to 0.6 micrometers at 4500 rpm for just four minutes. Enzymatic pretreatment offers a gentler alternative, as enzyme preparations selectively hydrolyze cell wall structures, avoid equipment corrosion, reduce energy consumption, and protect heat-sensitive compounds in a mild aqueous environment. The evidence is striking: combining the enzymes Cellulyve and Feedlyve GMA increased oil extraction from Microcystis by nearly 1.8 times, while a crude mixture of cellulase and amylase doubled protein extraction and boosted sugar extraction by 41 percent in Oocystis sp. The catch is cost, since enzyme preparations are expensive, must be matched precisely to each species’ cell wall chemistry, and demand strict control of reaction parameters.

Once cells are opened, the choice of solvent becomes the next critical decision, and this is where the green chemistry revolution is most visible. Traditional extractions rely on solvents such as chloroform, methanol, and hexane, which are volatile, flammable, explosive, or toxic. The review highlights two leading alternatives. Ionic liquids, composed entirely of cations and anions, feature low vapor pressure, high solvating power, and excellent chemical and thermal stability, and their polarity, hydrophobicity, and viscosity can be tuned by pairing different ions. Researchers evaluated fifteen cholinium and amino acid-based ionic liquids for disrupting the hydrogen-bond network of Nannochloropsis cell walls and found that cholinium arginate performed best, likely because it offers six hydrogen bonding sites. Pairing hydrophilic ionic liquids with microwave assistance increased lipid yield from Nannochloropsis oculata by 34.9 percent compared with the classic Bligh-Dyer chloroform-methanol method, and, importantly, worked on wet algae, eliminating the energy-intensive drying step.

Deep eutectic solvents, or DES, represent an even newer class of green solvents. These form when hydrogen bond acceptors such as choline chloride combine with hydrogen bond donors such as urea or lactic acid to create low-melting mixtures that are biodegradable, easy to synthesize, non-volatile, and non-flammable. Their natural variants, nDES, offer food-grade safety, meaning extracts can be used directly in food systems without solvent purification, a significant simplification of production. Responsive DES go further, allowing solvent polarity to be reversed on demand through external triggers such as pH or temperature, solving the persistent problem of separating target products from solvent. The review also covers supercritical fluid extraction, in which carbon dioxide above its critical point acts as a non-toxic solvent at near-ambient temperature, and pressurized liquid extraction, which cuts processing time by more than half while slashing solvent consumption; one PLE protocol with dimethyl sulfoxide at 103.4 bar recovered lutein, beta-carotene, fucoxanthin, and diatoxanthin from algal biomass in a single pass.

Physical intensification methods can be coupled with these solvent systems to dramatic effect. Microwave technology exploits electromagnetic energy in the 0.3 to 300 gigahertz band to rapidly heat and rupture cells, with optimized conditions of 1.47 minutes of treatment yielding efficient lutein extraction from Chlorella sorokiniana. Ultrasound generates cavitation, microfluidics, and bubble collapse that tear cell walls apart; freezing and thawing combined with ultrasonication pushed C-phycocyanin yield to 109.57 milligrams per gram, well above either technique alone and with the highest purity. A triphasic separation strategy applied to wet marine Chlorella sp. NITT 02 used ultrasonication followed by ammonium sulfate and tert-butanol to split biomass into an oil layer, a protein layer, and a sugar-containing salt layer in one operation. However, the review is candid that green extraction remains difficult: ethanol is less toxic than methanol or chloroform but delivers lower yields, and microwave and ultrasound processes are energy-intensive or limited in scale.

Economics ultimately decide which technologies survive, and here the authors turn to life cycle assessment, a four-step framework covering goal definition, inventory analysis, impact assessment, and interpretation. The figures are sobering: freeze-drying consumes about 1080 megajoules, ultrasonic disruption 108 to 324 megajoules, and solvent recovery 210 to 588 megajoules, while harvesting costs a mere 0.02 megajoules. A multi-product roadmap for marine Chlorella variabilis showed sugar extraction as the most energy-hungry step at 160.8 megajoules per kilogram, compared with just 5.9 for lipid extraction and 5.2 for harvesting. The authors argue that complete separation of every component is unnecessary; extracting only the highest-value products and converting residues through fermentation or thermal conversion achieves better economics, and integrating cultivation with wastewater treatment further improves sustainability.

Perhaps the most forward-looking section of the review concerns artificial intelligence and computational screening. Extraction obeys thermodynamic principles, but phase equilibrium data for multi-component systems containing salts, ionic liquids, and polymers remain scarce, making solvent selection largely empirical. Theoretical tools such as COSMO-RS have guided the design of solvents for extracting lutein, phycobiliproteins, EPA, fucoxanthin, and lipids, with researchers screening databases of roughly 8,000 molecules and narrowing thousands of candidate deep eutectic solvents down to 712 using constraints on boiling point, melting point, greenness, and solubility. Machine learning applied to the wealth of existing laboratory data promises to close the loop between experimental science, theoretical calculation, and AI analysis, accelerating solvent discovery. The authors identify three priorities for the field: standardized pilot-scale extraction test suites, quantified solvent life-cycle impacts, and open databases of extraction yields for machine learning training. If those pieces fall into place, the green extraction of marine microalgal compounds could finally deliver on the promise of blue biotechnology at industrial scale, turning sunlight, seawater, and carbon dioxide into medicines, supplements, and sustainable materials.

Subject of Research: Green extraction of bioactive compounds from marine microalgae

Article Title: Green extraction of active compounds in marine microalgae

Article References: Green extraction of active compounds in marine microalgae. (n.d.). https://doi.org/10.1186/s44315-025-00051-9

Image Credits: AI Generated

DOI: 10.1186/s44315-025-00051-9

Keywords: marine microalgae, green extraction, ionic liquids, deep eutectic solvents, supercritical CO2, pressurized liquid extraction, cell disruption, omega-3 fatty acids, bioactive compounds, blue biotechnology, life cycle assessment, machine learning